Patau Syndrome (trisomy 13)
Patau syndrome is a severe chromosomal disorder caused by an extra copy of chromosome 13, presenting at birth with holoprosencephaly, cleft lip/palate, polydactyly, and major cardiac defects, with most affected infants dying within the first year of life.
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References
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13)
[2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13)
[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13)
[4] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13)
Patau Syndrome (Trisomy 13)
Patau syndrome is a chromosomal disorder caused by the presence of an extra copy of chromosome 13 (or presence of its material), resulting in severe multiple congenital anomalies [1][2]. It is classified as an aneuploidy — an abnormal copy number of one or more chromosomes, usually resulting from non-disjunction of paired chromosomes in meiosis or through anaphase lag [1].
Breaking down the terminology:
- "Trisomy" → Greek: tri = three, soma = body → three copies of a chromosome (instead of the normal two)
- "Patau" → named after Dr. Klaus Patau who first described the cytogenetic basis in 1960
- "Aneuploidy" → Greek: an = not, eu = good/normal, ploid = fold → abnormal number of chromosomes
Classical triad = Microphthalmia/Anophthalmia + Cleft lip or palate + Postaxial polydactyly [1][2]
High Yield Definition
Patau syndrome is a lethal chromosomal abnormality — the majority of prenatally diagnosed cases die in utero, and 90% die within the first year of life, with the majority dying within the first month [1]. It is one of the few autosomal trisomies (alongside trisomy 18 and trisomy 21) compatible with live birth; all other autosomal trisomies are uniformly lethal in utero.
Epidemiology
- 1 in 8,000–15,000 live births (varies by source; Adrian Lui notes cite 1/8,000, Felix Lai notes cite 1/15,000 — this discrepancy reflects different inclusion criteria and populations) [1][2]
- Slightly more common in males [1]
- Third most common autosomal trisomy after Down syndrome (trisomy 21) and Edwards syndrome (trisomy 18)
- Strong association with advanced maternal age (as with all trisomies due to non-disjunction)
- Risk increases exponentially after maternal age 35
- At age 35: ~1/7,000; at age 45: ~1/500 (approximate figures)
- Many cases (> 80%) result in spontaneous abortion in the first/second trimester — the live birth incidence is far lower than the conception incidence
- With universal antenatal screening (including first-trimester combined screening and Non-Invasive Prenatal Testing [NIPT]) available in Hong Kong, many cases are detected prenatally
- The live birth incidence in HK may be lower than global figures due to high uptake of prenatal screening and termination of affected pregnancies
- Hong Kong's Hospital Authority offers NIPT with high sensitivity (> 99%) for trisomy 13
| Risk Factor | Mechanism |
|---|---|
| Advanced maternal age | ↑ risk of meiotic non-disjunction due to ageing oocytes (the "production line" hypothesis: oocytes formed last in fetal life have fewer chiasmata and are ovulated last, increasing risk of non-disjunction) |
| Previous trisomy pregnancy | Slightly increased recurrence risk (~1%), suggests possible predisposition to non-disjunction |
| Robertsonian translocation carrier (parent) | If a parent carries a balanced Robertsonian translocation involving chromosome 13 (e.g., rob(13;14)), recurrence risk is significantly higher (theoretically up to 100% if carrier parent is homologous translocation, but practically ~1-2% if father is carrier, ~15% if mother is carrier for rob(13;14)) |
| Parental gonadal mosaicism | Rare; can cause recurrence in young parents |
Important Distinction
Students often confuse the recurrence risk. For free trisomy 13 (from non-disjunction): recurrence risk is low (~1% or less, slightly above population risk). For translocation trisomy 13: recurrence risk depends on the type of translocation and which parent is the carrier — always check parental karyotypes!
Anatomy and Function of Chromosome 13
- Chromosome 13 is an acrocentric chromosome (centromere near one end; short arm contains ribosomal RNA genes)
- It is a medium-sized chromosome containing approximately 300–400 genes
- Key genes on chromosome 13 relevant to the phenotype:
- RB1 (retinoblastoma gene) — tumour suppressor; overexpression in trisomy may paradoxically cause retinal dysplasia
- ZIC2 and SHH pathway genes — involved in midline development and holoprosencephaly
- FOXO1 — transcription factor involved in development
- Genes involved in cardiac morphogenesis, limb patterning, and CNS development
- The extra copy leads to gene dosage imbalance — 1.5× the normal amount of protein products from chromosome 13 genes
- This disrupts finely tuned developmental signalling pathways, particularly:
- Midline development (→ holoprosencephaly, cleft lip/palate)
- Cardiac morphogenesis (→ structural heart defects)
- Neural development (→ severe intellectual disability, CNS malformations)
- Ocular development (→ microphthalmia, coloboma)
- Limb patterning (→ polydactyly)
Aetiology
| Type | Frequency | Mechanism |
|---|---|---|
| Free trisomy 13 (full, non-mosaic) | ~75-80% | Non-disjunction during meiosis I (most common) or meiosis II in parental gamete (usually maternal); results in 47,XX/XY,+13 |
| Robertsonian translocation | ~20% | Translocation of the long arm of chromosome 13 onto another acrocentric chromosome (usually chromosome 14); karyotype may be 46,XX/XY,rob(13;14),+13 |
| Mosaicism | ~5% | Post-zygotic mitotic non-disjunction; some cells are 47,+13 and others are 46,N; may have milder phenotype |
| Partial trisomy 13 | Rare | Only a portion of chromosome 13 is triplicated; phenotype depends on the specific region duplicated |
Why does maternal age matter?
- Human oocytes begin meiosis I during fetal life and arrest at prophase I (dictyate stage)
- They remain arrested for decades until ovulation
- During this prolonged arrest, the cohesin proteins holding sister chromatids together gradually degrade
- Older oocytes → more cohesin degradation → ↑ risk that chromosomes will not segregate properly → non-disjunction
- This is the "cohesin fatigue" hypothesis, the most accepted mechanism for age-related aneuploidy
- Robertsonian translocation involves fusion of the long arms of two acrocentric chromosomes (13, 14, 15, 21, 22) at the centromere, with loss of the short arms
- The most common Robertsonian translocation involving chromosome 13 is rob(13;14) — the carrier has 45 chromosomes but is phenotypically normal (balanced)
- During meiosis, the translocation chromosome can segregate in several ways:
- Alternate segregation → normal or balanced carrier offspring
- Adjacent segregation → unbalanced → effective trisomy 13 or monosomy 13 (monosomy 13 is lethal)
Clinical Pearl
If a child is diagnosed with trisomy 13 due to Robertsonian translocation, both parents must have karyotyping to determine if one is a balanced carrier. This has major implications for genetic counselling and recurrence risk in future pregnancies.
Classification
- Full (free) trisomy 13 — 47,XX,+13 or 47,XY,+13
- Translocation trisomy 13 — most commonly rob(13;14)(q10;q10),+13
- Mosaic trisomy 13 — 47,+13/46,N (variable proportion)
- Partial trisomy 13 — duplication of part of chromosome 13 long arm
- Full trisomy → most severe, worst prognosis
- Translocation → similar to full trisomy (if effectively trisomic for all of 13q)
- Mosaic → variable phenotype depending on proportion and distribution of trisomic cells; may have longer survival and milder features
- Partial → depends on region duplicated; critical region for the full phenotype is 13q32→qter
Clinical Features
The clinical features of trisomy 13 reflect disruption of developmental pathways during embryogenesis. The midline is disproportionately affected (holoprosencephaly spectrum, cleft lip/palate, midline scalp defects) because chromosome 13 contains genes critical for midline signalling (particularly the SHH pathway and ZIC2).
| Symptom | Pathophysiological Basis |
|---|---|
| Poor feeding/failure to thrive | Central neurological impairment (holoprosencephaly) + structural oro-facial defects (cleft lip/palate) + cardiac failure from CHD → inadequate caloric intake and increased metabolic demand |
| Apnoeic episodes | Central apnoea from brainstem malformation + possible airway obstruction from midline defects |
| Seizures (neonatal period) | Cortical malformation (holoprosencephaly, pachygyria) → abnormal neuronal circuitry → epileptogenesis |
| Hypotonia in neonatal period | CNS malformation → impaired upper motor neurone input + possible cerebellar hypoplasia |
| Recurrent infections | Immune dysfunction (possibly related to splenic/thymic anomalies) + aspiration from poor feeding/swallowing |
Signs (Physical Examination Findings)
| Sign | Pathophysiological Basis |
|---|---|
| Microcephaly with sloping forehead [2] | Impaired brain growth (holoprosencephaly spectrum) → reduced intracranial volume → small skull vault with receding forehead |
| Scalp defects (aplasia cutis congenita) [2] | Defective ectodermal/mesodermal development over the vertex; highly characteristic of trisomy 13 (present in ~50-75%) |
| Microphthalmia and hypertelorism [2] | Abnormal optic vesicle development + midline signalling defects (SHH pathway disruption) → small/absent eyes with wide-set orbits |
| Other eye defects: epicanthic fold, absent eyebrows, iris coloboma, retinal dysplasia [2] | Coloboma = failure of closure of the embryonic fissure (choroid fissure) of the optic cup; retinal dysplasia from RB1 gene dosage imbalance |
| Dysplastic/malformed ears [2] | Abnormal development of 1st and 2nd branchial arches |
| Cleft lip ± palate [2] | Failure of fusion of maxillary and medial nasal processes (lip) or palatine shelves (palate); related to midline signalling disruption |
| Short neck with redundant skin [2] | Likely related to overall growth restriction and cervical vertebral anomalies |
| Sign | Pathophysiological Basis |
|---|---|
| Holoprosencephaly (present in ~40-70%) | Failure of prosencephalon (forebrain) to cleave into two hemispheres; most severe = alobar (single ventricle, no interhemispheric fissure); related to SHH/ZIC2 pathway disruption |
| Severe intellectual disability | Cortical malformation + holoprosencephaly → profoundly abnormal neuronal migration and connectivity |
| Hypotonia → later hypertonia | Initial hypotonia from immature/damaged UMN pathways; later develops hypertonia as spasticity emerges |
| Sign | Pathophysiological Basis |
|---|---|
| VSD (most common) | Failure of interventricular septum formation during cardiac septation (weeks 4-8 of gestation) |
| ASD | Failure of atrial septum formation |
| PDA | Failure of ductus arteriosus closure postnatally (though this is also a structural persistence) |
| Dextrocardia | Abnormal left-right axis determination |
| Valvular anomalies | Abnormal endocardial cushion development |
Cardiac malformations are a major cause of early death in trisomy 13.
| Sign | Pathophysiological Basis |
|---|---|
| Postaxial polydactyly [2] (extra digit on ulnar/fibular side) | Disruption of limb patterning genes (SHH pathway) → duplication of digit anlage on the postaxial (ulnar/fibular) border |
| Single palmar transverse crease (simian crease) [2] | Abnormal dermatoglyphic development in early gestation; non-specific marker of chromosomal abnormality |
| Overlapping fingers | Abnormal tendon/joint development |
| Rocker-bottom feet (less common than in trisomy 18) | Abnormal tarsal bone development → convex sole |
| Sign | Pathophysiological Basis |
|---|---|
| Polycystic kidneys | Abnormal renal tubular development → cystic dilatation |
| Hydronephrosis | Structural obstruction from ureteric/pelvic anomalies |
| Cryptorchidism (males) | Failure of testicular descent — requires normal hormonal and anatomical signalling |
| Bicornuate uterus (females) | Failure of Müllerian duct fusion |
| Sign | Pathophysiological Basis |
|---|---|
| Capillary haemangiomata (especially forehead) | Abnormal vascular development |
| Cutis aplasia (scalp defects) | See above under craniofacial |
- Omphalocele — failure of midgut return to abdominal cavity
- Diaphragmatic hernia — defective pleuroperitoneal membrane closure
- Single umbilical artery — vascular developmental anomaly (normally 2 arteries, 1 vein)
| Feature | Trisomy 13 (Patau) | Trisomy 18 (Edwards) |
|---|---|---|
| Incidence | 1/8,000–15,000 | 1/3,000 |
| Sex ratio | Slightly M > F | F > M (4:1) |
| Classical triad | Microphthalmia + Cleft lip/palate + Polydactyly | Clenched hands + Rocker-bottom feet + Prominent occiput |
| CNS | Holoprosencephaly | Cerebellar hypoplasia |
| Hands | Polydactyly, simian crease | Overlapping fingers (index over 3rd, 5th over 4th) |
| Cardiac | VSD most common (~80%) | VSD most common (~100%) |
| Scalp | Aplasia cutis | Normal |
| Eyes | Microphthalmia, coloboma | Normal |
| Prognosis | Median survival ~7-10 days; 90% die < 1 year | Median survival 14 days; 5% reach 1 year |
| Recurrence | Low unless translocation | Low unless translocation |
- Intrauterine growth restriction (IUGR) is common
- Profound intellectual disability is universal in non-mosaic cases
- Developmental milestones are severely delayed or absent
- In mosaic cases, there may be some developmental progress, but still significant disability
- Communication: Diagnosis may be made prenatally (via NIPT/amniocentesis/CVS) or postnatally (clinical features + karyotype)
- Breaking bad news: Use a structured approach (e.g., SPIKES framework); acknowledge the severity of the diagnosis; provide written information
- Palliative care discussion: Given the poor prognosis, early involvement of palliative care team is appropriate
- Consent/assent: In the neonatal period, all decisions are made by parents with informed consent; discuss goals of care (comfort care vs. interventional approaches)
- Genetic counselling: Essential for recurrence risk — arrange parental karyotyping if translocation identified
Paediatric Communication Pearl
When discussing Patau syndrome with parents, avoid phrases like "incompatible with life" — instead, explain that "most babies with this condition have a very short life, but we will focus on comfort and quality of time together." Family-centred care means supporting the family through grief while respecting their wishes regarding level of intervention.
High Yield Summary
Patau Syndrome (Trisomy 13) — Key Points:
- Definition: Aneuploidy with extra chromosome 13; 75-80% from meiotic non-disjunction, ~20% Robertsonian translocation, ~5% mosaic
- Epidemiology: 1/8,000–15,000 live births; associated with advanced maternal age; slightly more common in males
- Classical Triad: Microphthalmia + Cleft lip/palate + Postaxial polydactyly
- CNS: Holoprosencephaly (pathognomonic association), severe ID, seizures
- Cardiac: ~80% have CHD (VSD most common)
- Other key features: Scalp defects (aplasia cutis), single palmar crease, polycystic kidneys, cryptorchidism
- Prognosis: Lethal — 90% die within first year, median survival ~7-10 days
- Recurrence risk: Low for free trisomy (~1%); higher for translocation carriers → always karyotype parents
- Compared to Trisomy 18: Trisomy 13 has MORE midline defects (holoprosencephaly, cleft lip) and polydactyly; Trisomy 18 has clenched fists and prominent occiput
- Prenatal detection: NIPT, first-trimester combined screening, amniocentesis/CVS for confirmation
Active Recall - Patau Syndrome (Trisomy 13)
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13) [2] Senior notes: Adrian Lui Pediatrics Notes.pdf, p.505 — Edward and Patau Syndromes [3] Senior notes: Ryan Ho Opthalmology.pdf, p.122 — Congenital Cataract (mentions Patau in syndromal causes) [4] Lecture slides: Block C - The malformed child: hereditary syndromes and anomalies.pdf [5] Lecture slides: GC 151. The malformed child hereditary syndromes and anomalies.pdf [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p.581 — DiGeorge syndrome/chromosomal disorders context
Differential Diagnosis of Patau Syndrome (Trisomy 13)
When a neonate or fetus presents with the constellation of features suggestive of trisomy 13 — particularly the classical triad of microphthalmia + cleft lip/palate + postaxial polydactyly [1][2] — the differential diagnosis centres on conditions that share overlapping dysmorphic features. The key clinical task is to distinguish trisomy 13 from other syndromes that cause:
- Midline defects (holoprosencephaly, cleft lip/palate)
- Polydactyly
- Microphthalmia/anophthalmia
- Congenital heart disease + multiple congenital anomalies
- Severe intellectual disability with lethal prognosis
The definitive distinction requires cytogenetic confirmation (karyotype, chromosomal microarray, or FISH), but clinical pattern recognition guides the urgency and type of testing.
Systematic Differential Diagnosis
| Condition | Shared Features with T13 | Distinguishing Features | Why It Is Different |
|---|---|---|---|
| Edwards syndrome (Trisomy 18) [2][3] | Microcephaly, dysplastic ears, CHD (VSD), rocker-bottom feet, low BW, omphalocele, lethal prognosis | Prominent occiput (vs sloping forehead in T13); clenched fist with overlapping fingers (index over 3rd, 5th over 4th) — the "trisomy hand" [3]; cerebellar hypoplasia (not holoprosencephaly); NO polydactyly; NO microphthalmia; NO scalp defects; F > M = 4:1 [2] | Trisomy 18 affects posterior fossa preferentially (cerebellar hypoplasia), while T13 affects midline forebrain (holoprosencephaly). The hand posture is pathognomonic: T18 = clenched overlapping, T13 = polydactyly |
| Down syndrome (Trisomy 21) [3][7] | CHD (VSD), simian crease, hypotonia | Brachycephaly with flat occiput (opposite of T13's sloping forehead); upslanting palpebral fissures, epicanthic folds, Brushfield spots; much better prognosis (life expectancy 50-60y); AVSD most characteristic cardiac lesion; NO holoprosencephaly, NO polydactyly, NO microphthalmia [3] | Trisomy 21 causes relatively mild dysmorphism and is compatible with long-term survival. The facial gestalt is completely different |
Exam Tip — Distinguishing the Three Live-Birth Trisomies
The fastest way to distinguish T13, T18, and T21 on clinical examination:
- T13: Midline defects — cleft lip, microphthalmia, holoprosencephaly, polydactyly, scalp defects
- T18: Posterior features — prominent occiput, clenched overlapping fingers, rocker-bottom feet
- T21: Flat face — brachycephaly, upslanting palpebral fissures, hypotonia, relatively good prognosis
| Condition | Shared Features with T13 | Distinguishing Features | Why It Is Different |
|---|---|---|---|
| DiGeorge syndrome (22q11.2 deletion) [6][7] | Cleft palate, CHD (conotruncal defects), dysmorphic facies | CATCH-22 mnemonic: Cardiac (truncus arteriosus, interrupted aortic arch — conotruncal, NOT septal defects), Abnormal facies (bulbous nose, long face), Thymic hypoplasia/T-cell deficit, Cleft palate, Hypocalcaemia [6]; NO polydactyly; NO microphthalmia; NO holoprosencephaly; usually viable with variable ID | The cardiac defects in DiGeorge are characteristically conotruncal (outflow tract), reflecting 3rd/4th branchial pouch maldevelopment, while T13 causes septal defects (VSD/ASD). The hypocalcaemia from hypoparathyroidism is unique to DiGeorge |
| Wolf-Hirschhorn syndrome (4p deletion) | Microcephaly, CHD, cleft lip/palate, severe ID | "Greek warrior helmet" facies (prominent glabella, hypertelorism, broad nasal bridge); NO polydactyly; NO holoprosencephaly typically; seizures are very prominent | Different chromosomal basis; facial gestalt is distinctive |
| Condition | Shared Features with T13 | Distinguishing Features | Why It Is Different |
|---|---|---|---|
| Smith-Lemli-Opitz syndrome (SLOS) | Holoprosencephaly, polydactyly (postaxial), microcephaly, cleft palate, CHD, ambiguous genitalia | AR inheritance (7-dehydrocholesterol reductase deficiency → defective cholesterol synthesis); 2-3 toe syndactyly is characteristic; can confirm with elevated 7-dehydrocholesterol on biochemical testing; normal karyotype | SLOS is a cholesterol biosynthesis disorder. The SHH signalling pathway requires cholesterol for proper function, which is why SLOS and T13 share midline defects — both disrupt SHH signalling, but through different mechanisms (gene dosage in T13 vs. substrate deficiency in SLOS) |
| Meckel-Gruber syndrome | Postaxial polydactyly, microphthalmia, cleft lip/palate, CNS malformation (occipital encephalocele) | AR inheritance (ciliopathy); occipital encephalocele (not holoprosencephaly); enlarged cystic kidneys (Potter sequence); hepatic fibrosis/ductal plate malformation; normal karyotype | Meckel-Gruber is a ciliopathy — the cilia are critical for SHH signalling, so again there is overlap in midline defects. The triad of encephalocele + polycystic kidneys + polydactyly is pathognomonic |
| Pallister-Hall syndrome | Postaxial polydactyly, midline defects | Hypothalamic hamartoma (→ gelastic seizures, precocious puberty); bifid epiglottis; imperforate anus; AD inheritance (GLI3 mutation); NO microphthalmia; normal karyotype | GLI3 is downstream of SHH pathway — yet another example of midline defect overlap |
Unifying Concept — SHH Pathway
Many differentials of trisomy 13 share midline defects (holoprosencephaly, cleft lip, polydactyly) because they all disrupt the Sonic Hedgehog (SHH) signalling pathway through different mechanisms:
- Trisomy 13: Gene dosage imbalance affecting ZIC2/SHH regulators on chromosome 13
- SLOS: Cholesterol deficiency (SHH requires cholesterol modification for signalling)
- Meckel-Gruber: Ciliary defect (cilia transduce SHH signals)
- Pallister-Hall: GLI3 mutation (GLI3 is a downstream SHH transcription factor)
Understanding this pathway explains why these conditions look clinically similar despite having completely different genetic aetiologies.
| Condition | Shared Features with T13 | Distinguishing Features |
|---|---|---|
| Short-rib polydactyly syndromes (Types I-IV) | Postaxial polydactyly, midline defects | Severely shortened ribs (→ pulmonary hypoplasia → lethal); narrow thorax on radiograph; ciliopathies; AR; normal karyotype |
| Ellis-van Creveld syndrome | Postaxial polydactyly, CHD (especially single atrium/ASD), cleft lip | Short-limbed dwarfism; natal teeth; nail dysplasia; AR; viable with variable prognosis |
| Bardet-Biedl syndrome | Postaxial polydactyly, renal anomalies | Obesity, retinitis pigmentosa (not microphthalmia), hypogonadism, ID; presents later in childhood; ciliopathy; AR |
Holoprosencephaly (HPE) has a broad differential. When HPE is the presenting feature, consider:
| Condition | Key Features |
|---|---|
| Trisomy 13 | Most common chromosomal cause of HPE (~40-70% of T13 have HPE) |
| SHH mutations (isolated HPE) | Autosomal dominant; variable expressivity (can range from alobar HPE to single central incisor); normal karyotype |
| ZIC2 mutations | AR; HPE without facial dysmorphism typically |
| Maternal diabetes | Teratogenic effect; 1% risk of HPE in poorly controlled maternal diabetes |
| Fetal alcohol spectrum disorder | Midface hypoplasia; smooth philtrum; thin upper lip; NO polydactyly |
| SLOS | As above |
Omphalocele can be present in trisomy 13. When this is the presenting finding [5]:
| Condition | Key Distinction |
|---|---|
| Trisomy 13 | Omphalocele + classical triad; karyotype confirms |
| Trisomy 18 | Omphalocele + clenched fists, prominent occiput [2][5] |
| Beckwith-Wiedemann syndrome | Omphalocele + macroglossia + macrosomia + hyperinsulinaemic hypoglycaemia; associated with hepatoblastoma [5]; 11p15 imprinting defect |
| Isolated omphalocele | No syndromic features; better prognosis [5] |
Omphalocele is "likely syndromal" — always check for associated anomalies and consider karyotyping [5]
Congenital cataract can occur in Patau syndrome [4]. When leukocoria or congenital cataract is detected in a neonate, the syndromic differential includes:
- Down syndrome, Edwards syndrome, Patau syndrome, Turner syndrome [4]
- TORCH infections (rubella most classically)
- Persistent fetal vasculature
- Retinoblastoma (leukocoria — always exclude)
- Galactosaemia (oil-droplet cataract)
| Investigation | Purpose |
|---|---|
| Karyotype (gold standard) | Identifies trisomy, translocation type, mosaicism |
| Chromosomal microarray (CMA) | Detects microdeletions/duplications not visible on karyotype; useful if karyotype normal but phenotype suspicious |
| FISH for chromosome 13 | Rapid result (24-48h); useful for urgent confirmation; uses fluorescent probes specific to chromosome 13 |
| 7-dehydrocholesterol level | Elevated in SLOS → rules in cholesterol synthesis defect |
| Renal ultrasound | Polycystic kidneys (T13, Meckel-Gruber) vs. horseshoe kidney (T18) vs. normal |
| MRI brain | HPE spectrum (T13, SLOS) vs. posterior fossa abnormality (T18) vs. encephalocele (Meckel-Gruber) |
| Echocardiography | VSD/ASD/PDA (T13) vs. conotruncal defects (DiGeorge) vs. AVSD (T21) |
| Parental karyotype | Essential if translocation T13 identified — determines recurrence risk |
| Feature | Trisomy 13 | Trisomy 18 | Trisomy 21 | DiGeorge (22q11.2 del) | SLOS |
|---|---|---|---|---|---|
| Cleft lip/palate | +++ | ± | - | Cleft palate | + |
| Polydactyly | +++ (postaxial) | - | - | - | + (postaxial) |
| Microphthalmia | +++ | - | - | - | + |
| Holoprosencephaly | +++ | - | - | - | + |
| Scalp defect | +++ | - | - | - | - |
| Clenched fists | - | +++ | - | - | - |
| Prominent occiput | - | +++ | - | - | - |
| Hypotonia | + | - | +++ | - | + |
| Cardiac lesion | VSD, ASD, PDA | VSD (100%) | AVSD, VSD | Conotruncal | VSD, ASD |
| Karyotype | 47,+13 | 47,+18 | 47,+21 | del(22q11.2) | Normal |
| Prognosis | Lethal | Lethal | Good (50-60y) | Variable | Variable |
| Inheritance pattern | Sporadic (non-disjunction) or translocation | Sporadic | Sporadic or translocation | Usually sporadic microdeletion | AR |
High Yield Summary
Differential Diagnosis of Trisomy 13 — Key Exam Points:
- The three live-birth autosomal trisomies (13, 18, 21) are distinguished by their characteristic gestalt: T13 = midline, T18 = posterior, T21 = flat face
- Classical triad of T13 (microphthalmia + cleft lip/palate + postaxial polydactyly) narrows the differential significantly [1][2]
- When karyotype is normal but phenotype overlaps, think single-gene disorders disrupting SHH pathway: SLOS (cholesterol deficiency), Meckel-Gruber (ciliopathy), Pallister-Hall (GLI3)
- DiGeorge (22q11.2 deletion) shares cleft palate and CHD but has conotruncal cardiac defects and CATCH-22 features — no polydactyly or microphthalmia [6]
- Omphalocele is "likely syndromal" — always karyotype and look for associated anomalies (T13, T18, Beckwith-Wiedemann) [5]
- Scalp defects (aplasia cutis congenita) are relatively specific to T13 among the trisomies — a useful discriminating sign
- Definitive diagnosis requires cytogenetic confirmation (karyotype/CMA/FISH) — clinical diagnosis alone is insufficient
Active Recall - Differential Diagnosis of Trisomy 13
References
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13) [2] Senior notes: Adrian Lui Pediatrics Notes.pdf, p.505 — Edward and Patau Syndromes [3] Senior notes: Maksim Paediatric Notes.pdf, p.204 — Comparison table of trisomies [4] Senior notes: Ryan Ho Opthalmology.pdf, p.122 — Congenital Cataract syndromic causes [5] Senior notes: Maksim Surgery Notes.pdf, p.334 — Omphalocele and associated syndromes [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p.581 — DiGeorge syndrome (CATCH-22) [7] Senior notes: Ryan Ho Cardiology.pdf, p.185 — Syndromes associated with congenital heart disease
Diagnostic Criteria, Algorithm and Investigations for Patau Syndrome (Trisomy 13)
Unlike many medical conditions, trisomy 13 does not have "diagnostic criteria" in the traditional clinical sense (like the Jones criteria for rheumatic fever or the SAPPORO criteria for antiphospholipid syndrome). Instead, diagnosis follows a two-step approach:
- Clinical suspicion — based on the characteristic phenotype (prenatal ultrasonographic findings or postnatal dysmorphic features)
- Cytogenetic confirmation — karyotype, FISH, or chromosomal microarray (CMA) providing definitive proof of an extra chromosome 13
The clinical phenotype raises suspicion, but cytogenetic analysis is mandatory for definitive diagnosis — because (a) clinical features overlap with other conditions (as discussed in the differential diagnosis section), (b) the cytogenetic mechanism (free trisomy vs. translocation vs. mosaicism) has direct implications for recurrence risk and genetic counselling, and (c) phenotype severity varies.
Prenatal Diagnosis
Prenatal detection is the most common route to diagnosis in Hong Kong, given the high uptake of antenatal screening.
| Test | Timing | What It Measures | How It Works | Sensitivity for T13 |
|---|---|---|---|---|
| First-trimester combined screening | 11–13+6 weeks | Nuchal translucency (NT) on USS + maternal serum free β-hCG + PAPP-A | Increased NT reflects subcutaneous oedema (from cardiac failure or lymphatic dysfunction in aneuploid fetuses). In T13: ↓ free β-hCG and ↓ PAPP-A (contrast with T21 where β-hCG is ↑). Combined with maternal age, gives a risk score | ~90% detection rate (DR) for a 5% false-positive rate |
| Non-Invasive Prenatal Testing (NIPT) / cell-free fetal DNA (cffDNA) | ≥ 10 weeks | Cell-free fetal DNA fragments in maternal blood | During pregnancy, the placenta sheds DNA fragments into maternal circulation. NIPT uses next-generation sequencing to detect overrepresentation of chromosome 13 sequences. If there is proportionally more chr 13 DNA than expected → positive screen | > 99% sensitivity and > 99% specificity for T13; positive predictive value varies with prevalence (lower PPV than for T21 because T13 is rarer) |
| Second-trimester "quad screen" | 15–20 weeks | AFP, hCG, uE3, inhibin A | Less specific for T13; may show non-specific abnormalities | Lower sensitivity than first-trimester combined or NIPT |
NIPT — Key Exam Concept
NIPT is a screening test, not a diagnostic test. A positive NIPT result must be confirmed by invasive diagnostic testing (CVS or amniocentesis) before any irreversible decision (e.g., termination of pregnancy) is made. This is because:
- NIPT analyses placental DNA (not fetal DNA) — confined placental mosaicism can cause false positives
- The positive predictive value for T13 is lower (~40-50%) than for T21 (~90%) because T13 has a lower prevalence (PPV depends on prevalence by Bayes' theorem)
Structural anomalies on USS may be detected at the 18-22 week anomaly scan (or earlier):
| USS Finding | Pathophysiological Basis | Frequency in T13 |
|---|---|---|
| Holoprosencephaly | Failure of forebrain cleavage (SHH/ZIC2 disruption) | ~40-70% |
| Facial clefting | Failure of midline fusion | ~60-80% |
| Polydactyly | SHH pathway limb patterning disruption | ~60-70% |
| Cardiac defects (VSD, ASD) | Cardiac septation failure | ~80% |
| Increased nuchal translucency / cystic hygroma | Lymphatic/cardiac dysfunction | Common in 1st trimester |
| Echogenic kidneys / renal anomalies | Abnormal tubular development | ~30-40% |
| Omphalocele | Failure of midgut return | ~10-15% |
| Single umbilical artery | Vascular developmental anomaly | ~25% |
| IUGR / small for gestational age | Overall growth failure from chromosomal imbalance | Common |
| Polyhydramnios or oligohydramnios | Impaired swallowing (CNS) or renal dysfunction | Variable |
When multiple structural anomalies are detected on prenatal USS, karyotyping/CMA via amniocentesis or CVS should be offered — this is a standard-of-care recommendation in Hong Kong [8].
| Test | Timing | Specimen | Turnaround | Notes |
|---|---|---|---|---|
| Chorionic villus sampling (CVS) | 11–14 weeks | Placental trophoblast cells | Rapid FISH: 24-48h; Full karyotype: 10-14 days; CMA: 5-7 days | Earlier diagnosis → earlier counselling. Risk of confined placental mosaicism (false positive/negative). Procedure-related miscarriage risk ~0.1-0.2% |
| Amniocentesis | ≥ 15 weeks | Amniotic fluid (fetal cells — desquamated skin, urinary tract, GI epithelium) | FISH: 24-48h; Karyotype: 10-14 days; CMA: 5-7 days | Gold standard for prenatal cytogenetics. Procedure-related miscarriage risk ~0.1-0.2% |
| Cordocentesis | ≥ 18 weeks | Fetal blood from umbilical vein | Rapid karyotype: 48-72h | Rarely used now; higher complication rate; reserved for late or complex cases |
Postnatal Diagnosis
In cases not diagnosed prenatally, the diagnosis is suspected based on the characteristic clinical gestalt at birth:
Key clinical features that should trigger immediate suspicion:
- Classical triad: microphthalmia/anophthalmia + cleft lip/palate + postaxial polydactyly [1][2]
- Scalp defects (aplasia cutis congenita) — relatively specific for T13 among trisomies [2]
- Holoprosencephaly spectrum findings — midline facial defects, cyclopia (extreme) [3]
- Multiple congenital heart defects
- Single palmar transverse crease
Any neonate with ≥ 2 major congenital anomalies (especially involving midline structures) should have urgent cytogenetic analysis [8]
| Investigation | Specimen | What It Detects | Turnaround | When to Use |
|---|---|---|---|---|
| Conventional karyotype (G-banding) | Peripheral blood (lymphocytes) | Full chromosome complement; identifies free trisomy (47,+13), Robertsonian translocation, large structural rearrangements; detects mosaicism if sufficient cells analysed (typically 20-30 cells) | 7-14 days (requires cell culture) | Gold standard — should be performed in all cases. Identifies mechanism (free vs. translocation) which determines recurrence risk |
| FISH for chromosome 13 | Peripheral blood, buccal cells, or uncultured amniocytes | Rapid detection of copy number of chromosome 13 using locus-specific fluorescent probes (e.g., RB1 locus at 13q14) | 24-48 hours | Urgent confirmation when clinical suspicion is high and rapid result needed (e.g., for family counselling, palliative care decisions). Does NOT detect translocations — must follow up with full karyotype |
| Chromosomal microarray (CMA) | Blood or tissue | Detects copy number variants (CNVs) genome-wide at higher resolution than karyotype; identifies partial trisomy 13, small duplications/deletions | 5-7 days | Useful when: (1) karyotype is normal but phenotype is suspicious (partial trisomy); (2) need to define breakpoints of partial duplication; (3) additional CNVs suspected |
| Parental karyotype | Both parents' peripheral blood | Identifies balanced Robertsonian translocation carrier status | 7-14 days | Essential if infant's karyotype shows translocation trisomy 13 — determines recurrence risk for future pregnancies [1] |
Why Full Karyotype, Not Just FISH?
A common exam mistake: stating that FISH alone is sufficient for diagnosis. FISH only tells you the copy number of chromosome 13 — it cannot distinguish between free trisomy and translocation trisomy. Since translocation carriers have a significantly higher recurrence risk than free trisomy (non-disjunction), the full karyotype is mandatory to guide genetic counselling. FISH is for rapid preliminary confirmation only.
Once trisomy 13 is confirmed, a systematic evaluation of associated anomalies is needed to guide management (whether comfort care or active management):
| Investigation | Purpose | Expected Findings in T13 |
|---|---|---|
| Echocardiography | Assess structural cardiac defects | VSD (most common), ASD, PDA, dextrocardia, valvular anomalies; present in ~80% |
| Cranial ultrasound (neonates — through open fontanelle) | Assess brain structure | Holoprosencephaly (alobar/semilobar/lobar), ventriculomegaly, absent corpus callosum |
| MRI brain | More detailed CNS assessment if USS equivocal | HPE spectrum, cortical malformation, cerebellar anomalies |
| Renal ultrasound | Assess renal anomalies | Polycystic kidneys, hydronephrosis, horseshoe kidney |
| Ophthalmological assessment | Assess eye anomalies | Microphthalmia, anophthalmia, coloboma, retinal dysplasia, congenital cataract [4] |
| Hearing screening (OAE/ABR) | Congenital hearing loss | Sensorineural or mixed hearing loss from cochlear/auditory nerve anomalies |
| Abdominal USS | Assess GI/hepatic anomalies | Omphalocele, malrotation |
| Skeletal survey / X-rays | Assess skeletal anomalies | Polydactyly confirmation, vertebral anomalies, rib abnormalities |
| Blood glucose | Assess for neonatal hypoglycaemia | May occur due to poor feeding/endocrine dysfunction |
| Basic metabolic panel | Baseline electrolytes, renal function | May show renal impairment if significant renal anomalies |
| Karyotype Result | Interpretation | Recurrence Risk | Counselling Points |
|---|---|---|---|
| 47,XX,+13 or 47,XY,+13 | Free (non-disjunction) trisomy 13 — most common (~75-80%) | Low (~1%, slightly above population risk); increases with maternal age | Sporadic event; future pregnancies should be offered prenatal screening/NIPT |
| 46,XX,rob(13;14)(q10;q10),+13 | Translocation trisomy 13 — effectively trisomic for all of 13q via Robertsonian translocation | If parent is carrier: ~1-2% (paternal carrier) to ~15% (maternal carrier) for rob(13;14). If de novo: low | Parental karyotyping is mandatory [1]. If carrier parent identified → offer prenatal diagnosis in ALL future pregnancies |
| 47,+13/46,XX (or XY) | Mosaic trisomy 13 — proportion of trisomic cells varies | Similar to free trisomy (non-disjunction origin, usually post-zygotic) | Phenotype may be milder and longer survival possible; proportion of trisomic cells in different tissues correlates with severity |
| 46,XX,dup(13)(q32→qter) | Partial trisomy 13 — duplication of critical region | Depends on parental karyotype (may be inherited from balanced translocation carrier) | Phenotype depends on specific region duplicated; 13q32→qter is the critical region for full T13 phenotype |
Special Considerations in Paediatric Diagnosis
- Cranial USS can be performed through the open anterior fontanelle in neonates — non-invasive, no sedation required, done at bedside. This is preferred over MRI in the acute neonatal period
- Echocardiography — neonatal echo is essential; performed at bedside; should include assessment for ductal-dependent lesions (some cardiac defects in T13 may require prostaglandin E1 to maintain ductal patency while goals of care are discussed)
- Ophthalmological assessment — red reflex check at birth (part of routine newborn examination); formal ophthalmology review for microphthalmia, coloboma, congenital cataract [4]
- Communication: When trisomy 13 is diagnosed (prenatally or postnatally), use a structured approach to breaking bad news
- Prenatal counselling: Non-directive counselling — present information about prognosis, available options (continuation of pregnancy with palliative care plan, termination of pregnancy if within legal timeframe), and support services
- Postnatal: Involve palliative care team early; discuss goals of care; respect parental wishes regarding level of investigation and intervention
- Consent: All investigations in neonates require parental consent — explain purpose, risks, and implications of each test
Hong Kong Legal Framework
In Hong Kong, termination of pregnancy is permitted up to 24 weeks' gestation under the Offences Against the Person Ordinance (Cap. 212) if continuation poses greater risk to the mother's physical/mental health. For a lethal chromosomal abnormality like trisomy 13, this is generally considered to meet the criteria. Beyond 24 weeks, termination may be considered if there is substantial risk of serious handicap — legal and ethical consultation is advisable.
| Stage | Key Actions | Key Investigations |
|---|---|---|
| Prenatal screening | Risk estimation | 1st trimester combined screen, NIPT |
| Prenatal structural assessment | Detect anomalies | 18-22 week anomaly USS |
| Prenatal confirmation | Definitive cytogenetics | CVS or amniocentesis → FISH + karyotype ± CMA |
| Postnatal clinical recognition | Pattern recognition of triad | Clinical examination by experienced paediatrician/geneticist |
| Postnatal confirmation | Definitive cytogenetics | FISH (urgent) → full karyotype (mechanism) ± CMA |
| Post-diagnosis workup | Anomaly assessment | Echo, cranial USS, renal USS, ophthalmology, hearing |
| Genetic counselling | Recurrence risk assessment | Parental karyotyping (especially if translocation) |
High Yield Summary
Diagnosis of Trisomy 13 — Key Exam Points:
- No formal "diagnostic criteria" — diagnosis is clinical suspicion + cytogenetic confirmation
- NIPT has > 99% sensitivity but is a screening test — must confirm with CVS/amniocentesis before irreversible decisions
- FISH gives a rapid result (24-48h) but cannot distinguish free trisomy from translocation — always follow with full karyotype
- Full karyotype is the gold standard — identifies the cytogenetic mechanism (free vs. translocation vs. mosaic) which directly determines recurrence risk
- Parental karyotyping is essential if translocation identified — a balanced Robertsonian translocation carrier parent dramatically increases recurrence risk (up to ~15% if maternal carrier for rob(13;14))
- Post-diagnosis workup: Echocardiography, cranial USS, renal USS, ophthalmology, hearing screening — to define the full spectrum of anomalies and guide management decisions
- Critical region for the full T13 phenotype is 13q32→qter
- Prenatal USS clues: holoprosencephaly, facial clefting, polydactyly, cardiac defects, increased NT, single umbilical artery
Active Recall - Diagnosis of Trisomy 13
References
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13) [2] Senior notes: Adrian Lui Pediatrics Notes.pdf, p.505 — Edward and Patau Syndromes [3] Senior notes: Maksim Paediatric Notes.pdf, p.204 — Comparison table of trisomies [4] Senior notes: Ryan Ho Opthalmology.pdf, p.122 — Congenital Cataract syndromic causes [5] Senior notes: Maksim Surgery Notes.pdf, p.334 — Omphalocele and associated syndromes [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p.581 — DiGeorge syndrome [7] Senior notes: Ryan Ho Cardiology.pdf, p.185 — Syndromes associated with congenital heart disease [8] Lecture slides: GC 151. The malformed child hereditary syndromes and anomalies.pdf
Management of Patau Syndrome (Trisomy 13)
The management of trisomy 13 is fundamentally different from most paediatric conditions because it is a lethal chromosomal abnormality with no cure [1][3]. The approach centres on:
- Family-centred care — supporting the family through decision-making, grief, and bereavement
- Goals-of-care discussion — defining whether the approach is comfort-focused (palliative) or includes selective active interventions
- Symptom management — ensuring the infant is comfortable regardless of the chosen care pathway
- Multidisciplinary coordination — neonatology, genetics, cardiology, surgery, palliative care, social work, psychology
- Genetic counselling — recurrence risk, reproductive options for future pregnancies
General management: No cure. Supportive: PT, OT, ST. Regular screening for potential comorbidities. Specific treatment: drug, surgery, transplantation. Genetic counselling — Inheritance/sporadic → recurrence risk. Reproductive options: pre-implantation genetic diagnosis, prenatal diagnosis [3]
Paradigm Shift in Trisomy 13 Management
Historically, trisomy 13 was considered "incompatible with life" and only comfort care was offered. Current (2020s) practice recognises that some families wish for active interventions, and that selected infants (particularly those with mosaic trisomy 13 or less severe phenotypes) may benefit from cardiac surgery and other interventions. The decision should be individualised, shared between the medical team and the family, and based on the specific constellation of anomalies and the family's values. There is no single "right" approach.
Detailed Management by Domain
| Component | Details |
|---|---|
| Non-directive counselling | Present balanced information about the diagnosis, prognosis, and options. Avoid phrases like "incompatible with life" — instead explain median survival, range of outcomes, quality of life considerations |
| Options presented | (a) Continuation of pregnancy with palliative or active birth plan; (b) Termination of pregnancy (legal in HK up to 24 weeks, or beyond if substantial risk of serious handicap — case-by-case legal/ethical review) |
| Birth planning | If continuing: discuss place of delivery (tertiary centre with NICU access recommended), level of resuscitation desired, who should be present, memory-making wishes |
| Monitoring | Serial USS for growth, amniotic fluid volume, cardiac function; fetal wellbeing assessment |
| Parental karyotyping | If translocation T13 identified — essential for recurrence risk counselling before next pregnancy |
| Decision Point | Comfort Pathway | Active Pathway |
|---|---|---|
| Resuscitation | Warmth, drying, skin-to-skin with parents. No active resuscitation (no intubation, no chest compressions, no adrenaline) | Standard neonatal resuscitation per NRP/NLS guidelines if needed; intubation and ventilation if required |
| Monitoring | Minimal (no invasive monitoring) | Standard NICU monitoring: SpO₂, HR, RR, temperature |
| First assessment | Brief physical examination to confirm diagnosis; then focus on comfort | Full examination, blood gas, blood glucose, urgent FISH if not already confirmed prenatally |
| Family involvement | Maximise skin-to-skin contact; facilitate bonding; offer photographs, hand/footprints | Family present, kept informed; still maximise contact when infant is stable |
Resuscitation Decision — Key Ethical Principle
The decision on resuscitation should be made before delivery through shared decision-making. The medical team should explain the prognosis honestly while respecting parental autonomy. In Hong Kong, there is no legal obligation to provide futile treatment, but equally, parents who wish for active management should not be denied reasonable interventions without careful discussion. Document the agreed plan clearly in the medical notes.
This is appropriate for the majority of infants with full (non-mosaic) trisomy 13 when families choose comfort-focused care.
| Domain | Management | Rationale |
|---|---|---|
| Pain and distress | Oral sucrose for procedural pain; non-nutritive sucking; swaddling; low-dose oral morphine (0.05-0.1 mg/kg/dose q4h PRN) if significant distress or air hunger | Sucrose activates endogenous opioid pathways in neonates. Morphine for refractory distress — use lowest effective dose. Goal is comfort, not prolongation of life |
| Feeding | Encourage breastfeeding/breast milk if infant can coordinate suck-swallow-breathe; cup feeding or syringe feeding if cleft palate prevents latch; NG tube feeding if family desires nutritional support | Feeding is a basic comfort measure and facilitates bonding. Cleft lip/palate may require modified teat or palatal obturator |
| Thermoregulation | Skin-to-skin kangaroo care; warm environment | Neonates (especially low BW) are prone to hypothermia; skin-to-skin also promotes bonding and reduces infant stress |
| Respiratory support | Supplemental oxygen by nasal prongs if dyspnoeic; avoid invasive ventilation unless part of active pathway | Central apnoea from brainstem malformation is common; supplemental O₂ eases work of breathing without prolonging dying |
| Seizure management | Phenobarbitone (loading dose 20 mg/kg IV, maintenance 3-5 mg/kg/day) if seizures causing distress | Seizures from cortical malformation (HPE) may cause visible distress; treatment is for comfort, not for long-term seizure control |
| Environment | Private room; open visiting for family including siblings; chaplaincy/spiritual support; memory-making (photographs, hand/footprints, lock of hair) | Family-centred palliative care; create positive memories; support grief process |
| Bereavement support | Follow-up appointment at 6-8 weeks post-death with neonatologist/geneticist; referral to bereavement counsellor; connect with parent support groups | Grief is ongoing; medical follow-up addresses unanswered questions; genetic counselling for future pregnancies |
4. Active/Selective Intervention Pathway
For families who wish to pursue active management, or for infants with mosaic trisomy 13 or partial trisomy 13 where the phenotype may be less severe.
| Cardiac Lesion | Management Options | Considerations |
|---|---|---|
| PDA (if haemodynamically significant) | Medical closure: Ibuprofen (10 mg/kg then 5 mg/kg × 2 doses, 24h apart) or Paracetamol (15 mg/kg q6h for 3-7 days). Surgical PDA ligation if medical closure fails | Ibuprofen/paracetamol inhibit prostaglandin synthesis → promote ductal closure. Contraindicated if renal impairment (ibuprofen), active bleeding, NEC |
| VSD (large, causing heart failure) | Initial medical management of heart failure: Furosemide (1-2 mg/kg/dose PO/IV), Captopril (0.1-0.5 mg/kg/dose TDS PO), caloric supplementation. Surgical VSD repair if responsive to medical Mx and family wishes | Heart failure occurs when Qp:Qs > 2:1 (left-to-right shunt). Furosemide reduces preload (loop diuretic). Captopril reduces afterload (ACEi) → reduces L-to-R shunt. Surgery may be considered in selected cases |
| ASD | Usually well-tolerated haemodynamically; rarely requires intervention in infancy | ASD causes volume overload of right heart but is usually compensated in infancy |
| Ductal-dependent lesion (rare in T13) | Prostaglandin E1 (alprostadil) infusion 5-20 ng/kg/min IV to maintain ductal patency | Keeps ductus arteriosus open if systemic or pulmonary circulation depends on it; temporising measure while goals of care are discussed |
Cardiac surgery in trisomy 13: Several case series (Japan, North America) have reported improved survival with cardiac surgery (PA banding, VSD repair) in selected trisomy 13 infants, with 1-year survival rates of ~50-70% in surgically treated groups vs. ~5-10% without surgery. However, all survivors have profound intellectual disability. The decision must balance potential survival benefit against surgical risk and quality of life.
| Anomaly | Surgical Option | Timing | Notes |
|---|---|---|---|
| Omphalocele | Primary repair or staged closure (Silo → delayed closure) | Within days of birth if active pathway chosen | As per standard omphalocele management [5]; cover with warm saline-soaked gauze and cling film immediately at birth |
| Cleft lip | Cheiloplasty (lip repair) | ~3 months (rule of 10s: > 10 weeks, > 10 lbs, Hb > 10 g/dL) | Improves feeding and appearance; may be offered even on comfort pathway if family desires |
| Cleft palate | Palatoplasty | ~9-12 months | Improves feeding and reduces aspiration; relevant only if infant survives |
| Polydactyly | Surgical excision | Usually elective at 6-12 months | Low priority; may be deferred; performed if functional benefit |
| Inguinal hernia / cryptorchidism | Herniotomy / orchidopexy | As per standard paediatric timelines | Only if active pathway and infant is thriving |
| Problem | Management | Paediatric Dosing |
|---|---|---|
| Seizures | First-line: Phenobarbitone IV/PO; Second-line: Levetiracetam or Phenytoin | Phenobarbitone: load 20 mg/kg IV, maintenance 3-5 mg/kg/day. Levetiracetam: 10-30 mg/kg/day in 2 divided doses. Phenytoin: load 15-20 mg/kg IV (slowly, max 1 mg/kg/min) |
| Apnoea | Caffeine citrate (for apnoea of prematurity-type central apnoea) | Loading dose 20 mg/kg PO/IV, maintenance 5-10 mg/kg/day OD. Caffeine is a methylxanthine that stimulates the brainstem respiratory centre |
| Hydrocephalus (if progressive) | VP shunt or endoscopic third ventriculostomy | Only if causing symptomatic raised ICP and active pathway chosen |
| Intervention | Indication | Details |
|---|---|---|
| Modified teats/nipples | Cleft lip/palate preventing effective latch | Haberman feeder, NUK cleft palate teat; allow controlled milk flow without requiring suction |
| NG tube feeding | Inability to achieve adequate oral intake | Expressed breast milk or standard infant formula via NG; may transition to gastrostomy if long-term survival anticipated |
| Gastrostomy (PEG/Mic-Key) | Persistent feeding difficulties with failure to thrive, if active pathway | Surgical or endoscopic insertion; only if long-term nutritional support planned |
| Caloric fortification | Heart failure causing increased metabolic demand | Concentrated formula (e.g., increase from standard 67 kcal/100 mL to 80-100 kcal/100 mL) |
| Problem | Management |
|---|---|
| Microphthalmia | Conformer prosthesis to promote orbital growth; purely cosmetic/structural |
| Congenital cataract | Cataract extraction if significant effect on vision [4]; however, given severe ID, visual rehabilitation benefit is limited |
| Coloboma | No treatment; document and monitor |
A small proportion of trisomy 13 infants survive beyond infancy (up to ~5-10% at 1 year, with rare long-term survivors especially in mosaic/partial forms). For these children:
| Domain | Follow-Up |
|---|---|
| Developmental support | PT, OT, ST [3] — early intervention programme; all survivors have profound ID; focus on maximising quality of life and functional abilities |
| Comorbidity screening | Regular screening for potential comorbidities [3]: cardiac follow-up (echo), renal function monitoring, ophthalmology, audiology, growth monitoring |
| Growth | Plot on standard growth charts; T13-specific growth charts are available but not universally used; monitor for failure to thrive |
| Immunisations | Follow standard Hong Kong childhood immunisation schedule unless specific contraindications (e.g., severe immunodeficiency — rare in T13) |
| Education | Special educational needs assessment; early childhood intervention programme (Hong Kong: Child Assessment Service referral) |
| Topic | Key Points |
|---|---|
| Recurrence risk | Free trisomy: ~1% (empiric, slightly above population risk). Translocation: depends on carrier status (rob(13;14) maternal carrier ~15%, paternal ~1-2%) |
| Parental karyotyping | Mandatory if translocation identified [1] |
| Reproductive options [3] | Pre-implantation genetic testing (PGT) — IVF with embryo biopsy at blastocyst stage; select embryos without trisomy 13. Prenatal diagnosis — CVS or amniocentesis in future pregnancies. NIPT — as screening in future pregnancies. Donor gametes — if parental translocation with high recurrence risk |
| Psychosocial support | Grief counselling; connect with support groups (e.g., SOFT — Support Organisation for Trisomy 13/18/related disorders) |
Pre-Implantation Genetic Diagnosis — How It Works
Pre-implantation genetic diagnosis (PGD) [3] involves IVF to produce embryos, then biopsy of cells from the trophectoderm (outer layer of the blastocyst, day 5-6). These cells are analysed by CMA or FISH for chromosome 13 copy number. Only embryos with a normal complement are transferred to the uterus. This avoids the need for prenatal diagnosis and potential termination of pregnancy — particularly valuable for families who have moral/religious objections to TOP.
| Drug | Indication | Dose (Neonatal/Paediatric) | Route | Key Side Effects/Contraindications |
|---|---|---|---|---|
| Phenobarbitone | Neonatal seizures | Load: 20 mg/kg; Maint: 3-5 mg/kg/day | IV/PO | Respiratory depression, sedation; avoid in severe hepatic impairment |
| Levetiracetam | Seizures (2nd line) | 10-30 mg/kg/day in 2 divided doses | IV/PO | Irritability, somnolence; renal dose adjustment needed |
| Caffeine citrate | Central apnoea | Load: 20 mg/kg; Maint: 5-10 mg/kg/day | IV/PO | Tachycardia, feeding intolerance; monitor levels if concern |
| Ibuprofen | PDA closure | 10 mg/kg, then 5 mg/kg × 2 doses q24h | IV | Renal impairment, NEC, bleeding; CI in renal failure, active bleeding, NEC |
| Furosemide | Heart failure | 1-2 mg/kg/dose, 1-3 times daily | IV/PO | Hypokalaemia, hyponatraemia, ototoxicity; monitor electrolytes |
| Captopril | Heart failure (afterload reduction) | 0.1-0.5 mg/kg/dose TDS | PO | Hypotension, hyperkalaemia, renal impairment; CI in bilateral RAS |
| Morphine sulphate | Pain/distress (palliative) | 0.05-0.1 mg/kg/dose q4h PRN | PO/IV | Respiratory depression, constipation; titrate to comfort |
| Prostaglandin E1 (Alprostadil) | Ductal-dependent cardiac lesion | 5-20 ng/kg/min continuous infusion | IV | Apnoea (10-12%), hypotension, fever; must have airway support available |
| Issue | Approach |
|---|---|
| Withholding vs. withdrawing treatment | Both are ethically and legally equivalent in Hong Kong. Decisions should be based on best interests of the child with parental involvement |
| Medical futility | Interventions that prolong dying without improving quality of life may be considered futile — but this determination should be made collaboratively, not unilaterally by the medical team |
| Parental disagreement with team | If parents request interventions the team considers inappropriate (e.g., ICU admission, CPR), seek a second opinion, involve clinical ethics committee, and aim for consensus. Respect but do not defer blindly |
| Documentation | Goals-of-care discussion, resuscitation status, and agreed management plan must be clearly documented and regularly reviewed |
| Cytogenetic Type | Median Survival | 1-Year Survival | Long-Term |
|---|---|---|---|
| Full trisomy 13 | ~7-10 days | ~5-10% | Rare survivors beyond childhood; all have profound ID |
| Translocation T13 | Similar to full trisomy | Similar | Similar (effectively trisomic for entire 13q) |
| Mosaic T13 | Longer (months to years) | Higher (~30-50%) | Variable; some reach adulthood with severe-profound ID; phenotype depends on proportion and distribution of trisomic cells |
| Partial T13 | Variable | Variable | Depends on region duplicated; if critical region (13q32→qter) involved, similar to full; if not, may be milder |
Majority of prenatal diagnosed cases die in utero. 90% die within the first year with majority dying within the first month [1]
High Yield Summary
Management of Trisomy 13 — Key Exam Points:
- No cure — management is supportive and palliative for most cases [3]
- Two pathways: Comfort/palliative care vs. selective active intervention — determined by shared decision-making with the family
- Supportive care includes PT, OT, ST; regular screening for comorbidities [3]
- Cardiac surgery (VSD repair, PA banding, PDA ligation) may improve survival in selected cases but all survivors have profound ID — must discuss with family
- Palliative care: Symptom-focused — morphine for distress, phenobarbitone for seizures, feeding support, warmth, family bonding, bereavement care
- Cleft lip/palate repair may be offered for feeding improvement and quality of life even in the palliative pathway
- Genetic counselling is essential: Parental karyotyping if translocation; recurrence risk counselling; reproductive options include PGD and prenatal diagnosis [3]
- Key medications to know: Phenobarbitone (seizures), caffeine citrate (apnoea), PGE1 (ductal patency), furosemide + captopril (heart failure), morphine (comfort)
- Ethical framework: Shared decision-making, best interests of child, respect parental autonomy, clear documentation of goals of care
Active Recall - Management of Trisomy 13
References
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13) [2] Senior notes: Adrian Lui Pediatrics Notes.pdf, p.505 — Edward and Patau Syndromes [3] Senior notes: Maksim Paediatric Notes.pdf, p.202-204 — Genetics overview, general management principles [4] Senior notes: Ryan Ho Opthalmology.pdf, p.122 — Congenital Cataract management [5] Senior notes: Maksim Surgery Notes.pdf, p.334 — Omphalocele management [8] Lecture slides: GC 151. The malformed child hereditary syndromes and anomalies.pdf
Complications of Patau Syndrome (Trisomy 13)
Complications in trisomy 13 arise from two overlapping sources:
- Direct consequences of the congenital anomalies — the structural malformations present at birth (cardiac, CNS, renal, facial) lead to organ-specific complications
- Secondary complications — arising from the primary anomalies (e.g., aspiration pneumonia from cleft palate + poor swallowing; heart failure from VSD → pulmonary hypertension)
Because trisomy 13 is a multisystem disorder, complications span virtually every organ system. The key concept is that each congenital anomaly sets off a cascade of downstream problems — understanding this cascade from first principles is more valuable than memorising a list.
Cardiac anomalies are present in ~80% of trisomy 13 infants and are the leading cause of death [2].
| Complication | Mechanism (from first principles) | Clinical Significance |
|---|---|---|
| Congestive heart failure (CHF) | Large left-to-right shunts (VSD, ASD, PDA) → ↑pulmonary blood flow (Qp) relative to systemic blood flow (Qs) → pulmonary overcirculation → pulmonary oedema → ↑work of breathing + ↓systemic perfusion. In neonates, the fall in PVR over the first weeks of life unmasks the shunt, so CHF typically presents at 2-6 weeks of age | Presents with tachypnoea, feeding difficulty, failure to thrive, hepatomegaly, diaphoresis with feeds. Managed with furosemide + captopril (as discussed in management) |
| Pulmonary hypertension (pHTN) | Chronic left-to-right shunt → ↑pulmonary artery pressure → endothelial damage → vascular remodelling → ↑PVR. If PVR exceeds SVR → shunt reversal (Eisenmenger physiology) → cyanosis [7] | Develops over months-years if VSD is large and unrepaired. Eisenmenger syndrome = congenital L-to-R shunt + pulmonary arterial disease + cyanosis [7]. Once established, irreversible — cardiac repair is no longer feasible. In T13, most infants do not survive long enough to develop full Eisenmenger physiology, but it can occur in longer-surviving mosaic/partial cases |
| Arrhythmias | Structural abnormalities of the conduction system (abnormal cardiac septation → abnormal AV node/bundle of His development) + haemodynamic stress from shunt lesions | May cause sudden deterioration; difficult to manage in the context of underlying structural disease |
| Infective endocarditis (IE) | Turbulent flow across abnormal valves/septal defects → endothelial damage → nidus for bacterial seeding during bacteraemia | Rare in neonates (more relevant in longer survivors); standard IE prophylaxis should be considered for dental/surgical procedures in surviving children |
Eisenmenger Syndrome — Why Does the Shunt Reverse?
Initially, systemic pressure (LV) > pulmonary pressure (RV), so blood shunts left-to-right through the VSD. Chronic exposure of pulmonary arterioles to high pressure and high flow causes medial hypertrophy → intimal fibrosis → plexiform lesions (irreversible vascular remodelling). PVR rises progressively. When PVR ≥ SVR, the pressure gradient reverses → deoxygenated blood shunts right-to-left → systemic cyanosis. Signs include: loss of previous shunt murmur, loud P2, central cyanosis, clubbing [7]. This is the point of no return — surgical repair is contraindicated because the RV cannot tolerate the suddenly increased afterload if the "pop-off" shunt is closed.
| Complication | Mechanism | Clinical Features |
|---|---|---|
| Seizures | Holoprosencephaly and cortical malformation → abnormal neuronal architecture → epileptogenic circuits. The severity of HPE correlates with seizure burden — alobar HPE (most severe) typically has the most refractory seizures | Neonatal seizures may be subtle (apnoea, eye deviation, cycling movements) or overt (tonic-clonic). May be difficult to distinguish from normal neonatal movements — EEG confirmation helpful |
| Apnoeic episodes / central apnoea | Brainstem malformation (HPE spectrum extends to diencephalon and brainstem) → impaired central respiratory drive | Life-threatening; a common proximate cause of death. May respond to caffeine citrate if mild, but severe cases unresponsive to pharmacotherapy |
| Feeding difficulties / aspiration | Central coordination failure (suck-swallow-breathe reflex requires intact brainstem circuits — CN V, VII, IX, X, XII) + structural cleft lip/palate → discoordinated swallowing → aspiration | Leads to aspiration pneumonia (see respiratory complications below) |
| Profound intellectual disability | Global cortical and subcortical malformation → severely impaired neuronal connectivity and synaptic development | Universal in non-mosaic T13; no developmental milestones achieved in most cases; some mosaic cases may achieve limited milestones (social smile, head control) |
| Hydrocephalus | May develop secondary to holoprosencephaly (abnormal CSF circulation due to malformed ventricular system) or from associated Dandy-Walker malformation | Progressive head enlargement, bulging fontanelle, sunset sign, vomiting; requires VP shunt if active management pathway chosen |
| Complication | Mechanism | Management Considerations |
|---|---|---|
| Aspiration pneumonia | Impaired swallowing from CNS dysfunction + anatomical cleft lip/palate → recurrent aspiration of feeds/secretions → chemical pneumonitis → bacterial superinfection | Most common respiratory complication; may be recurrent and eventually fatal. Prevention: modified feeding techniques, thickened feeds, NG/gastrostomy feeding. Treatment: IV antibiotics (amoxicillin-clavulanate or co-amoxiclav covers oral flora and anaerobes) |
| Recurrent lower respiratory tract infections | Poor cough reflex (brainstem dysfunction) + possible immune dysfunction + pulmonary overcirculation from CHD → oedematous, poorly defended lungs | Frequent cause of hospitalisation in surviving infants |
| Pulmonary hypoplasia (if associated diaphragmatic hernia) | Diaphragmatic hernia → abdominal contents in thorax → compressed developing lung → hypoplastic lung with reduced alveolar and vascular development | Present at birth; causes severe respiratory failure; high mortality |
| Complication | Mechanism | Clinical Features |
|---|---|---|
| Renal failure | Structural renal anomalies (polycystic kidneys, dysplastic kidneys) → reduced functional nephron mass → progressive CKD | Monitor creatinine, electrolytes; may develop uraemia, fluid overload, electrolyte imbalance |
| Urinary tract infections (UTIs) | Structural anomalies (hydronephrosis, vesicoureteric reflux) → urinary stasis → bacterial colonisation | Common in infants with renal anomalies; present with fever, irritability, poor feeding; diagnosed by urine culture (suprapubic aspirate or catheter specimen in neonates) |
| Hypertension | Renal parenchymal disease → activation of RAAS (renin-angiotensin-aldosterone system) → sodium and water retention + vasoconstriction | Monitor BP; may require antihypertensives if active management pathway |
| Complication | Mechanism | Notes |
|---|---|---|
| Feeding difficulties | Multifactorial: cleft lip/palate (structural barrier to latch/suction), poor oromotor coordination (CNS), gastro-oesophageal reflux, heart failure (tachypnoea during feeds) | The most practical day-to-day challenge for families and clinicians; requires MDT input (speech therapy, dietetics, surgical team) |
| Failure to thrive / growth failure | Inadequate caloric intake (feeding difficulties) + increased metabolic demand (CHF, recurrent infections) + intrinsic growth restriction (chromosomal imbalance) | Weight gain is poor even with optimal feeding support; plot on growth charts and set realistic expectations with family |
| Gastro-oesophageal reflux (GOR) | Immature lower oesophageal sphincter (normal in neonates but exacerbated by hypotonia) + ↑intra-abdominal pressure from omphalocele repair | May worsen aspiration; managed with positioning (head-up 30°), feed thickening, anti-reflux medications (ranitidine/omeprazole) if needed |
| Omphalocele complications [5] | If omphalocele present and repaired: abdominal compartment syndrome (↑ intra-abdominal pressure after visceral reduction → difficult ventilation, ↓venous return → hypotension, ↓urine output, LL oedema, wound dehiscence) [5] | Post-op: monitor for abdominal compartment syndrome — difficult ventilation, reduced VR (hypotension, reduced urine output, LL oedema), wound dehiscence [5] |
| Complication | Mechanism | Notes |
|---|---|---|
| Microphthalmia / Anophthalmia [2] | Failure of optic vesicle development from abnormal gene dosage → small/absent globe | Requires orbital conformer prosthesis to promote orbital bone growth; purely structural/cosmetic |
| Coloboma (iris, retinal) [2] | Failure of closure of the embryonic fissure of the optic cup → gap in iris/retina/choroid | May cause visual field defects; increased retinal detachment risk |
| Retinal dysplasia [2] | Abnormal differentiation of retinal neuroepithelium (RB1 gene dosage effect) | Causes severe visual impairment |
| Congenital cataract [4] | Lens opacification from abnormal lens fibre development | Leukocoria; amblyopia; cataract extraction if significant effect on vision [4]; however, given severe ID, visual rehabilitation benefit is limited |
| Blindness | Cumulative effect of microphthalmia + retinal dysplasia + coloboma + cataract | Most T13 infants have severely impaired vision or are functionally blind |
| Complication | Mechanism | Notes |
|---|---|---|
| Recurrent infections | Multifactorial: (1) aspiration from swallowing dysfunction; (2) possible immune system immaturity/dysfunction; (3) structural anomalies creating foci (urinary tract, respiratory); (4) hospitalisation → nosocomial exposure | Most common cause of death after cardiac complications |
| Sepsis | Poor immune defences + frequent invasive procedures (NG tubes, IV lines, surgeries) + skin defects (scalp aplasia cutis → portal of entry) | Neonatal sepsis protocols apply; empiric antibiotics per local NICU guidelines |
| Complication | Mechanism |
|---|---|
| Hypotonia → contractures | Initial hypotonia from CNS malformation → with time, may develop hypertonia and fixed joint contractures due to lack of active movement and abnormal muscle tone |
| Scoliosis | Vertebral anomalies + hypotonia → progressive spinal deformity; relevant only in longer survivors |
| Complication | Mechanism |
|---|---|
| Polycythaemia (in longer survivors with cyanotic CHD) | Chronic hypoxaemia → EPO-driven erythrocytosis → ↑blood viscosity → risk of thrombosis (stroke, renal vein thrombosis) [7] |
| Anaemia (in neonatal period) | Frequent blood sampling in NICU + poor marrow compensation in critically ill neonate |
These are often under-recognised but are among the most impactful complications of trisomy 13.
| Complication | Mechanism / Explanation |
|---|---|
| Parental grief and psychological distress | Diagnosis of a lethal condition in one's child → anticipatory grief, depression, anxiety, PTSD (in up to 30% of parents); may begin at prenatal diagnosis or at birth |
| Marital/relationship strain | Disagreement about goals of care, financial burden, unequal caregiving burden → relationship stress |
| Sibling impact | Older siblings may not understand the situation; may feel neglected as parental attention is focused on the unwell infant; may experience guilt, confusion, or behavioural regression |
| Financial burden | NICU stay, specialist appointments, equipment, loss of parental income from caregiving → financial hardship |
| Moral distress in healthcare team | Clinicians may experience moral distress when parents request interventions the team perceives as prolonging suffering, or conversely when comfort care is chosen for an infant the team feels could benefit from intervention |
Family-Centred Care Reminder
Complications of trisomy 13 are not limited to the infant — the whole family is the patient. Always ask about parental coping, sibling wellbeing, and practical support needs. Refer to social work, psychology, and support organisations (e.g., SOFT — Support Organisation for Trisomy 13/18) early. Bereavement follow-up at 6-8 weeks post-death is standard of care.
| Cause | Approximate Contribution | Mechanism |
|---|---|---|
| Cardiopulmonary failure | ~50-60% | CHF from unrepaired CHD + pulmonary complications |
| Central apnoea | ~20-30% | Brainstem malformation → cessation of respiratory drive |
| Sepsis / pneumonia | ~10-20% | Aspiration + poor immune defences + nosocomial infections |
| Renal failure | < 5% | Bilateral renal dysplasia/polycystic disease |
Majority of prenatal diagnosed cases die in utero. 90% die within the first year with majority dying within the first month [1]
High Yield Summary
Complications of Trisomy 13 — Key Exam Points:
- Cardiac complications are the leading cause of death — CHF from large L-to-R shunts (VSD most common), progressing to pulmonary hypertension and potentially Eisenmenger syndrome in rare long survivors [2][7]
- Neurological: Seizures (from HPE/cortical malformation), central apnoea (brainstem malformation — common proximate cause of death), profound ID (universal)
- Respiratory: Aspiration pneumonia (from swallowing dysfunction + cleft palate) is the most common respiratory complication and a major cause of morbidity/mortality
- Renal: Progressive renal failure from structural anomalies; UTIs from urinary tract malformations
- Ophthalmological: Functional blindness from cumulative effect of microphthalmia, retinal dysplasia, coloboma, congenital cataract [2][4]
- Feeding / growth: Failure to thrive is universal due to multifactorial feeding difficulty + ↑metabolic demand
- Omphalocele post-op: Monitor for abdominal compartment syndrome [5]
- Psychosocial: Parental grief, sibling impact, financial burden — the whole family is the patient
- Most infants die from cardiopulmonary failure or central apnoea within the first month of life
Active Recall - Complications of Trisomy 13
References
[1] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p.835 — Patau Syndrome (Trisomy 13) [2] Senior notes: Adrian Lui Pediatrics Notes.pdf, p.505 — Edward and Patau Syndromes [4] Senior notes: Ryan Ho Opthalmology.pdf, p.122 — Congenital Cataract [5] Senior notes: Maksim Surgery Notes.pdf, p.334 — Omphalocele management and complications [7] Senior notes: Ryan Ho Cardiology.pdf, p.186 — Eisenmenger Syndrome [8] Lecture slides: CFB (OGPAE01-1) Perinatal Medicine, Antenatal Care and Pre-pregnant Counselling (Part I).pdf — USS screening for fetal anomalies, NIPT
High Yield Summary
Patau Syndrome (Trisomy 13) — Key Points:
- Definition: Aneuploidy with extra chromosome 13; 75-80% from meiotic non-disjunction, ~20% Robertsonian translocation, ~5% mosaic
- Epidemiology: 1/8,000–15,000 live births; associated with advanced maternal age; slightly more common in males
- Classical Triad: Microphthalmia + Cleft lip/palate + Postaxial polydactyly
- CNS: Holoprosencephaly (pathognomonic association), severe ID, seizures
- Cardiac: ~80% have CHD (VSD most common)
- Other key features: Scalp defects (aplasia cutis), single palmar crease, polycystic kidneys, cryptorchidism
- Prognosis: Lethal — 90% die within first year, median survival ~7-10 days
- Recurrence risk: Low for free trisomy (~1%); higher for translocation carriers → always karyotype parents
- Compared to Trisomy 18: Trisomy 13 has MORE midline defects (holoprosencephaly, cleft lip) and polydactyly; Trisomy 18 has clenched fists and prominent occiput
- Prenatal detection: NIPT, first-trimester combined screening, amniocentesis/CVS for confirmation
High Yield Summary
Differential Diagnosis of Trisomy 13 — Key Exam Points:
- The three live-birth autosomal trisomies (13, 18, 21) are distinguished by their characteristic gestalt: T13 = midline, T18 = posterior, T21 = flat face
- Classical triad of T13 (microphthalmia + cleft lip/palate + postaxial polydactyly) narrows the differential significantly [1][2]
- When karyotype is normal but phenotype overlaps, think single-gene disorders disrupting SHH pathway: SLOS (cholesterol deficiency), Meckel-Gruber (ciliopathy), Pallister-Hall (GLI3)
- DiGeorge (22q11.2 deletion) shares cleft palate and CHD but has conotruncal cardiac defects and CATCH-22 features — no polydactyly or microphthalmia [6]
- Omphalocele is "likely syndromal" — always karyotype and look for associated anomalies (T13, T18, Beckwith-Wiedemann) [5]
- Scalp defects (aplasia cutis congenita) are relatively specific to T13 among the trisomies — a useful discriminating sign
- Definitive diagnosis requires cytogenetic confirmation (karyotype/CMA/FISH) — clinical diagnosis alone is insufficient
High Yield Summary
Diagnosis of Trisomy 13 — Key Exam Points:
- No formal "diagnostic criteria" — diagnosis is clinical suspicion + cytogenetic confirmation
- NIPT has > 99% sensitivity but is a screening test — must confirm with CVS/amniocentesis before irreversible decisions
- FISH gives a rapid result (24-48h) but cannot distinguish free trisomy from translocation — always follow with full karyotype
- Full karyotype is the gold standard — identifies the cytogenetic mechanism (free vs. translocation vs. mosaic) which directly determines recurrence risk
- Parental karyotyping is essential if translocation identified — a balanced Robertsonian translocation carrier parent dramatically increases recurrence risk (up to ~15% if maternal carrier for rob(13;14))
- Post-diagnosis workup: Echocardiography, cranial USS, renal USS, ophthalmology, hearing screening — to define the full spectrum of anomalies and guide management decisions
- Critical region for the full T13 phenotype is 13q32→qter
- Prenatal USS clues: holoprosencephaly, facial clefting, polydactyly, cardiac defects, increased NT, single umbilical artery
High Yield Summary
Management of Trisomy 13 — Key Exam Points:
- No cure — management is supportive and palliative for most cases [3]
- Two pathways: Comfort/palliative care vs. selective active intervention — determined by shared decision-making with the family
- Supportive care includes PT, OT, ST; regular screening for comorbidities [3]
- Cardiac surgery (VSD repair, PA banding, PDA ligation) may improve survival in selected cases but all survivors have profound ID — must discuss with family
- Palliative care: Symptom-focused — morphine for distress, phenobarbitone for seizures, feeding support, warmth, family bonding, bereavement care
- Cleft lip/palate repair may be offered for feeding improvement and quality of life even in the palliative pathway
- Genetic counselling is essential: Parental karyotyping if translocation; recurrence risk counselling; reproductive options include PGD and prenatal diagnosis [3]
- Key medications to know: Phenobarbitone (seizures), caffeine citrate (apnoea), PGE1 (ductal patency), furosemide + captopril (heart failure), morphine (comfort)
- Ethical framework: Shared decision-making, best interests of child, respect parental autonomy, clear documentation of goals of care
High Yield Summary
Complications of Trisomy 13 — Key Exam Points:
- Cardiac complications are the leading cause of death — CHF from large L-to-R shunts (VSD most common), progressing to pulmonary hypertension and potentially Eisenmenger syndrome in rare long survivors [2][7]
- Neurological: Seizures (from HPE/cortical malformation), central apnoea (brainstem malformation — common proximate cause of death), profound ID (universal)
- Respiratory: Aspiration pneumonia (from swallowing dysfunction + cleft palate) is the most common respiratory complication and a major cause of morbidity/mortality
- Renal: Progressive renal failure from structural anomalies; UTIs from urinary tract malformations
- Ophthalmological: Functional blindness from cumulative effect of microphthalmia, retinal dysplasia, coloboma, congenital cataract [2][4]
- Feeding / growth: Failure to thrive is universal due to multifactorial feeding difficulty + ↑metabolic demand
- Omphalocele post-op: Monitor for abdominal compartment syndrome [5]
- Psychosocial: Parental grief, sibling impact, financial burden — the whole family is the patient
- Most infants die from cardiopulmonary failure or central apnoea within the first month of life
Silver-russell Syndrome
Silver-Russell syndrome is a congenital growth disorder presenting in infancy and early childhood with intrauterine and postnatal growth restriction, relative macrocephaly, a triangular face, body asymmetry, and feeding difficulties, most commonly caused by hypomethylation at chromosome 11p15 or maternal uniparental disomy of chromosome 7.
Edward Syndrome (trisomy 18)
Edward syndrome is a severe chromosomal disorder caused by an extra copy of chromosome 18, typically presenting at birth with characteristic features including clenched fists with overlapping fingers, rocker-bottom feet, cardiac defects, and profound developmental disability, with most affected infants dying within the first year of life.