Myotonia congenita is a hereditary skeletal muscle channelopathy caused by mutations in the voltage-gated chloride channel (CLCN1) gene, resulting in impaired muscle relaxation after voluntary contraction.

Exam domain	One-glance essentials
Definition / diagnosis	Non-dystrophic hereditary myotonia from CLCN1 chloride-channel loss of function ^[1] Thomsen is AD/milder; Becker is AR/more severe with transient weakness ^[1]
Epidemiology / risks	Genetic disease presenting from childhood; cold and sudden movement worsen stiffness ^[1] Family history may show dominant Thomsen or recessive Becker inheritance ^[1]
Core mechanism	Reduced skeletal-muscle Cl⁻ conductance → membrane hyperexcitability and repetitive action potentials ^[1] Result is delayed relaxation after voluntary contraction, not dystrophic weakness ^[1]
Clinical picture	Stiffness, grip/percussion/eyelid myotonia and often a hypertrophic “Herculean” build ^[1]^[2] Warm-up phenomenon: repeated contraction improves myotonia ^[1] No cataract, cardiac, endocrine or cognitive multisystem syndrome ^[2]
Investigations	EMG: waxing/waning myotonic discharges with otherwise non-dystrophic pattern ^[1] CK normal or mildly raised; NCS normal; check TFT for pseudomyotonia ^[1]^[3] Confirm with CLCN1 genetic testing ^[1]
Management	First-line: warm-up technique, cold avoidance and physiotherapy ^[1]^[3] Mexiletine is usual first-line drug; obtain baseline ECG and monitor conduction ^[1] Lamotrigine is an alternative; provide genetic counselling ^[1]
Complications	Falls, injury and functional limitation; Becker disease may cause transient weakness ^[1] The major preventable danger is succinylcholine-triggered generalised myotonic rigidity ^[1]
Prevention / follow-up	Avoid cold and provoking drugs; use pre-activity warm-up ^[1] Carry anaesthetic/medical-alert information and counsel relatives about inheritance ^[1]
Exam traps	Warm-up = myotonia congenita; paradoxical worsening = paramyotonia congenita ^[1] Multisystem features point to myotonic dystrophy, not myotonia congenita ^[2] It is not malignant hyperthermia; nevertheless succinylcholine is contraindicated ^[1]

References

^[1] Senior notes: Ryan Ho Neurology.pdf (pp. 193–194, Non-dystrophic Myotonic Syndromes) ^[2] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 145, Myotonic Dystrophy and Causes of Myotonia) ^[3] Senior notes: Maksim Medicine Notes.pdf (p. 276, Myopathy Management)

Myotonia Congenita

Myotonia congenita (MC) is a non-dystrophic myotonic disorder — an inherited skeletal muscle channelopathy caused by loss-of-function mutations in the CLCN1 gene encoding the voltage-gated chloride channel (ClC-1) of skeletal muscle. The cardinal feature is myotonia: a delayed relaxation of skeletal muscle after voluntary contraction or mechanical/electrical stimulation, resulting in muscle stiffness.

Let's break down the name:

"Myo-" = muscle (Greek mys)
"-tonia" = tone/tension (Greek tonos)
"Congenita" = present from birth (Latin congenitus)

So the name tells you: muscle stiffness that is present from birth (or early life).

Key Conceptual Distinction — Myotonia vs Dystrophy

Myotonia congenita is a non-dystrophic myotonia. This means the muscle fibres are NOT progressively degenerating (unlike myotonic dystrophy). The problem is purely one of ion channel dysfunction → abnormal electrical excitability → delayed relaxation. The muscle itself is structurally intact and may even be hypertrophied ("Herculean" appearance). This is fundamentally different from myotonic dystrophy (DM1/DM2), which is a trinucleotide repeat disorder with progressive muscle wasting AND multisystem involvement ^[1]^[2].

Myotonia: delayed muscle relaxation after contraction ^[2]

Causes: myotonic dystrophy, myotonia congenita, paramyotonia congenita, proximal myotonic myopathy ^[2]

Prevalence: approximately 1 in 100,000 worldwide, though estimates vary (some Scandinavian populations report higher prevalence up to 1 in 10,000 due to founder effects).
No strong sex predilection overall, but:
- Thomsen disease (autosomal dominant, AD): affects males and females equally.
- Becker disease (autosomal recessive, AR): more clinically apparent in males; females may be carriers or have milder symptoms due to variable expressivity.
Age of onset:
- Thomsen: typically presents in infancy or early childhood (often noted when a toddler has difficulty releasing grip or falls due to stiff legs).
- Becker: onset usually in later childhood to early adolescence (5–12 years), and tends to be more severe despite its later onset.

Myotonia congenita: AD/AR inheritance, due to voltage-gated Cl⁻ channel mutation (7q35) ^[2]

S/S: infancy/childhood onset, generalized myotonia which ↑ in cold and ↓ by warmth/exercise, minimal weakness ^[2]

In Hong Kong, myotonia congenita is rare but recognized. Genetic testing is increasingly available through clinical genetics services at QMH and the HKU Department of Paediatrics/Medicine. The AR (Becker) form is more common globally and is the more clinically significant variant.

3. Anatomy and Function: The Skeletal Muscle Chloride Channel

To understand why a chloride channel defect causes myotonia, you need to understand normal muscle electrophysiology from first principles:

Resting membrane potential of skeletal muscle is approximately –80 to –90 mV.
This resting potential is maintained by:
- K⁺ leak channels (major contributor — K⁺ flows out, making inside negative)
- Chloride channels (ClC-1) — these contribute approximately 70–80% of the resting membrane conductance of skeletal muscle.
When a motor neuron fires, acetylcholine is released at the neuromuscular junction → nicotinic receptors activate → Na⁺ influx → depolarization → action potential propagates along the sarcolemma and into T-tubules → voltage-gated Ca²⁺ channels (dihydropyridine receptors) activate → ryanodine receptors on SR release Ca²⁺ → actin-myosin cross-bridge cycling → contraction.
Relaxation requires:
- Ca²⁺ reuptake into SR (via SERCA pumps)
- Repolarization of the membrane back to resting potential — this is where ClC-1 is critical.

Gene: CLCN1, located on chromosome 7q34-35
Protein: ClC-1, a voltage-gated chloride channel
Structure: functions as a homodimer, with each subunit having its own pore (a "double-barrelled" channel)
Location: densely expressed on the sarcolemma of skeletal muscle fibres
Function: Cl⁻ conductance stabilizes the resting membrane potential. After an action potential, chloride conductance rapidly brings the membrane back towards the resting potential, preventing re-firing.

Why is ClC-1 so important? Because in skeletal muscle (unlike nerve or cardiac muscle), the T-tubule system is extensive and K⁺ can accumulate in the narrow T-tubular lumen during repetitive firing. Without the massive Cl⁻ conductance to "clamp" the membrane near rest, accumulated K⁺ would depolarize the membrane enough to trigger more action potentials. ClC-1 essentially acts as an electrical brake.

4. Etiology and Pathophysiology

Myotonia congenita is caused by loss-of-function mutations in the CLCN1 gene (chromosome 7q34-35). Over 300 different mutations have been identified (missense, nonsense, splice-site, frameshift, deletions).

Two classical forms are recognized based on inheritance pattern:

Feature	Thomsen Disease	Becker Disease
Inheritance	Autosomal dominant (AD)	Autosomal recessive (AR)
First described	Julius Thomsen, 1876 (described in his own family)	Peter Emil Becker, 1977
Prevalence	Rarer	More common (3–10× more prevalent)
Age of onset	Infancy/early childhood	Later childhood/adolescence
Severity	Milder	More severe
Transient weakness	Absent or rare	Present (characteristic)
Muscle hypertrophy	Common	Very common ("Herculean" build)

Don't Confuse Becker Myotonia Congenita with Becker Muscular Dystrophy

These are completely different diseases by different Dr. Beckers. Becker myotonia congenita = AR chloride channelopathy with myotonia and no dystrophy. Becker muscular dystrophy (BMD) = X-linked dystrophinopathy with progressive muscle weakness and wasting. The only thing they share is a surname.

4.2 Pathophysiology — From Ion Channel to Symptom

This is the core concept and is best understood step by step:

Mutations in CLCN1 → reduced or absent functional ClC-1 channels on the sarcolemma
Resting chloride conductance drops from ~80% to < 20% of total membrane conductance

Without ClC-1 to stabilize resting potential, the membrane becomes hyperexcitable
After a normal action potential, instead of cleanly repolarizing, the membrane hovers near threshold
Small depolarizing stimuli (e.g., K⁺ accumulation in T-tubules during repeated firing) now trigger repetitive, self-sustaining action potentials that the muscle fibre cannot shut off

These repetitive action potentials cause sustained muscle contraction = myotonia
The muscle contracts normally but relaxes abnormally slowly because the electrical activity persists long after voluntary drive has ceased
This is why patients describe "stiffness" — the muscle stays contracted for seconds after they try to relax

Mutations in ion channels → leaky channels → failure to maintain stable resting action potential ^[2]

Minor leakage (10-15mV) → myotonia ^[2]

Major leakage (20-30mV) → periodic paralysis ^[2]

High Yield: Pathophysiology Framework for Channelopathies

The GC lecture and senior notes ^[1]^[2] present a unifying framework:

Chloride channel (ClC-1) mutations → myotonia congenita (minor membrane instability → repetitive firing → stiffness)
Sodium channel (SCN4A) mutations → paramyotonia congenita and hyperkalemic periodic paralysis (depending on severity of leak)
Calcium channel (CACNA1S) mutations → hypokalemic periodic paralysis, malignant hyperthermia

The key principle: small leaks cause myotonia; large leaks cause paralysis (because massive depolarization inactivates Na⁺ channels → the fibre becomes completely inexcitable → flaccid weakness).

A hallmark of myotonia congenita (especially Thomsen type) is that myotonia improves with repeated muscle use — this is the "warm-up" phenomenon.
Why? With repeated contractions, there is gradual partial inactivation of Na⁺ channels and some adaptive membrane stabilization. Additionally, increased muscle blood flow washes out accumulated K⁺ from T-tubules. The net effect is that after a few contractions, subsequent ones are smoother and less stiff.
This is opposite to paramyotonia congenita, where myotonia worsens with exercise ("paradoxical myotonia" — hence the name "para-myotonia").

Features [of myotonia]: ^[2]

Painless

Often temperature related (↑ when cold)

Warming-up/down phenomenon (↓ by repeated muscle contraction)

In the AR (Becker) form, the loss of chloride conductance is more severe
At the start of activity, the intense burst of repetitive action potentials can partially depolarize the membrane to a level that inactivates some Na⁺ channels
This transient Na⁺ channel inactivation produces brief weakness at the onset of movement (lasting seconds to minutes) before the warm-up phenomenon kicks in
This transient weakness is NOT seen (or is very mild) in the AD (Thomsen) form

Chronic repetitive involuntary muscle fibre activation acts as a form of isometric exercise
Over time, muscle fibres hypertrophy → patients may have an impressively muscular ("Herculean") build, especially in the legs, buttocks, and shoulders
This is paradoxical: the patient looks strong but complains of stiffness

Thomsen (AD): The mutant ClC-1 subunit exerts a dominant-negative effect. Since ClC-1 functions as a homodimer, one mutant subunit can impair the function of the dimer even when paired with a normal subunit. However, enough functional channels remain → milder phenotype.
Becker (AR): Both alleles carry loss-of-function mutations → near-complete loss of ClC-1 function → more severe myotonia + transient weakness.

Myotonia congenita is classified within the broader category of hereditary myotonias (non-dystrophic myotonias):

Important examples [of ion channelopathies]: ^[2]

Cl⁻ channel: myotonia congenita

Na⁺ channel: paramyotonia congenita, hyperkalemic (K⁺ sensitive) periodic paralysis

Ca²⁺ channel: hypokalemic periodic paralysis, malignant hyperthermia

Muscular dystrophies [GC 056 classification]: ^[1]

Duchenne (DMD), Becker (BMD)

Facioscapulohumeral (FSHD)

Limb-girdle (LGMD)

Myotonic dystrophy (MyoD)

Classification Context from GC 056

The GC lecture slide on muscular dystrophies ^[1] lists myotonic dystrophy (MyoD) under the dystrophic category. Myotonia congenita is distinct — it is a non-dystrophic myotonia. Both share the symptom of myotonia but differ fundamentally: MC has no progressive muscle degeneration and no multisystem involvement.

6. Clinical Features

Symptom	Pathophysiological Basis
Muscle stiffness (myotonia) — the cardinal symptom. Patients say "my muscles lock up" or "I can't let go." Worse in hands, legs, and eyelids.	Loss of Cl⁻ conductance → membrane hyperexcitability → repetitive action potentials → sustained involuntary contraction → delayed relaxation
"Warm-up" phenomenon — stiffness improves with repeated movement. "The first few steps are stiff, but then I loosen up."	Repeated contractions → gradual Na⁺ channel inactivation + K⁺ washout from T-tubules → membrane stabilizes → myotonia diminishes
Worsening with cold — patients report stiffness is much worse in cold weather or after cold exposure	Cold slows Cl⁻ channel kinetics further (already reduced) and enhances Na⁺ channel recovery from inactivation → net effect is more repetitive firing → worse myotonia
Worsening after prolonged rest — "First movement of the morning is the worst"	After rest, no warm-up effect; K⁺ may accumulate in T-tubules; first contraction meets a fully hyperexcitable membrane
Transient weakness at onset of movement (mainly Becker form) — brief weakness (seconds) before warm-up kicks in	Severe Cl⁻ loss → massive initial depolarization → partial Na⁺ channel inactivation → transient inexcitability → weakness; then warm-up gradually restores function
Difficulty with sudden movements — e.g., cannot quickly stand up, catch a ball, or start running; risk of falling	Myotonia locks muscles at initiation of movement; voluntary force is generated but relaxation lag means antagonist muscles resist
Difficulty releasing grip — classic complaint (e.g., shaking hands, opening jar)	Hand intrinsic muscles stay contracted after gripping; repeated opening/closing improves (warm-up)
Eyelid stiffness / inability to open eyes quickly after forced closure	Orbicularis oculi myotonia → delayed lid opening

High Yield Clinical Pearl: Stiffness, Not Weakness

In myotonia congenita, the chief complaint is stiffness, NOT weakness. Strength is generally normal or even above average (due to muscle hypertrophy). The transient weakness in Becker MC is brief and at the onset of movement only. If a patient has myotonia WITH progressive weakness AND multisystem features, think myotonic dystrophy instead.

Sign	How to Elicit	Pathophysiological Basis
Grip myotonia	Ask patient to grip your fingers tightly for 5 seconds, then release. Observe delayed opening of the hand.	Sustained involuntary contraction of finger flexors due to repetitive muscle action potentials
Percussion myotonia	Tap the thenar eminence briskly with a tendon hammer. A sustained dimple/contraction appears and slowly relaxes over several seconds.	Direct mechanical stimulation triggers action potentials in hyperexcitable muscle → sustained contraction
Eyelid myotonia ("lid-lag" variant)	Ask patient to look up, then quickly look down. The upper lid lags or the patient cannot open eyes quickly after forceful closure.	Myotonia of levator palpebrae superioris or orbicularis oculi
Muscle hypertrophy ("Herculean" or "athletic" build)	Inspect. Particularly prominent in calves, thighs, buttocks, shoulders, forearms.	Chronic involuntary isometric exercise of hyper-excitable fibres → work hypertrophy
Normal or near-normal muscle strength on formal testing	Standard MRC grading of muscle power	Unlike dystrophies, the contractile apparatus is intact; the problem is purely electrical
Normal deep tendon reflexes	Standard reflex testing	Lower motor neuron arc is intact; muscle itself is intact
No muscle wasting	Inspect	No degeneration/necrosis of fibres; in fact, fibres are hypertrophied
No multisystem signs (no cataracts, no cardiac conduction defects, no endocrinopathy, no cognitive impairment)	General examination	This distinguishes MC from myotonic dystrophy, which is a multisystem disease

Clinical tests [for myotonia]: ^[2] — percussion myotonia, grip myotonia, eyelid myotonia

Warm-Up Phenomenon — The Clinical Test

To demonstrate the warm-up phenomenon at the bedside:

Ask the patient to make a fist and release — the first release is slow (myotonia).
Ask them to repeat this 5–10 times rapidly.
By the 5th–10th repetition, the release is noticeably faster/smoother. This is pathognomonic for chloride channel myotonia (MC) and helps distinguish it from paramyotonia congenita (where repeated contractions make myotonia worse).

Feature	Myotonia Congenita	Paramyotonia Congenita	Myotonic Dystrophy (DM1)
Channel	Cl⁻ (ClC-1)	Na⁺ (Nav1.4)	RNA toxicity (CTG repeat)
Gene	CLCN1 (7q35)	SCN4A (17q23)	DMPK (19q13.3)
Inheritance	AD (Thomsen) or AR (Becker)	AD	AD (with anticipation)
Onset	Infancy–childhood	Infancy	15–40 years
Warm-up	Yes (myotonia improves with repeated use)	No — paradoxical (worsens with use)	Variable (may have some warm-up)
Cold sensitivity	Yes (worsens)	Yes (markedly worsens, triggers episodes)	Mild
Weakness	Minimal (transient in Becker)	Yes (can be prolonged after cold exposure)	Progressive, distal > proximal
Muscle wasting	No (hypertrophy instead)	No	Yes (temporal, sternomastoid, distal limb)
Multisystem	No	No	Yes (cataracts, cardiac, DM, gonadal, cognitive)
EMG	Myotonic discharges	Myotonic discharges + decremental CMAP with cooling	Myotonic discharges

Myotonic dystrophy (MyD) ^[2]:

Cause: CTG expansion at 19q13.3, AD inheritance

Weakness + wasting in distal muscles, temporalis, sternomastoid, facial and jaw muscles

Myotonia

Multisystem involvement incl. Eyes: cataract; Cardiac: cardiomyopathy, conduction disorders; Endocrinopathy: DM, testicular atrophy; Smooth muscle disorder; Cognitive dysfunction

Characteristic myotonic facies

High Yield: Why Distinguish MC from Myotonic Dystrophy?

This is a common exam question. The key differentiators:

MC: stiffness WITHOUT weakness, NO wasting, NO multisystem features, warm-up phenomenon present, muscle hypertrophy, benign prognosis.
Myotonic dystrophy: stiffness WITH progressive weakness + wasting + cataracts + cardiac conduction defects + endocrinopathy + cognitive dysfunction + characteristic facies (hollow temples, ptosis, long face). Progressive and potentially life-threatening (cardiac arrhythmias, respiratory failure).

High Yield Summary

Myotonia Congenita — Key Points for Exams:

Definition: Non-dystrophic hereditary myotonia due to loss-of-function mutations in CLCN1 (voltage-gated Cl⁻ channel, chromosome 7q35).
Two forms: Thomsen (AD, milder, earlier onset) and Becker (AR, more severe, later onset, transient weakness).
Pathophysiology: Reduced Cl⁻ conductance → membrane hyperexcitability → repetitive action potentials → delayed relaxation (myotonia). Minor leakage → myotonia; major leakage → paralysis.
Cardinal symptom: Muscle stiffness (NOT weakness). Strength is preserved or even enhanced (muscle hypertrophy).
Warm-up phenomenon: Myotonia improves with repeated contraction — this distinguishes MC from paramyotonia congenita (where myotonia paradoxically worsens).
Cold worsening: Myotonia increases in cold temperatures.
No multisystem features: Unlike myotonic dystrophy, there are NO cataracts, cardiac conduction defects, endocrinopathy, or cognitive decline.
Signs: Grip myotonia, percussion myotonia, eyelid myotonia, muscle hypertrophy ("Herculean build"), normal reflexes, no wasting.
Prognosis: Generally benign; life expectancy is normal. The stiffness is the main source of disability.
Channelopathy framework: Cl⁻ channel → MC; Na⁺ channel → paramyotonia congenita / hyperK PP; Ca²⁺ channel → hypoK PP / malignant hyperthermia.

Active Recall - Myotonia Congenita

^[1] GC 056. Generalized muscle weakness.pdf (Muscular dystrophies classification slide) ^[2] Ryan Ho Neurology.pdf (pp. 193–194: Myotonic Dystrophy, Ion Channelopathies, Non-dystrophic myotonic syndromes, Periodic paralysis) ^[3] Block A - Inherited Cardiac conditions.pdf (Cardiomyopathy and neuromuscular associations) ^[4] MBBS Final MB (Medicine) (Felix PY Lai).pdf (Periodic paralysis and channelopathies overview)

Differential Diagnosis of Myotonia Congenita

The clinical approach to a patient presenting with myotonia (delayed muscle relaxation after contraction) requires systematic differentiation from conditions that mimic or share this symptom. The DDx also encompasses the broader scenario where a patient presents with muscle stiffness, difficulty releasing grip, or "locking up" of muscles, since these are the presenting complaints that bring a myotonia congenita patient to the clinic.

We will organize this in two tiers:

Differential diagnosis of myotonia (the symptom) — i.e., what else causes delayed muscle relaxation?
Differential diagnosis of muscle stiffness (the broader complaint) — i.e., non-myotonic causes of stiffness that can mimic MC.

Tier 1: Differential Diagnosis of Myotonia (the Symptom)

Causes [of myotonia]: myotonic dystrophy, myotonia congenita, paramyotonia congenita, proximal myotonic myopathy ^[1]^[2]^[3]

These are the conditions where true electrical myotonia exists — i.e., EMG shows myotonic discharges (repetitive, waxing-and-waning discharges with a characteristic "dive-bomber" sound). The key is distinguishing them from each other.

These share the feature of myotonia WITHOUT progressive muscle wasting and WITHOUT multisystem involvement. They differ by the ion channel involved and specific clinical nuances.

Condition	Channel/Gene	Inheritance	Key Distinguishing Features
Myotonia Congenita (Thomsen)	Cl⁻ / CLCN1 (7q35)	AD	Onset infancy; generalized myotonia; warm-up phenomenon; mild; no weakness; muscle hypertrophy
Myotonia Congenita (Becker)	Cl⁻ / CLCN1 (7q35)	AR	Onset later childhood; more severe; transient weakness at onset of movement; marked muscle hypertrophy
Paramyotonia Congenita	Na⁺ / SCN4A (17q23)	AD	Onset infancy; paradoxical myotonia (worsens with repeated use — opposite of warm-up); markedly worsened by cold; associated with flaccid weakness after cold exposure; may overlap with hyperK PP
Sodium Channel Myotonia (myotonia fluctuans, myotonia permanens, acetazolamide-responsive myotonia)	Na⁺ / SCN4A	AD	Variable severity; fluctuating myotonia; may respond to acetazolamide; no periodic paralysis

Myotonia congenita: AD/AR inheritance, due to voltage-gated Cl⁻ channel mutation (7q35) ^[2] S/S: infancy/childhood onset, generalized myotonia which ↑ in cold and ↓ by warmth/exercise, minimal weakness ^[2]

Paramyotonia congenita: AD inheritance, due to voltage-gated Na⁺ channel mutation (17q23) ^[2] S/S: infantile onset, attacks of myotonia which ↑ in cold and hyperK, ↓ by hypoK, a/w flaccid weakness ^[2]

High Yield: Warm-Up vs Paradoxical Myotonia

The single most important clinical test to distinguish myotonia congenita from paramyotonia congenita at the bedside:

MC: Repeated grip → myotonia improves (warm-up phenomenon). This is because repeated use gradually inactivates Na⁺ channels and clears K⁺ from T-tubules.
PMC: Repeated grip → myotonia worsens (paradoxical). This is because the mutant Na⁺ channel in PMC has defective inactivation — more use means more channels stuck open → more depolarization → more myotonia.

The name "para-myotonia" literally means "beyond/against myotonia" — the myotonia behaves opposite to what you'd expect ^[2].

Myotonic dystrophy (MyD): ^[2]^[3]

Incidence: 5/100k births

Cause: CTG expansion at 19q13.3, AD inheritance

S/S: usually onset at 15-40y, slowly progressive

Weakness + wasting in distal muscles, temporalis, sternomastoid, facial and jaw muscles

Myotonia

Multisystem involvement, incl.:

Eyes: cataract

Cardiac: cardiomyopathy, conduction disorders

Endocrinopathy: DM, testicular atrophy

Smooth muscle disorder: e.g. gut motility disorder, constipation, poor bladder emptying

Cognitive dysfunction

Characteristic myotonic facies

Condition	Gene/Mechanism	Inheritance	Key Distinguishing Features from MC
Myotonic Dystrophy Type 1 (DM1) (Steinert disease)	CTG trinucleotide repeat in DMPK (19q13.3)	AD (with anticipation)	Onset 15-40y; progressive distal weakness + wasting (temporalis, sternomastoid, distal limbs); myotonic facies (long, expressionless, ptosis, temporal hollowing); multisystem: cataracts, cardiac conduction defects, DM, testicular atrophy, cognitive decline; frontal balding
Myotonic Dystrophy Type 2 (DM2) (PROMM — Proximal Myotonic Myopathy)	CCTG tetranucleotide repeat in CNBP (3q21)	AD	Onset adulthood; proximal weakness (unlike DM1 which is distal); milder myotonia; similar but generally milder multisystem features; no congenital form

Myotonic dystrophy (AD) [from Maksim notes]: ^[5] Type 1: CTG trinucleotide repeat in DMPK gene Type 2: CCTG tetranucleotide repeat in CNBP gene Distal muscle weakness; Myotonia: hand grip, close eyes, percussion myotonia; Myopathic facies (tented open mouth, elongated face, expressionless); Frontal baldness, temporalis wasting, bilateral ptosis, cataract, cardiomyopathy

The Most Important DDx: MC vs DM1

This is the number one differential to get right. Both have myotonia — but:

Feature	Myotonia Congenita	Myotonic Dystrophy (DM1)
Muscle bulk	Hypertrophied ("Herculean")	Wasted (temporal hollowing, thin sternomastoids)
Weakness	Absent or transient	Progressive, distal
Multisystem	None	Cataracts, cardiac, DM, gonadal, cognitive
Face	Normal	Myopathic facies (long, expressionless, ptosis)
Prognosis	Normal lifespan	Reduced lifespan (cardiac/respiratory)
Genetics	CLCN1 (Cl⁻ channel)	DMPK (CTG repeat, RNA toxicity)

If a patient with myotonia has cataracts or a cardiac conduction defect, it is NOT MC — it is DM1 until proven otherwise.

Some periodic paralyses have inter-ictal myotonia (myotonia between paralytic attacks). These are important to consider because a patient with hyperkalemic periodic paralysis may present with myotonia as the predominant complaint.

Important examples [of ion channelopathies]: ^[2]

Cl⁻ channel: myotonia congenita

Na⁺ channel: paramyotonia congenita, hyperkalemic (K⁺ sensitive) periodic paralysis

Ca²⁺ channel: hypokalemic periodic paralysis, malignant hyperthermia

Condition	Channel/Gene	Key Distinguishing Features
Hyperkalemic Periodic Paralysis	Na⁺ / SCN4A	Episodes of flaccid weakness (minutes to hours) triggered by fasting, K⁺ intake, cold, rest after exercise; inter-ictal myotonia on EMG; onset in first decade; serum K⁺ elevated during attacks
Hypokalemic Periodic Paralysis	Ca²⁺ / CACNA1S (or Na⁺ / SCN4A)	Episodes of flaccid weakness triggered by CHO load, rest after exercise; NO myotonia; serum K⁺ low during attacks

The key distinction: In MC, weakness is absent or very brief and the dominant problem is stiffness. In periodic paralyses, the dominant problem is episodic flaccid weakness, and myotonia (if present) is a secondary feature.

Certain drugs can cause electrical myotonia on EMG or clinical myotonia:

Drug/Toxin	Mechanism
Statins (e.g., simvastatin, atorvastatin)	Membrane destabilization via cholesterol depletion in sarcolemma → altered Cl⁻/Na⁺ channel function
Chloroquine / Hydroxychloroquine	Lysosomal myopathy with secondary myotonic discharges
Colchicine	Myopathy with myotonic discharges
Fibrates (e.g., clofibrate)	Direct sarcolemmal effect
Propranolol (rare)	Na⁺ channel blockade effect
2,4-D herbicide	Chloride channel inhibition

In clinical practice, always take a drug history in any patient presenting with new myotonia. Drug-induced myotonia is an acquired, reversible cause that must be excluded before labelling a condition as inherited.

Hypothyroidism can cause pseudomyotonia — clinically similar to myotonia (slow muscle relaxation) but the EMG shows electrically silent contraction (no myotonic discharges). The mechanism is impaired Ca²⁺ reuptake by SERCA into the SR due to low thyroid hormone → slow cross-bridge uncoupling → slow mechanical relaxation. This is distinct from true myotonia because the problem is mechanical (slow Ca²⁺ handling), not electrical (repetitive action potentials).

The classic sign is delayed relaxation of deep tendon reflexes ("hung-up" reflexes), especially the ankle jerk.
Check TFT in any patient with apparent myotonia to exclude hypothyroidism.

When a patient says "my muscles are stiff," they may not have true myotonia. Other causes of muscle stiffness include:

Condition	Mechanism	Key Distinguishing Features
Stiff-person syndrome (SPS)	Anti-GAD65 antibodies → impaired GABAergic inhibition in spinal cord → continuous motor neuron firing → sustained contraction	Progressive axial stiffness and rigidity; episodic painful spasms triggered by noise/touch; antibodies to GAD65 or amphiphysin; associated with T1DM; EMG shows continuous motor unit activity (NOT myotonic discharges)
Neuromyotonia (Isaacs syndrome)	Anti-CASPR2/LGI1 antibodies (or KCNA1 mutations) → voltage-gated K⁺ channel dysfunction at peripheral nerve → hyperexcitability → continuous muscle fibre activity	Muscle stiffness + visible rippling/myokymia + delayed relaxation; EMG shows neuromyotonic discharges (very high frequency, > 150 Hz, decrementing) rather than myotonic discharges; peripheral nerve origin
Cramp-fasciculation syndrome	Peripheral nerve hyperexcitability	Muscle cramps + fasciculations; stiffness is intermittent and painful (unlike painless myotonia in MC)
Spasticity (UMN lesion)	Loss of descending inhibition → increased tone, velocity-dependent	Clasp-knife pattern; hyperreflexia; Babinski positive; distribution follows UMN pattern; no percussion myotonia
Rigidity (extrapyramidal)	Basal ganglia dysfunction → co-contraction of agonist/antagonist	Lead-pipe or cogwheel; NOT velocity-dependent; associated with bradykinesia/tremor; no myotonic discharges
Contracture (metabolic myopathy, e.g., McArdle disease)	Glycogen storage disease type V → cannot break down glycogen → ATP depletion during exercise → failure of cross-bridge detachment	Muscle stiffness/hardening during exercise; electrically silent on EMG (no action potentials at all — a true contracture, not myotonia); associated with exercise intolerance, myoglobinuria

True Myotonia vs Pseudomyotonia vs Contracture vs Neuromyotonia

Feature	True Myotonia	Pseudomyotonia	Contracture	Neuromyotonia
EMG	Myotonic discharges (waxing/waning, "dive-bomber")	Electrically silent slow relaxation	Electrically silent	Very high-frequency decrementing bursts
Example	MC, DM1, PMC	Hypothyroidism	McArdle disease	Isaacs syndrome
Origin	Muscle membrane (sarcolemma)	Impaired SR Ca²⁺ reuptake	Metabolic (ATP depletion)	Peripheral nerve terminal
Warm-up	Yes (in MC)	No	No (worsens with exercise)	No

This distinction is critical because the approach to investigation and management differs entirely.

Condition	Channel/Cause	Myotonia?	Warm-up?	Weakness?	Multisystem?	Key Distinguisher
Myotonia congenita	Cl⁻ (CLCN1)	Yes	Yes	Minimal/transient	No	Muscle hypertrophy, benign
Paramyotonia congenita	Na⁺ (SCN4A)	Yes	Paradoxical	Yes (cold-induced)	No	Worsens with cold AND exercise
HyperK periodic paralysis	Na⁺ (SCN4A)	Yes (inter-ictal)	Variable	Episodic flaccid	No	K⁺ elevated during attacks
DM1	CTG repeat (DMPK)	Yes	Variable	Progressive distal	Yes	Facies, cataracts, cardiac, cognitive
DM2 (PROMM)	CCTG repeat (CNBP)	Yes (milder)	Variable	Proximal	Yes (milder)	Proximal weakness pattern
Hypothyroidism	Impaired SERCA	Pseudomyotonia	No	Proximal	Yes (systemic)	Slow reflexes, electrically silent, ↑TSH
McArdle disease	Myophosphorylase deficiency	No (contracture)	No	Exercise-related	No	Electrically silent; second-wind phenomenon
Neuromyotonia	VGKC antibodies	No (neuromyotonic)	No	Variable	May have (Morvan)	Myokymia, rippling; peripheral nerve origin
Drug-induced	Various	Yes/pseudo	No	Variable	No	Drug history! Reversible on cessation

When you see a patient with apparent myotonia, the clinical reasoning proceeds as follows:

Confirm true myotonia — percussion myotonia, grip myotonia, EMG confirmation (myotonic discharges with waxing/waning amplitude and frequency).
Exclude acquired/drug causes — drug history (statins, chloroquine), TFTs (hypothyroidism).
Assess for dystrophic features — any weakness? Wasting? Cataracts (slit-lamp)? Cardiac conduction abnormalities (ECG)? Endocrinopathy? Cognitive change? If yes → myotonic dystrophy.
Characterize the myotonia — does it warm up (MC) or paradoxically worsen (PMC)? Is it predominantly cold-triggered with subsequent weakness (PMC)?
Assess for episodic paralysis — if present, think periodic paralysis with myotonia (hyperK PP).
Confirm with genetic testing — CLCN1 for MC, SCN4A for PMC/hyperK PP, DMPK/CNBP for DM1/DM2.

Muscular dystrophies [from GC 056 classification]: ^[4] Duchenne (DMD), Becker (BMD); Facioscapulohumeral (FSHD); Limb-girdle (LGMD); Myotonic dystrophy (MyoD)

Note: the muscular dystrophies listed in the GC 056 slide ^[4] are differential diagnoses in the sense that myotonic dystrophy (MyoD) is the dystrophic condition that must be excluded when evaluating a patient with myotonia. The other dystrophies (DMD, BMD, FSHD, LGMD) do NOT have myotonia and present primarily with progressive weakness — they enter the DDx only if the chief complaint is "weakness" rather than "stiffness."

Differential Diagnosis of Myopathy [from medicine neurology lecture]: ^[6] Infective: Viral (HIV, CMV, EBV...), pyomyositis Neoplastic: Paraneoplastic Inflammatory: Rheumatoid arthritis, Sjögren's syndrome Congenital: Muscular dystrophy Autoimmune: Dermatomyositis, necrotising autoimmune myositis Trauma/toxin: Crush injuries/seizures causing rhabdomyolysis, glucocorticoids, colchicine, statins Endocrine: Hypothyroidism, Cushing's syndrome, hypokalemia

These are the broad DDx for myopathy (weakness). Most of these do NOT cause myotonia and are therefore distinguished from MC by the absence of grip/percussion myotonia and the presence of progressive weakness. They are relevant mainly when the clinician is casting a wide net for "what is wrong with this patient's muscles?"

High Yield Summary — DDx of Myotonia Congenita

Always confirm true myotonia (EMG myotonic discharges) — exclude pseudomyotonia (hypothyroidism), contracture (McArdle), and neuromyotonia (Isaacs).
The #1 DDx is myotonic dystrophy (DM1 > DM2) — look for progressive weakness, wasting, cataracts, cardiac, endocrine, and cognitive features. If ANY of these are present, it is NOT MC.
Among non-dystrophic myotonias, the main DDx is paramyotonia congenita — distinguished by paradoxical myotonia (worsens with use) and Na⁺ channel gene (SCN4A).
HyperK periodic paralysis can have inter-ictal myotonia but is distinguished by episodic flaccid weakness with elevated K⁺.
Drug-induced myotonia (statins, chloroquine) is acquired and reversible — always take a drug history.
Warm-up phenomenon = MC; paradoxical worsening = PMC — this is the bedside differentiator.

Active Recall - DDx of Myotonia Congenita

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 145: Myotonic Dystrophy, causes of myotonia) ^[2] Senior notes: Ryan Ho Neurology.pdf (pp. 193–194: Ion channelopathies, non-dystrophic myotonic syndromes, periodic paralysis) ^[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 706: Differential diagnosis of myopathies) ^[4] Lecture slides: GC 056. Generalized muscle weakness.pdf (Muscular dystrophies classification slide) ^[5] Senior notes: Maksim Medicine Notes.pdf (p. 276: Myopathy approach, myotonic dystrophy features) ^[6] Lecture slides: Neurology - Two cases of lower limb weakness.pdf (p. 38: Differential diagnosis of myopathy)

Diagnosis of Myotonia Congenita: Criteria, Algorithm, and Investigations

There are no universally codified "diagnostic criteria" for myotonia congenita in the way that, say, the Jones criteria exist for rheumatic fever. Instead, the diagnosis is reached through a clinical-electrophysiological-genetic triad. In practice, a confident diagnosis of MC requires:

Component	Requirement
1. Clinical	History of painless muscle stiffness (myotonia) from infancy or childhood, with warm-up phenomenon, no progressive weakness, no multisystem features, ± family history consistent with AD or AR inheritance
2. Electrophysiological	EMG demonstrating myotonic discharges — the hallmark waxing-and-waning, high-frequency repetitive discharges with the characteristic "dive-bomber" sound; normal NCS
3. Genetic	Pathogenic mutation identified in CLCN1 (chromosome 7q34-35) on genetic testing — this is the gold standard confirmatory test

All three components reinforce each other, but genetic testing is the definitive confirmation. A patient can be diagnosed clinically + electrophysiologically with high confidence even without genetics, but genetic confirmation is increasingly standard (and essential for genetic counselling and family screening).

High Yield: Why Clinical Alone Is Insufficient

Clinical myotonia alone does NOT make the diagnosis. You must:

Exclude dystrophic myotonia (DM1/DM2) — because both have myotonia, but DM1 has progressive weakness + multisystem involvement and a completely different prognosis.
Exclude paramyotonia congenita — because both are non-dystrophic channelopathies, but PMC involves SCN4A (Na⁺ channel) and may require different management.
Exclude acquired causes — drug-induced myotonia, hypothyroidism.

The EMG and genetic testing provide the specificity needed.

Dx [of myotonic dystrophy]: usually clinical ± genetic testing ^[1]^[3]

This principle applies similarly to MC — clinical suspicion followed by confirmatory genetic testing ^[2].

The following algorithm represents the systematic approach to a patient presenting with the chief complaint of muscle stiffness or delayed relaxation, leading to a diagnosis of myotonia congenita.

3. Investigation Modalities — Detailed Interpretation

These are performed before any laboratory or electrophysiological investigations. They are the first-line screening tools.

Test	Technique	Positive Finding in MC	Pathophysiological Basis
Grip myotonia	Ask patient to make a tight fist for 5 seconds then open quickly	Delayed opening — fingers slowly unfurl over 2–10 seconds; improves on repeated trials (warm-up)	Repetitive action potentials in finger flexors due to reduced Cl⁻ conductance → sustained contraction
Percussion myotonia	Tap thenar eminence sharply with tendon hammer	Sustained dimple or thumb adduction/opposition lasting several seconds before slowly relaxing	Direct mechanical stimulation of hyperexcitable sarcolemma → burst of repetitive APs
Eyelid myotonia	Ask patient to close eyes tightly for 5 seconds, then open	Delayed lid opening; may see a brief scleral flash as the lid slowly retracts	Orbicularis oculi myotonia
Warm-up test	Repeat grip-release 10 times rapidly	Progressively faster release with each repetition	Gradual Na⁺ channel inactivation + K⁺ clearance from T-tubules with repeated use
Cold provocation (optional)	Immerse hand in cold water for 5 minutes, then test grip myotonia	Worsening of myotonia after cold exposure	Cold slows residual Cl⁻ channel kinetics and enhances Na⁺ channel recovery from inactivation → more repetitive firing

Clinical tests [for myotonia]: [grip myotonia, percussion myotonia, eyelid myotonia] ^[1]^[2]

Myotonia: hand grip, close eyes, percussion myotonia ^[5]

Exam Tip: Describing Clinical Tests

For clinical exams (OSCE/long case), when asked to demonstrate myotonia, describe all three tests: grip myotonia, percussion myotonia, and eyelid myotonia. Then specifically demonstrate the warm-up phenomenon by asking the patient to repeat grip-release. State: "Myotonia that improves with repeated contraction is consistent with chloride channel myotonia (myotonia congenita) and argues against paramyotonia congenita."

Investigation	Expected Finding in MC	Why This Test?	Interpretation
Serum CK	Normal or mildly elevated (typically < 2–3× ULN)	CK is released when muscle membranes are damaged. In MC, muscle fibres are NOT degenerating — the architecture is intact. Hence CK is NOT significantly elevated.	CK > 1000 → think inflammatory myopathy, DMD/BMD, rhabdomyolysis ^[3]^[5]. CK 200–1000 → non-specific, can be seen in vigorous exercise, after EMG, or mild myopathy ^[3]. In MC, CK is typically normal to very mildly raised because there is no structural muscle damage — only electrical dysfunction.
Serum electrolytes (K⁺, Na⁺, Ca²⁺, Mg²⁺, PO₄³⁻)	Normal	To exclude electrolyte-mediated muscle dysfunction (hypoK, hyperK) and periodic paralysis	If K⁺ is abnormal, consider periodic paralysis or secondary causes. In MC, electrolytes are normal between and during episodes of stiffness.
Thyroid function tests (TFT)	Normal	To exclude hypothyroid pseudomyotonia and thyrotoxic periodic paralysis	Hypothyroidism causes slow relaxation (pseudomyotonia) that is electrically silent. Hyperthyroidism can cause periodic paralysis (especially in Asian males). Both must be excluded.
Liver function / Renal function	Normal	Baseline; exclude systemic causes of myopathy	Drug-induced or metabolic myopathies may have deranged LFT/RFT.

Investigations [for myopathy]: ^[3]^[7]

CK, ALT, LDH

CK: 200-1000 for most myopathies; > 1000 for inflammatory myopathies, rhabdomyolysis, DMD/BMD

NCS: to rule out neuropathy

EMG: polyphasic, low-amplitude motor unit potential [in myopathy]

Muscle biopsy

Ix for underlying causes

3.3 Electrophysiology — NCS and EMG

This is the most important investigation after clinical assessment. It confirms true electrical myotonia and helps narrow the differential.

Parameter	Expected Finding in MC	Interpretation
Motor NCS	Normal — normal CMAP amplitude, distal latency, conduction velocity	Confirms the pathology is NOT in the peripheral nerve (excludes neuropathy). The motor neuron and axon are intact; the problem is in the muscle membrane itself.
Sensory NCS	Normal	Confirms no sensory nerve involvement (myotonia is a purely motor phenomenon).
F-waves	Normal	Normal proximal conduction.

NCS: to rule out neuropathy (can also cause reduced motor response) ^[5]

This is where the diagnosis is clinched electrophysiologically. EMG in MC shows myotonic discharges — these are the single most important electrophysiological finding.

Feature	Description	Why It Occurs
Myotonic discharges	Repetitive, high-frequency (20–150 Hz) discharges of single muscle fibres that wax and wane in both amplitude and frequency. Produce the characteristic "dive-bomber" sound on the audio speaker.	Each discharge represents a single muscle fibre firing repeatedly due to membrane hyperexcitability from reduced Cl⁻ conductance. The waxing-and-waning pattern reflects the fluctuating membrane potential hovering near threshold — sometimes recruiting more fibres (waxing), sometimes fewer (waning).
Triggered by	Needle insertion (insertional activity), percussion, voluntary contraction, or movement of the needle	Mechanical perturbation of a hyperexcitable membrane triggers a burst of repetitive APs
Distribution	Widespread — found in multiple muscles, both proximal and distal	ClC-1 is expressed throughout skeletal muscle; the defect is generalized
Voluntary MUAPs	Normal morphology — normal amplitude, normal duration, normal recruitment	Unlike myopathy (which has small, short, polyphasic MUAPs) or neuropathy (which has large, long MUAPs with reduced recruitment), MC has structurally normal muscle — the motor units fire normally. The abnormality is the EXTRA involuntary discharges between and after voluntary activation.

High Yield: EMG Pattern Recognition

Condition	EMG Finding	Sound
Myotonia congenita	Myotonic discharges (waxing/waning)	"Dive-bomber"
Myotonic dystrophy	Myotonic discharges + small polyphasic MUAPs (myopathic)	"Dive-bomber" + myopathic units
Paramyotonia congenita	Myotonic discharges ± decremental CMAP with cooling	"Dive-bomber"
Normal myopathy (e.g., polymyositis)	Small, short, polyphasic MUAPs; early recruitment; NO myotonic discharges	No dive-bomber
Neuropathy	Large, long MUAPs; reduced recruitment; fibrillation potentials	No dive-bomber

The presence of myotonic discharges with normal voluntary MUAPs (no myopathic changes) strongly favours a non-dystrophic myotonia (MC or PMC) over myotonic dystrophy ^[2]^[5].

In research centres or specialized neuromuscular clinics, provocative electrophysiological protocols may be used:

Protocol	Technique	Expected Finding in MC
Short exercise test	Brief (10-second) maximal isometric contraction of a muscle (e.g., abductor digiti minimi) with CMAP recording before and after	In MC: transient drop in CMAP amplitude immediately post-exercise (due to myotonia interfering with relaxation), followed by recovery. In Becker MC, there may also be a delayed CMAP decrement (reflecting transient weakness).
Long exercise test	5 minutes of intermittent exercise (5 seconds on, 5 seconds off) with CMAP every minute for 40-50 minutes post-exercise	In MC: typically shows a pattern 3 response (transient CMAP drop with exercise that recovers quickly). In periodic paralysis: prolonged CMAP decrement.
Cooling protocol	Record CMAP/myotonia before and after cooling the limb to 20°C	In MC: increased myotonic discharges with cold. In PMC: dramatic increase in myotonia + CMAP decrement with cold (paradoxical myotonia). This helps differentiate Cl⁻ channelopathies from Na⁺ channelopathies.

These tests are not routine but are helpful when the clinical picture is ambiguous (e.g., overlap between MC and PMC) or when genetic testing is inconclusive.

Genetic testing [for muscle diseases] ^[3]^[7]

Aspect	Details
Gene	CLCN1 (Chloride Voltage-Gated Channel 1)
Chromosome	7q34-35
Method	Sanger sequencing of all 23 exons of CLCN1; increasingly replaced by next-generation sequencing (NGS) gene panels that simultaneously test CLCN1, SCN4A, CACNA1S, KCNJ2, and other skeletal muscle channelopathy genes
Mutations	> 300 known pathogenic variants — missense, nonsense, splice-site, small insertions/deletions, whole-exon deletions
Interpretation	Finding a known pathogenic or likely pathogenic variant in CLCN1 confirms the diagnosis. Heterozygous pathogenic variant + AD phenotype = Thomsen disease. Homozygous or compound heterozygous pathogenic variants + AR phenotype = Becker disease.
Variants of uncertain significance (VUS)	A CLCN1 VUS does NOT confirm the diagnosis — clinical-electrophysiological correlation is essential. Functional studies or segregation analysis in family members may be needed.
Negative result	If CLCN1 sequencing is negative but clinical suspicion remains high, consider: (1) large deletions/duplications not detected by sequencing (MLPA may help); (2) deep intronic variants; (3) reconsider the diagnosis — could it be SCN4A (PMC) or DM2 (CNBP)?
Availability in HK	Available through Clinical Genetics Service at QMH/HKCH, or can be sent to accredited overseas laboratories. Turnaround time: weeks to months.

Why Gene Panels Over Single-Gene Testing?

Modern practice increasingly uses multigene NGS panels for skeletal muscle channelopathies rather than sequential single-gene Sanger sequencing. A typical "non-dystrophic myotonia / periodic paralysis" panel includes CLCN1, SCN4A, CACNA1S, KCNJ2, KCNJ5, and RYR1. This approach is:

More efficient (tests all relevant genes simultaneously)
More cost-effective (one test instead of sequential tests)
More likely to catch unexpected diagnoses (e.g., a patient thought to have MC who actually has an SCN4A variant)

These are not diagnostic OF MC but are needed to rule out mimics:

Investigation	Purpose	Expected in MC
Slit-lamp examination	Exclude cataracts (DM1)	Normal — no cataracts
ECG	Exclude cardiac conduction defects (DM1)	Normal — no PR prolongation, no bundle branch block
Echocardiography	Exclude cardiomyopathy (DM1, DCM associated with neuromuscular disorders)	Normal
HbA1c / Fasting glucose	Exclude DM (DM1 association)	Normal
Gonadal hormones (in males)	Exclude testicular atrophy (DM1)	Normal
Cognitive assessment	Exclude cognitive decline (DM1)	Normal

Neuromuscular disorders [associated with familial DCM]: Duchenne muscular dystrophy, Becker muscular dystrophy, Myotonic dystrophy ^[8]

ECG / echo: dilated cardiomyopathy ^[5] — important to screen for in dystrophic myotonias, but expected to be NORMAL in MC.

If all of the above systemic screens are normal, this strongly supports a non-dystrophic myotonia and argues against DM1/DM2.

Aspect	Details
Role	Muscle biopsy is rarely needed in MC because the diagnosis is made clinically + EMG + genetics. Biopsy is reserved for atypical cases or when the diagnosis remains unclear after genetic testing.
Findings if performed	Non-specific: absence of dystrophic changes (no fibre necrosis, no regeneration, no fibrosis). May show type 2 fibre hypertrophy and absence of type 2B fibres (particularly in Becker MC). Occasional internal nuclei. These findings are non-diagnostic on their own.
Contrast with DM1	DM1 biopsy shows dystrophic changes: increased internal nuclei, ring fibres, sarcoplasmic masses, type 1 fibre atrophy, fibrosis.

Muscle biopsy [as investigation for muscle diseases] ^[3]^[5]^[7]

Step	Action	Rationale
1	History + Examination — confirm clinical myotonia (grip, percussion, eyelid); assess warm-up; assess for weakness and multisystem features	Clinical phenotyping
2	Exclude acquired causes — drug history, TFT, electrolytes	Rule out reversible causes
3	EMG + NCS — confirm myotonic discharges; normal NCS; assess MUAP morphology	Electrophysiological confirmation of true myotonia; exclude neuropathy; distinguish dystrophic (abnormal MUAPs) from non-dystrophic (normal MUAPs)
4	Screen for multisystem features — slit-lamp, ECG, echo, HbA1c, gonadal hormones, cognitive assessment	Exclude myotonic dystrophy
5	Genetic testing — CLCN1 (or NGS channelopathy panel)	Definitive confirmation; determine AD (Thomsen) vs AR (Becker); enable genetic counselling
6	Family screening — clinical ± genetic testing of at-risk relatives	Identify presymptomatic carriers; inform reproductive counselling

High Yield Summary — Diagnosis of Myotonia Congenita

No formal diagnostic criteria exist — diagnosis is a clinical-electrophysiological-genetic triad.
Bedside tests: grip myotonia, percussion myotonia, eyelid myotonia, warm-up phenomenon.
CK: Normal or mildly elevated (< 2–3× ULN) — muscle structure is intact, unlike dystrophies.
EMG: Myotonic discharges (waxing/waning, "dive-bomber" sound) with normal voluntary MUAPs. This pattern = non-dystrophic myotonia.
NCS: Normal — confirms the problem is in the muscle membrane, not the nerve.
Genetic testing: CLCN1 mutation analysis is the gold standard. AD = Thomsen, AR = Becker. NGS gene panels are now preferred.
Exclude DM1: Slit-lamp (cataracts), ECG (conduction defects), echo (cardiomyopathy), HbA1c, gonadal hormones, cognitive screen — all should be NORMAL in MC.
Muscle biopsy: Rarely needed; non-specific findings (no dystrophy, type 2 fibre hypertrophy).
TFT: Must be checked to exclude hypothyroid pseudomyotonia.

Active Recall - Diagnosis of Myotonia Congenita

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 145: Myotonic dystrophy, causes and diagnosis of myotonia) ^[2] Senior notes: Ryan Ho Neurology.pdf (pp. 191–194: Diseases of muscles, ion channelopathies, non-dystrophic myotonic syndromes) ^[3] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 134, 143: Approach to generalized weakness investigations, myopathy investigations) ^[4] Lecture slides: GC 056. Generalized muscle weakness.pdf (Muscular dystrophies classification) ^[5] Senior notes: Maksim Medicine Notes.pdf (p. 276: Myopathy investigations, CK interpretation, myotonic dystrophy features) ^[7] Senior notes: Ryan Ho Fundamentals.pdf (p. 336: Generalized weakness investigation approach) ^[8] Senior notes: Block A - Inherited Cardiac conditions.pdf (p. 5: Neuromuscular disorders associated with familial DCM)

Management of Myotonia Congenita

Before diving into specific therapies, it is important to establish the overarching principles. Myotonia congenita is a benign, non-progressive channelopathy with normal life expectancy. The muscle is structurally intact — the problem is purely electrical. This fundamentally shapes the management philosophy:

Principle	Rationale
1. There is no cure	The underlying genetic defect (CLCN1 mutation) cannot be corrected. Management is symptomatic.
2. Not all patients require pharmacotherapy	Many patients with mild MC (especially Thomsen type) adapt well to their stiffness using the warm-up phenomenon and lifestyle modifications. Drug treatment is reserved for those whose myotonia significantly impairs daily function.
3. The goal is to reduce myotonia	We aim to reduce the frequency and severity of muscle stiffness so the patient can function normally — open jars, start walking without falling, drive safely, perform work tasks.
4. Avoid triggers	Cold exposure, prolonged rest, sudden movements — all worsen myotonia. Non-pharmacological measures targeting these triggers are first-line.
5. Genetic counselling is integral	AD (Thomsen) or AR (Becker) inheritance has implications for family planning and screening of relatives.
6. Multidisciplinary approach	Physiotherapy, occupational therapy, genetic counselling, and in paediatric cases, school support.

Mx [of non-dystrophic myotonic syndromes]: procainamide, phenytoin, disopyramide, nifedipine, quinine sulphate ^[2]

No specific treatment [for myopathy in general]. Supportive care with multidisciplinary approach: PT, OT, genetic counselling ^[5]

3. Non-Pharmacological Management (First-Line for All Patients)

These measures exploit the known pathophysiology of MC and should be tried before any drug is introduced.

Topic	Content	Rationale
Nature of the disease	Explain that MC is a lifelong but benign condition with normal life expectancy. The muscles are healthy — they are just "too excitable."	Reduces anxiety. Many patients (or parents of affected children) fear progressive disability akin to muscular dystrophy. Reassurance is powerful.
Warm-up technique	Teach the patient to perform gentle, repetitive contractions before any demanding activity — e.g., open and close the fist 10 times before gripping a tool; walk slowly for 30 seconds before jogging	Exploits the warm-up phenomenon: repeated use causes gradual Na⁺ channel inactivation and K⁺ clearance → membrane stabilizes → myotonia diminishes. This is the patient's built-in therapy.
Cold avoidance	Dress warmly; use gloves in cold weather; avoid cold water immersion; warm up indoors before going outside in winter	Cold worsens ClC-1 dysfunction and enhances Na⁺ channel recovery from inactivation → more repetitive firing → worse myotonia
Sudden movement avoidance	Avoid explosive starts from rest (e.g., sprinting from standstill). Always "warm up" first.	After prolonged rest, muscles are maximally stiff (no warm-up effect in play). Sudden explosive movement against stiff muscles can cause falls/injury.

Intervention	Details	Rationale
Regular aerobic exercise	Swimming (in warm water), cycling, walking — at moderate intensity	Regular activity keeps the warm-up effect partially maintained; improves cardiovascular fitness; the inherent muscle hypertrophy in MC means patients can be quite athletic once past the initial stiffness
Stretching programme	Gentle stretching of commonly affected muscle groups (calves, quadriceps, forearms)	Reduces subjective stiffness; maintains flexibility; does NOT directly treat myotonia but improves functional range
Physiotherapy referral	Especially for children or patients with Becker MC who have transient weakness	Tailored exercise programmes; gait training; fall prevention strategies

Intervention	Rationale
Adaptive tools (e.g., ergonomic grips, button hooks, elastic shoelaces)	Reduces functional impact of grip myotonia on daily activities
Workplace modifications	Avoiding cold environments; allowing warm-up time before tasks requiring fine motor control
School support (in children)	Educating teachers about the condition; allowing extra time for handwriting; avoiding embarrassment from visible stiffness

Topic	Details
Thomsen (AD)	Each child of an affected parent has a 50% chance of inheriting the mutation. Penetrance is high but expressivity variable.
Becker (AR)	Both parents are carriers (usually asymptomatic). Each child has a 25% chance of being affected, 50% chance of being a carrier, 25% chance of being unaffected and not a carrier.
Family screening	Offer clinical evaluation ± genetic testing to at-risk relatives
Prenatal/preimplantation diagnosis	Technically possible but rarely pursued given the benign nature of MC

4. Pharmacological Management

Drugs are indicated when myotonia significantly impairs daily function despite non-pharmacological measures. All anti-myotonic drugs work by the same fundamental principle: they stabilize the sarcolemmal membrane by blocking Na⁺ channels, thereby reducing the repetitive firing that constitutes myotonia.

Core Pharmacological Principle

Why Na⁺ channel blockers for a Cl⁻ channel disease? Because the myotonia in MC is caused by repetitive Na⁺-dependent action potentials (the problem is that reduced Cl⁻ conductance fails to prevent these). By partially blocking Na⁺ channels, you raise the threshold for firing and reduce the number of repetitive action potentials → less myotonia. You are treating the downstream electrical consequence, not the upstream Cl⁻ defect.

Aspect	Details
Drug class	Class IB antiarrhythmic; oral Na⁺ channel blocker (use-dependent — blocks channels more when they are rapidly firing, which is exactly what happens in myotonia)
Name breakdown	Related to lidocaine ("mexi-" from its origin as a Mexican derivative of lidocaine; "-letine" = oral bioavailability modification)
Mechanism in MC	Binds preferentially to Na⁺ channels in the inactivated state → stabilizes inactivation → reduces repetitive firing → less myotonia. Use-dependent: the more the channel fires, the more drug binds → selectively targets hyperexcitable fibres without significantly affecting normal muscle function.
Evidence	The MYOMEX trial (2017) — a multicentre, randomized, placebo-controlled trial — demonstrated that mexiletine significantly reduces myotonia (measured by clinical grading and EMG) in patients with non-dystrophic myotonia including MC [current evidence base, 2017–present]. This is the highest-level evidence available.
Dose	Start low: 150 mg PO once or twice daily. Titrate up to a maximum of 200 mg TDS (600 mg/day) based on response and tolerability.
Onset	Clinical improvement typically within days to 1–2 weeks.
Side effects	GI (nausea, dyspepsia — most common, dose-limiting); dizziness; tremor; cardiac (QT prolongation, pro-arrhythmic potential).
Monitoring	ECG before starting (to check baseline QTc) and periodically during treatment. Avoid in patients with pre-existing cardiac conduction abnormalities (prolonged QT, heart block, structural heart disease).
Contraindications	Significant cardiac conduction disease; long QT syndrome; severe hepatic impairment (mexiletine is hepatically metabolized via CYP2D6 and CYP1A2).

High Yield: Mexiletine = First-Line for Non-Dystrophic Myotonia

Mexiletine is the only drug with Level 1 evidence (RCT) supporting its use in non-dystrophic myotonia. It is the current first-line pharmacotherapy recommended by international neuromuscular guidelines. Always perform a baseline ECG before initiation and monitor QTc.

These are used when mexiletine is contraindicated, not tolerated, or insufficiently effective. Evidence for these is limited (case series, expert opinion, historical use).

Mx [of non-dystrophic myotonic syndromes]: procainamide, phenytoin, disopyramide, nifedipine, quinine sulphate ^[2]

Drug	Class / Mechanism	Dose (typical)	Key Points
Lamotrigine	Anticonvulsant; Na⁺ channel blocker (voltage-dependent, blocks sustained repetitive firing)	25 mg/day → titrate slowly to 100–300 mg/day	Favourable side-effect profile compared to Class I antiarrhythmics; avoids cardiac risk; effective in some patients; requires slow titration to avoid Stevens-Johnson syndrome (SJS). Increasingly used as preferred second-line.
Carbamazepine	Anticonvulsant; Na⁺ channel blocker (stabilizes inactivated state)	200 mg BD → up to 600–800 mg/day	Effective for myotonia in some patients; side effects include drowsiness, ataxia, hyponatraemia (SIADH), bone marrow suppression; requires monitoring of FBC and Na⁺. HLA-B*15:02 screening recommended in Han Chinese before use (risk of SJS/TEN).
Phenytoin	Anticonvulsant; Na⁺ channel blocker	100 mg BD–TDS	Historical use; narrow therapeutic index; side effects include gingival hypertrophy, hirsutism, cerebellar toxicity, osteomalacia; zero-order kinetics make dosing unpredictable. Less preferred in modern practice.
Acetazolamide	Carbonic anhydrase inhibitor → mild metabolic acidosis → membrane stabilization; also modifies Cl⁻/HCO₃⁻ exchange	250 mg BD	Particularly useful in some Na⁺ channel myotonias ("acetazolamide-responsive myotonia"); may also help in MC; side effects: paraesthesia, renal stones, metabolic acidosis, hypokalaemia.
Quinine sulphate	Na⁺ channel blocker; also blocks K⁺ channels	200–300 mg BD	Historical use; concerns about cardiotoxicity (QT prolongation), cinchonism (tinnitus, nausea, visual disturbance), thrombocytopenia. Largely fallen out of favour due to safety profile.
Procainamide	Class IA antiarrhythmic; Na⁺ channel blocker	Variable	Historical use; risk of drug-induced lupus (anti-histone antibodies), agranulocytosis; rarely used now.
Disopyramide	Class IA antiarrhythmic; Na⁺ channel blocker + anticholinergic	Variable	Anticholinergic side effects (dry mouth, urinary retention, constipation); may worsen glaucoma; cardiotoxic; rarely used.
Nifedipine	Calcium channel blocker (dihydropyridine)	10–20 mg TDS	Mechanism in myotonia unclear — possibly indirect membrane stabilization via Ca²⁺ modulation; limited evidence; may cause hypotension, peripheral oedema, flushing.

Drug Selection Hierarchy in Practice

Current practical approach (2024–2026 guidelines):

First-line: Mexiletine (strongest evidence)
Second-line if cardiac contraindication or intolerance: Lamotrigine (no cardiac risk, reasonable evidence)
Second-line alternative: Carbamazepine (effective but more side effects; HLA-B*15:02 screening in Chinese)
Third-line / historical: Phenytoin, acetazolamide, quinine
Rarely used now: Procainamide, disopyramide (cardiac and systemic toxicity)

The lecture slide listing ^[2] reflects historical options — in modern practice, mexiletine and lamotrigine dominate.

This is a critical safety issue that every clinician managing a patient with MC must be aware of.

Issue	Details	Rationale
Avoid succinylcholine (suxamethonium)	Absolutely contraindicated in MC	Succinylcholine is a depolarizing neuromuscular blocker. In MC, the hyperexcitable membrane responds to depolarization with massive, sustained myotonic contraction → rigid jaw (masseter spasm), generalized rigidity → impossible intubation, risk of rhabdomyolysis, hyperkalaemia, and cardiac arrest. This can be life-threatening.
Non-depolarizing agents are safe	Use rocuronium, vecuronium, atracurium, cisatracurium	These block the NMJ without causing depolarization → no myotonic trigger. They work normally in MC. Sugammadex for reversal is also safe.
Volatile anaesthetics	Generally safe (unlike malignant hyperthermia, which involves RYR1 mutations, NOT CLCN1). However, some reports suggest volatile agents may trigger or worsen myotonia in individual cases → use with caution.	MC is a Cl⁻ channelopathy, NOT an RYR1/DHP receptor disorder. MC is NOT associated with malignant hyperthermia. However, prudence dictates caution.
Cold	Maintain normothermia during surgery; warm IV fluids; warm operating theatre	Cold worsens myotonia → intraoperative stiffness can interfere with surgical positioning and ventilation
MedAlert bracelet / Anaesthetic alert card	All MC patients should carry one	Ensures any anaesthetist is aware of the condition in emergency situations

Exam Trap: MC vs Malignant Hyperthermia

Students often confuse myotonia congenita with malignant hyperthermia (MH) because both involve "muscle stiffness" during anaesthesia. They are completely different:

Feature	Myotonia Congenita	Malignant Hyperthermia
Gene	CLCN1 (Cl⁻ channel)	RYR1 or CACNA1S (Ca²⁺ release channel)
Trigger	Succinylcholine (depolarization)	Volatile anaesthetics (halothane, isoflurane) + succinylcholine
Mechanism	Repetitive APs → myotonic stiffness	Uncontrolled Ca²⁺ release from SR → sustained contraction → hypermetabolism
Features	Stiffness/rigidity, NO hyperthermia	Rigidity + hyperthermia + metabolic acidosis + rhabdomyolysis + hyperK
Treatment	Avoid trigger; supportive	Dantrolene (blocks RYR1 Ca²⁺ release)

MC patients are NOT at increased risk of malignant hyperthermia. But succinylcholine must still be avoided ^[2].

Aspect	Frequency	Details
Clinical review	Every 6–12 months (stable patients); more frequently during drug titration	Assess myotonia severity (subjective + clinical tests), functional impact, medication side effects
ECG	Before starting mexiletine; 1–2 weeks after initiation or dose change; annually thereafter	Monitor QTc interval. Discontinue or reduce dose if QTc > 500 ms or increases by > 60 ms from baseline.
Blood tests	For carbamazepine: FBC + Na⁺ every 3–6 months. For phenytoin: drug levels.	Monitor for bone marrow suppression (carbamazepine), hyponatraemia (carbamazepine), supratherapeutic levels (phenytoin)
Functional assessment	Annually	Assess impact on ADLs, work, school; refer to OT/PT if needed
Genetic counselling update	At transition to adulthood; before family planning	Review inheritance, reproductive options

7. Special Populations

MC often presents in childhood. Pharmacotherapy is considered when stiffness significantly impairs motor milestones, play, school performance, or causes falls.
Mexiletine can be used in children (dose adjusted by weight); data are limited but clinical experience supports safety and efficacy.
Lamotrigine is an alternative with a well-established paediatric safety profile (used widely in childhood epilepsy).
Education of teachers and school staff is essential — the child may appear clumsy or slow to start movement but is NOT cognitively impaired.

Myotonia may worsen during pregnancy (hormonal and physiological changes).
Mexiletine: limited safety data in pregnancy (Category C). Use only if benefit outweighs risk; discuss with patient.
Lamotrigine: better pregnancy safety data (widely used in epilepsy in pregnancy, but levels drop in pregnancy due to increased clearance → may need dose adjustment).
Carbamazepine / Phenytoin: teratogenic (neural tube defects with carbamazepine; fetal hydantoin syndrome with phenytoin) — avoid if possible.
Labour and delivery: Myotonia is NOT a contraindication to vaginal delivery. However, anaesthetists must be informed (avoid succinylcholine if general anaesthesia needed). Regional anaesthesia (epidural/spinal) is safe and preferred.

Patients with the AR (Becker) form who have significant transient weakness at the onset of movement may benefit from pharmacotherapy even if the myotonia itself is tolerable, because the weakness can cause falls and injuries.
The warm-up technique is particularly important in this group — "always start slow."

Aspect	Details
Life expectancy	Normal — MC does not shorten life
Progression	Non-progressive — the degree of myotonia remains relatively stable over the lifespan (unlike DM1 which worsens)
Functional outcome	Most patients lead fully independent lives with appropriate management. Many are physically fit or even athletic (muscle hypertrophy is an advantage in some sports)
Complications	Rare — mainly related to falls (Becker MC with transient weakness) or anaesthetic incidents (if succinylcholine given inadvertently)

High Yield Summary — Management of Myotonia Congenita

No cure exists — management is symptomatic and supportive.
Non-pharmacological measures are first-line: warm-up technique, cold avoidance, physiotherapy, occupational therapy, patient education.
Mexiletine is the first-line drug (Class IB Na⁺ channel blocker, use-dependent). Start 150 mg OD/BD, max 200 mg TDS. Baseline ECG mandatory — monitor QTc.
Lamotrigine is the preferred second-line (no cardiac risk, familiar paediatric safety profile).
Historical options include procainamide, phenytoin, disopyramide, nifedipine, quinine sulphate ^[2] — mostly superseded by mexiletine and lamotrigine.
Succinylcholine is absolutely contraindicated — causes life-threatening myotonic crisis. Non-depolarizing agents are safe.
MC is NOT malignant hyperthermia — different gene (CLCN1 vs RYR1), different mechanism, different treatment.
Genetic counselling is essential (AD for Thomsen, AR for Becker).
Prognosis is excellent — normal life expectancy, non-progressive, most patients function independently.

Active Recall - Management of Myotonia Congenita

References

^[2] Senior notes: Ryan Ho Neurology.pdf (pp. 193–194: Non-dystrophic myotonic syndromes management — procainamide, phenytoin, disopyramide, nifedipine, quinine sulphate; malignant hyperthermia) ^[5] Senior notes: Maksim Medicine Notes.pdf (p. 276: Myopathy management — no specific treatment, supportive care, PT, OT, genetic counselling)

Complications of Myotonia Congenita

Before listing complications, it is essential to frame the discussion. Myotonia congenita is fundamentally a benign, non-progressive channelopathy. The muscle fibre is structurally intact — there is no degeneration, no fibrosis, no necrosis. The heart, brain, endocrine organs, and eyes are all unaffected (unlike myotonic dystrophy). Therefore, the complication profile of MC is remarkably limited compared to other neuromuscular disorders.

Most "complications" of MC are functional consequences of myotonia itself or iatrogenic (related to drug treatment or anaesthesia). There are no life-threatening systemic complications intrinsic to the disease.

Myotonia congenita: AD/AR inheritance, due to voltage-gated Cl⁻ channel mutation (7q35) ^[2] S/S: infancy/childhood onset, generalized myotonia which ↑ in cold and ↓ by warmth/exercise, minimal weakness ^[2]

1. Musculoskeletal Complications

Aspect	Details
Mechanism	Myotonia causes muscle stiffness at the initiation of movement. When a patient tries to stand up suddenly, start walking from rest, or respond to an unexpected event (e.g., stepping off a curb), the stiff muscles cannot respond quickly enough → the patient falls. In Becker MC, the transient weakness at the onset of movement compounds this risk — the legs are both stiff AND briefly weak.
Why it happens from first principles	At rest, the hyperexcitable membrane (due to reduced Cl⁻ conductance) has not undergone the warm-up process. The first contraction meets maximal membrane instability → intense myotonia → the patient's legs "lock up" → they topple forward. In Becker MC, the severe Cl⁻ loss causes massive initial depolarization that transiently inactivates Na⁺ channels → brief weakness precedes the warm-up.
Types of injury	Fractures (wrist, hip — from falls), dental injuries (facial falls), lacerations, head injuries. Children are particularly vulnerable (playground falls, sports).
Prevention	Teach the warm-up technique ("always start slow"); avoid sudden explosive movements; fall prevention strategies (OT assessment, home modifications if needed); consider pharmacotherapy if falls are recurrent.

Clinical Pearl: Falls in Becker MC

Falls are the single most common "complication" leading to medical attention in Becker MC. The combination of stiffness + transient weakness at movement onset is a recipe for stumbles. This is a legitimate reason to start mexiletine even if the patient otherwise tolerates the myotonia — preventing fractures is a valid indication.

Aspect	Details
Mechanism	Chronic involuntary repetitive muscle fibre activation acts as a form of isometric exercise → work hypertrophy of type 2 fibres. This produces the characteristic "Herculean" build.
Why this is usually NOT a complication	Most patients view their muscular build positively. Some MC patients are even competitive athletes. The hypertrophy reflects healthy, functioning muscle.
When it becomes a problem	Rarely, extreme hypertrophy of specific muscle groups (e.g., calves, masseter) can cause cosmetic concern or functional limitation. Masseter hypertrophy may contribute to temporomandibular joint (TMJ) strain. In children, prominent calf hypertrophy may initially be mistaken for Duchenne muscular dystrophy (pseudohypertrophy), causing diagnostic confusion and parental anxiety.

Aspect	Details
Mechanism	A small proportion of patients with Becker (AR) MC develop mild fixed proximal weakness later in life (typically after the 4th–5th decade). This is thought to result from decades of chronic hyperexcitability causing low-grade cumulative fibre damage, though the mechanism is incompletely understood.
Clinical significance	Generally mild (MRC grade 4/5 at worst); does NOT approach the severity of dystrophic myopathies; does not cause respiratory failure or loss of ambulation. CK may be mildly elevated during these episodes.
Contrast with DM1	In DM1, progressive weakness is the hallmark and leads to significant disability. In MC, any late weakness is minimal and should prompt reconsideration of the diagnosis if severe.

2. Anaesthetic Complications

This is arguably the most clinically important category of complications because it is preventable and potentially life-threatening.

Aspect	Details
Mechanism	Succinylcholine (suxamethonium) is a depolarizing neuromuscular blocking agent used for rapid-sequence intubation. It works by depolarizing the motor endplate. In a patient with MC, this depolarization spreads across a hyperexcitable sarcolemma → massive, sustained myotonic contraction of all skeletal muscles.
Clinical features	Masseter spasm (rigid jaw — cannot open mouth for intubation); generalized rigidity; inability to ventilate (chest wall rigidity); risk of rhabdomyolysis → myoglobinuria → acute kidney injury; hyperkalaemia (K⁺ released from damaged/contracted muscle) → cardiac arrhythmia → cardiac arrest.
Why this differs from malignant hyperthermia	In MH (RYR1 mutation), volatile anaesthetics trigger uncontrolled Ca²⁺ release from SR → sustained contraction + hypermetabolism + hyperthermia. In MC (CLCN1 mutation), the problem is purely sarcolemmal hyperexcitability → myotonic stiffness. There is NO hypermetabolic state, NO true hyperthermia (unless secondary to prolonged sustained contraction), and dantrolene is NOT effective (dantrolene blocks RYR1, which is normal in MC).
Prevention	Absolute avoidance of succinylcholine in all MC patients. Use non-depolarizing agents (rocuronium, vecuronium, cisatracurium). All MC patients should carry a MedAlert bracelet or anaesthetic alert card.
Management if it occurs	Stop succinylcholine immediately; supportive ventilation (may require emergency tracheostomy if jaw rigid); IV fluids for rhabdomyolysis prevention; monitor and treat hyperkalaemia (IV calcium gluconate, insulin-dextrose, nebulized salbutamol); monitor renal function; consider IV mexiletine or IV phenytoin to reduce myotonic stiffness (limited evidence).

Exam Must-Know: Succinylcholine is Absolutely Contraindicated

This is the single most testable complication of myotonia congenita. If asked "What is the most dangerous complication?", the answer is succinylcholine-induced myotonic crisis during general anaesthesia. It is preventable by using non-depolarizing agents. MC patients are NOT at risk of malignant hyperthermia (different gene, different channel).

Aspect	Details
Mechanism	The operating theatre is typically cold (18–22°C). IV fluids may be unwarmed. Cold worsens ClC-1 dysfunction (slows channel kinetics of already reduced Cl⁻ channels) and enhances Na⁺ channel recovery from inactivation → more repetitive firing → increased myotonia.
Clinical consequence	Increased muscle stiffness during surgery → difficulty with positioning, surgical access, and mechanical ventilation (chest wall rigidity).
Prevention	Maintain normothermia: warm IV fluids, forced-air warming blankets, warm operating theatre. Alert the anaesthetic and surgical team pre-operatively.

Aspect	Details
Mechanism	After general anaesthesia, the patient may experience exaggerated myotonia upon emergence — due to cold exposure, stress hormones (catecholamine surge on waking), and lack of warm-up during the period of immobility.
Clinical consequence	Difficulty moving, shivering (which can itself trigger myotonia), patient distress.
Prevention	Maintain warmth; allow gradual emergence; inform recovery room staff; reassure patient.

These are often under-recognized but significantly impact quality of life.

Complication	Mechanism / Details
Impaired motor function in daily life	Grip myotonia → difficulty opening jars, turning keys, shaking hands, using tools, typing. Leg myotonia → difficulty starting to walk, climbing stairs, getting up from chairs. Eyelid myotonia → difficulty opening eyes quickly (can impair driving safety). These are the primary source of disability in MC.
Impaired sports performance	Despite their muscular build, MC patients may underperform in sports requiring sudden bursts of activity (sprinting, ball-catching, combat sports). After the warm-up period they may perform well, but the initial stiffness is a handicap.
Psychosocial impact in children	Children with MC may be teased for appearing "clumsy" or "slow." They may avoid physical activities or be excluded from sports. This can affect self-esteem, peer relationships, and school participation. Teacher and peer education is essential.
Anxiety and frustration	Adults may feel frustrated by the unpredictability of stiffness (especially in cold weather or after rest). Anxiety about falling in public, difficulty with handshakes in professional settings, or concerns about passing the condition to children.
Occupational limitations	Certain occupations requiring rapid reflexive movements (e.g., firefighting, military combat, some forms of manual labour) may be challenging. Career counselling may be needed.
Driving safety	If eyelid or leg myotonia is severe and causes impaired ability to react quickly (e.g., sudden braking), driving safety may be a concern. In most jurisdictions, MC per se is not a bar to driving, but patients should be counselled.

These arise from the pharmacotherapy used to treat MC.

Drug	Complication	Mechanism	Prevention
Mexiletine	QT prolongation → Torsades de Pointes → sudden cardiac death	Mexiletine blocks cardiac Na⁺ channels (Class IB antiarrhythmic) → can prolong QT in susceptible individuals, especially in combination with other QT-prolonging drugs	Baseline ECG; monitor QTc; avoid in pre-existing long QT or structural heart disease; avoid co-prescription with other QT-prolonging agents (e.g., macrolides, antipsychotics, fluoroquinolones)
Mexiletine	GI intolerance (nausea, dyspepsia)	Direct GI irritant effect; dose-dependent	Take with food; start at low dose; dose titrate gradually
Carbamazepine	Hyponatraemia (SIADH)	Carbamazepine stimulates ADH release and potentiates ADH action on collecting ducts → water retention → dilutional hyponatraemia	Monitor serum Na⁺ every 3–6 months; educate patient about symptoms (confusion, nausea, seizures)
Carbamazepine	SJS/TEN (Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis)	HLA-B15:02 mediated hypersensitivity — particularly prevalent in Han Chinese* and Southeast Asian populations	*HLA-B15:02 screening mandatory before use in Chinese patients** — if positive, carbamazepine is contraindicated
Carbamazepine	Bone marrow suppression (agranulocytosis, aplastic anaemia)	Direct bone marrow toxicity (rare)	Monitor FBC periodically
Phenytoin	Gingival hypertrophy, hirsutism, cerebellar toxicity, osteomalacia	Fibroblast stimulation (gingiva), altered vitamin D metabolism (osteomalacia), cerebellar neurotoxicity at supratherapeutic levels; zero-order kinetics → small dose changes can cause large level changes	Monitor drug levels; dental hygiene counselling; vitamin D supplementation
Quinine sulphate	Cinchonism (tinnitus, nausea, visual disturbance), QT prolongation, thrombocytopenia	Direct ototoxicity and cardiac Na⁺/K⁺ channel blockade; immune-mediated platelet destruction	Largely fallen out of favour; avoid in modern practice

Understanding what does NOT happen in MC is as important as knowing what does — especially to distinguish MC from myotonic dystrophy.

Complication	Occurs in DM1?	Occurs in MC?	Why Not in MC?
Cataracts	Yes (posterior subcapsular)	No	Cataracts in DM1 are due to RNA toxicity affecting lens crystallins. In MC, the defect is limited to the skeletal muscle Cl⁻ channel → lens is unaffected.
Cardiac conduction defects (heart block, arrhythmias)	Yes (major cause of death)	No	ClC-1 is expressed almost exclusively in skeletal muscle, NOT in cardiac muscle. Cardiac muscle has different Cl⁻ channel subtypes. Therefore, the CLCN1 mutation does not affect cardiac electrophysiology.
Cardiomyopathy	Yes (dilated)	No	Same reason — cardiac muscle is not affected by CLCN1 mutations.
Respiratory failure	Yes (diaphragm/respiratory muscle weakness)	No	MC does not cause progressive muscle degeneration or respiratory muscle weakness.
Cognitive decline	Yes	No	CLCN1 is not expressed in the CNS. The RNA toxicity mechanism of DM1 (which affects neuronal function) is absent in MC.
Endocrinopathy (DM, testicular atrophy)	Yes	No	No multisystem RNA toxicity in MC.
Reduced life expectancy	Yes	No	Life expectancy in MC is normal.

Multisystem involvement [in DM1], incl.: ^[1]^[2]

Eyes: cataract

Cardiac: cardiomyopathy, conduction disorders

Endocrinopathy: DM, testicular atrophy

Smooth muscle disorder: e.g. gut motility disorder, constipation, poor bladder emptying

Cognitive dysfunction

High Yield: The Absence of Systemic Complications Is a Key Distinguishing Feature

If a patient with myotonia develops cataracts, cardiac conduction defects, or cognitive decline — reconsider the diagnosis. These features are inconsistent with MC and should prompt genetic testing for myotonic dystrophy (DM1 or DM2). The absence of systemic complications is what makes MC a benign condition with normal life expectancy.

Category	Complication	Severity	Preventable?
Musculoskeletal	Falls and traumatic injury	Moderate (fractures possible)	Yes — warm-up technique, pharmacotherapy
Musculoskeletal	Fixed late myopathy (Becker, rare)	Mild	No — inherent to disease
Anaesthetic	Succinylcholine-induced myotonic crisis	Life-threatening	Yes — absolute avoidance of succinylcholine
Anaesthetic	Cold-induced intraoperative stiffness	Moderate	Yes — maintain normothermia
Functional	Impaired ADLs, sports, occupation	Variable	Partially — warm-up, pharmacotherapy, OT
Psychosocial	Low self-esteem, anxiety, social isolation (especially children)	Variable	Yes — education, counselling, peer support
Iatrogenic	Mexiletine QT prolongation	Potentially serious	Yes — ECG monitoring, avoid QT-prolonging co-medications
Iatrogenic	Carbamazepine SJS/TEN	Severe	Yes — HLA-B*15:02 screening in Chinese

High Yield Summary — Complications of Myotonia Congenita

MC is a benign condition — complications are few and mostly functional or iatrogenic.
Falls are the most common complication (especially in Becker MC with transient weakness) → fractures, head injuries.
Succinylcholine-induced myotonic crisis is the most dangerous complication — life-threatening but completely preventable by using non-depolarizing agents. All patients need a MedAlert bracelet.
MC is NOT malignant hyperthermia — different gene, different channel, dantrolene does not help.
No systemic complications: no cataracts, no cardiac conduction defects, no cardiomyopathy, no respiratory failure, no cognitive decline, no endocrinopathy. If these appear → rethink the diagnosis (likely DM1).
Drug complications: mexiletine → QT prolongation; carbamazepine → hyponatraemia, SJS/TEN (HLA-B*15:02 screening in Chinese); phenytoin → gingival hypertrophy, cerebellar toxicity.
Life expectancy is normal.
Psychosocial impact (especially in children) is real and should not be neglected — education, counselling, and peer support are important.

Active Recall - Complications of Myotonia Congenita

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 145: Myotonic dystrophy multisystem features) ^[2] Senior notes: Ryan Ho Neurology.pdf (pp. 193–194: Non-dystrophic myotonic syndromes, ion channelopathies, malignant hyperthermia)

High Yield Summary

Myotonia Congenita — Key Points for Exams:

Definition: Non-dystrophic hereditary myotonia due to loss-of-function mutations in CLCN1 (voltage-gated Cl⁻ channel, chromosome 7q35).
Two forms: Thomsen (AD, milder, earlier onset) and Becker (AR, more severe, later onset, transient weakness).
Pathophysiology: Reduced Cl⁻ conductance → membrane hyperexcitability → repetitive action potentials → delayed relaxation (myotonia). Minor leakage → myotonia; major leakage → paralysis.
Cardinal symptom: Muscle stiffness (NOT weakness). Strength is preserved or even enhanced (muscle hypertrophy).
Warm-up phenomenon: Myotonia improves with repeated contraction — this distinguishes MC from paramyotonia congenita (where myotonia paradoxically worsens).
Cold worsening: Myotonia increases in cold temperatures.
No multisystem features: Unlike myotonic dystrophy, there are NO cataracts, cardiac conduction defects, endocrinopathy, or cognitive decline.
Signs: Grip myotonia, percussion myotonia, eyelid myotonia, muscle hypertrophy ("Herculean build"), normal reflexes, no wasting.
Prognosis: Generally benign; life expectancy is normal. The stiffness is the main source of disability.
Channelopathy framework: Cl⁻ channel → MC; Na⁺ channel → paramyotonia congenita / hyperK PP; Ca²⁺ channel → hypoK PP / malignant hyperthermia.

High Yield Summary — DDx of Myotonia Congenita

Always confirm true myotonia (EMG myotonic discharges) — exclude pseudomyotonia (hypothyroidism), contracture (McArdle), and neuromyotonia (Isaacs).
The #1 DDx is myotonic dystrophy (DM1 > DM2) — look for progressive weakness, wasting, cataracts, cardiac, endocrine, and cognitive features. If ANY of these are present, it is NOT MC.
Among non-dystrophic myotonias, the main DDx is paramyotonia congenita — distinguished by paradoxical myotonia (worsens with use) and Na⁺ channel gene (SCN4A).
HyperK periodic paralysis can have inter-ictal myotonia but is distinguished by episodic flaccid weakness with elevated K⁺.
Drug-induced myotonia (statins, chloroquine) is acquired and reversible — always take a drug history.
Warm-up phenomenon = MC; paradoxical worsening = PMC — this is the bedside differentiator.

High Yield Summary — Diagnosis of Myotonia Congenita

No formal diagnostic criteria exist — diagnosis is a clinical-electrophysiological-genetic triad.
Bedside tests: grip myotonia, percussion myotonia, eyelid myotonia, warm-up phenomenon.
CK: Normal or mildly elevated (< 2–3× ULN) — muscle structure is intact, unlike dystrophies.
EMG: Myotonic discharges (waxing/waning, "dive-bomber" sound) with normal voluntary MUAPs. This pattern = non-dystrophic myotonia.
NCS: Normal — confirms the problem is in the muscle membrane, not the nerve.
Genetic testing: CLCN1 mutation analysis is the gold standard. AD = Thomsen, AR = Becker. NGS gene panels are now preferred.
Exclude DM1: Slit-lamp (cataracts), ECG (conduction defects), echo (cardiomyopathy), HbA1c, gonadal hormones, cognitive screen — all should be NORMAL in MC.
Muscle biopsy: Rarely needed; non-specific findings (no dystrophy, type 2 fibre hypertrophy).
TFT: Must be checked to exclude hypothyroid pseudomyotonia.

High Yield Summary — Management of Myotonia Congenita

No cure exists — management is symptomatic and supportive.
Non-pharmacological measures are first-line: warm-up technique, cold avoidance, physiotherapy, occupational therapy, patient education.
Mexiletine is the first-line drug (Class IB Na⁺ channel blocker, use-dependent). Start 150 mg OD/BD, max 200 mg TDS. Baseline ECG mandatory — monitor QTc.
Lamotrigine is the preferred second-line (no cardiac risk, familiar paediatric safety profile).
Historical options include procainamide, phenytoin, disopyramide, nifedipine, quinine sulphate ^[2] — mostly superseded by mexiletine and lamotrigine.
Succinylcholine is absolutely contraindicated — causes life-threatening myotonic crisis. Non-depolarizing agents are safe.
MC is NOT malignant hyperthermia — different gene (CLCN1 vs RYR1), different mechanism, different treatment.
Genetic counselling is essential (AD for Thomsen, AR for Becker).
Prognosis is excellent — normal life expectancy, non-progressive, most patients function independently.

High Yield Summary — Complications of Myotonia Congenita

MC is a benign condition — complications are few and mostly functional or iatrogenic.
Falls are the most common complication (especially in Becker MC with transient weakness) → fractures, head injuries.
Succinylcholine-induced myotonic crisis is the most dangerous complication — life-threatening but completely preventable by using non-depolarizing agents. All patients need a MedAlert bracelet.
MC is NOT malignant hyperthermia — different gene, different channel, dantrolene does not help.
No systemic complications: no cataracts, no cardiac conduction defects, no cardiomyopathy, no respiratory failure, no cognitive decline, no endocrinopathy. If these appear → rethink the diagnosis (likely DM1).
Drug complications: mexiletine → QT prolongation; carbamazepine → hyponatraemia, SJS/TEN (HLA-B*15:02 screening in Chinese); phenytoin → gingival hypertrophy, cerebellar toxicity.
Life expectancy is normal.
Psychosocial impact (especially in children) is real and should not be neglected — education, counselling, and peer support are important.

Myotonia Congenita

1. Definition

2. Epidemiology

3. Anatomy and Function: The Skeletal Muscle Chloride Channel

3.1 Normal Skeletal Muscle Excitation

3.2 The ClC-1 Channel

4. Etiology and Pathophysiology

4.1 Genetic Basis

4.2 Pathophysiology — From Ion Channel to Symptom

Step 1: Loss of Cl⁻ Conductance

Step 2: Membrane Hyperexcitability

Step 3: Myotonia

Step 4: The "Warm-Up" Phenomenon

Step 5: Why Becker MC Has Transient Weakness

Step 6: Why Muscle Hypertrophy Occurs

4.3 Dominant vs Recessive Mechanism

5. Classification

6. Clinical Features

6.1 Symptoms

6.2 Signs

6.3 Key Distinguishing Features from Other Myotonic Conditions

7. Summary of Pathophysiology → Clinical Correlation

Active Recall - Myotonia Congenita

References

Tier 1: Differential Diagnosis of Myotonia (the Symptom)

A. Non-Dystrophic Myotonias (Channelopathies — No Muscle Degeneration)

B. Dystrophic Myotonias (Myotonia + Progressive Muscle Degeneration + Multisystem Disease)

C. Periodic Paralyses with Myotonia

D. Drug-Induced / Toxic Myotonia

E. Hypothyroid Myopathy

Tier 2: Broader Differential of Muscle Stiffness (Non-Myotonic Causes)

Differential Diagnosis Algorithm

Summary Table: Key Differential Diagnoses at a Glance

Approach to Differential Diagnosis in Practice

Active Recall - DDx of Myotonia Congenita

1. Diagnostic Criteria

2. Diagnostic Algorithm

3. Investigation Modalities — Detailed Interpretation

3.1 Bedside Clinical Tests

3.2 Blood Tests

3.3 Electrophysiology — NCS and EMG

A. Nerve Conduction Studies (NCS)

B. Needle Electromyography (EMG)

C. Exercise Testing / Cooling Protocols (Specialized)

3.4 Genetic Testing — The Gold Standard

3.5 Investigations to Exclude Differential Diagnoses

3.6 Muscle Biopsy — Usually NOT Required

4. Summary: Stepwise Diagnostic Approach

Active Recall - Diagnosis of Myotonia Congenita

1. Principles of Management

2. Management Algorithm

3. Non-Pharmacological Management (First-Line for All Patients)

3.1 Patient Education

3.2 Physiotherapy and Exercise

3.3 Occupational Therapy

3.4 Genetic Counselling

4. Pharmacological Management

4.1 First-Line: Mexiletine

4.2 Second-Line Agents

5. Anaesthetic Considerations

6. Monitoring and Follow-Up

7. Special Populations

7.1 Paediatric Patients

7.2 Pregnancy

7.3 Becker MC with Transient Weakness

8. Prognosis

Active Recall - Management of Myotonia Congenita

Overview: Why Complications Are Few

1. Musculoskeletal Complications

1.1 Falls and Traumatic Injury

1.2 Muscle Hypertrophy — Generally Advantageous But Occasionally Problematic

1.3 Fixed Myopathy (Late, Rare, Mainly Becker MC)

2. Anaesthetic Complications

2.1 Succinylcholine-Induced Myotonic Crisis

2.2 Cold-Induced Intraoperative Myotonic Stiffness

2.3 Residual Myotonia Post-Anaesthesia

3. Functional and Psychosocial Complications

4. Drug-Related Complications (Iatrogenic)

5. Complications That Do NOT Occur (Important Negatives)

Summary of Complications