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Definition: Autosomal trisomy due to the presence of an extra whole chromosome 13 with a characteristic set of major congenital anomalies.
1. Overview
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Patau syndrome (trisomy 13) is caused by an additional chromosome number 13.
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Median survival for trisomy 13 is 8.5 days.
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Produces a recognisable constellation of both minor and major congenital abnormalities
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Associated with significant morbidity and mortality
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In those that survive there is profound physical and cognitive impairment
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Associated with increased maternal age
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Maternal age (years) |
Trisomy 13 (rate per 1000) |
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35 |
0.2 |
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36 |
0.3 |
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37 |
0.4 |
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38 |
0.5 |
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39 |
0.8 |
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40 |
1.1 |
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41 |
1.5 |
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42 |
2.1 |
Maternal age and Trisomy 13 found at amniocentesis (rate per 1000)
Based on Ferguson-Smith MA (1983). British Medical Journal 39 pp 355-364
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Incidence in live births is 1 in 21,700.
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Trisomy 13 should always be considered in a child with holoprosencephaly and multiple anomalies.
2. Inheritance
The majority of cases (80%) are due to non-disjunction of chromosomes in meiosis, where the affected child will have a third complete chromosome 13, and the extra copy of chromosome 13 is usually of maternal origin. The recurrence risk for the non-disjunction form is within the region of 1-2%. In the non-disjunction from of trisomy 13, there is no indication to carry out parental chromosome analysis.
Approximately 20% of cases can be due to an unbalanced chromosomal translocation, usually involving a Robertsonian whole chromosome translocation between chromosomes 13 and 14, which is clinically indistinguishable from the non-disjunction form. Parental chromosome analysis should be offered where trisomy 13 is due to an unbalanced translocation.
The translocation form of Trisomy 13 may be de novo (have arisen in the affected child for the first time in the family) or may be present in a balanced form in one of the parents. If one or other parent carries a balanced Robertsonian translocation involving chromosome 13, the recurrence risk would be significantly higher than that for non-disjunction. Prenatal testing could be offered in future pregnancies.
Mosaicism, where there is a mixture of cells in the affected baby, some with two chromosomes 13, and some with three chromosomes 13, also exists and may have a milder phenotype, depending on the degree of mosaicism. There are only about 30 cases of mosaic trisomy 13 reported in the literature worldwide.
3. Features – signs, symptoms & complications
Clinical Features
The severity of the features can be variable. Typical features include:
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Prenatal growth failure causing intrauterine growth retardation
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Craniofacial abnormalities
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Cleft lip and palate
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Other orofacial clefts
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Microphthalmia/anophthalmia
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Hypotelorism and occasionally cyclops (fused eyes)
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Prominent nasal bridge and tip
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Capillary haemangioma of forehead
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Ear malformations
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Vertex scalp aplasia
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Congenital heart defects (commonly VSD and ASD)
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Gastrointestinal abnormalities (exomphalos, malrotations)
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Urogenital abnormalities (cystic kidneys, enlarged lobulated kidneys)
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Pancreatic dysplasia
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Postaxial polydactyly (extra 5th fingers/toes)
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Brain abnormalities (holoprosencephaly, , absent corpus callosum, septum pellucidum and fornicies, cerebellar malformations)
Complications
Complications are related to the congenital abnormalities eg; congenital heart disease and brain malformations. Even those without severe congenital anomalies have a markedly reduced life expectancy. It is thought central apnoea contributes to mortality.
The median life expectancy for liveborn infants is 8.5 days (range 1 to 412 days).
3% are still alive at six months, but 80% will die within the first month. Several children have survived into adulthood but with profound physical and mental retardation, with a mental age at or below six months.
Seizures, deafness and blindness are common, as are feeding difficulties.
Some report behavioural problems including self mutilation.
4. Diagnosis
a. Differential diagnosis
If the cardinal features of orofacial clefts, holoprosencephaly, microphthalmia/anophthalmia and postaxial polydactyly are present diagnosis is relatively easily made clinically.
If abnormalities are subtle clinical diagnosis may be difficult and therefore definitive diagnosis relies on cytogenetic tests.
Trisomy 13 (Patau syndrome) has some features in common with trisomy 18. However there are certain features seen in trisomy 13 which are more specific eg; holoprosencephaly and polydactyly. exomphalos, severe growth retardation and clenched fingers seen more commonly in trisomy 18.
Differential diagnoses include:
· Meckel Gruber syndrome (renal abnormalities and encephalocele)
· Pseudotrisomy 13 (Holoprosencephaly syndrome)
· Pallister Hall sydrome
· Smith-Lemli-Opitz syndrome
These and other monogenetic syndromes should be considered where there is holoprosencephaly, cardiac malformations and polydactyly, but normal chromosomes.
Diagnostic testing using cytogenetic techniques will confirm the diagnosis of trisomy 13.
b. Direct diagnostic testing
Definitive diagnosis is by detection of a complete or partial trisomy of chromosome number 13.
Chromosome analysis can be carried out by fluorescent in situ hybridisation (FISH) studies on nuclei from uncultured cells, which gives a rapid result. An abnormal result occurs with the existence of three signals from chromosome 13, rather than two. A negative result however is not completely reassuring and the result from analysis of cultured cells should be awaited before confirming or excluding the diagnosis.
Chromosome analysis can be carried out prenatally on the fetus following chorionic villus sampling or amniocentesis. Amniocentesis can be offered to women of an older age (usually over 35-37 years) due to the known increased risk of chromosomal abnormalities. In others a high composite risk for Down syndrome may have been identified following routine antenatal blood testing or an anomaly scan has revealed a/or several fetal abnormalities, following which amniocentesis is offered.
c. Screening
Increasingly trisomy 13 is diagnosed antenatally at 10-14 weeks gestation by a combination of maternal age, nuchal thickness ultrasound and fetal anomaly scanning.
Antenatal screening: screening maternal blood test carried out at 16 weeks gestation may show an increased risk, although this test is more sensitive for trisomy 21. Detailed anomaly ultrasound scanning at 20 weeks may identify congenital malformations. Abnormalities in either of these screening techniques should be followed by the offer of further testing, such as amniocentesis.
5. Management
a. Treatment
Due to the significant morbidity and mortality of this condition management is supportive. It is generally seen as not appropriate to aggressively treat these babies, for example heart surgery, as life expectancy is limited and morbidity from other features of the disease are also present. Surviving infants should be followed up by a paediatrician.
Diagnosis should be made as soon as possible to avoid inappropriate intervention.
If a fetus is diagnosed antenatally and the parents wish to continue with the pregnancy the necessary measures should be in place so that the birth is dealt with appropriately eg; following discussion with obstetrician, paediatrician/neonatologist.
For those that do survive the following issues need to be addressed following discussion between care providers and the parents. This would also apply to those who are mosaic for trisomy 13.
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Feeding Difficulties
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Tube feeding, including teaching parents.
Gastrostomy
Treatment of Gastro-oesphageal reflux, which can cause recurrent pneumonia
Growth monitoring and plotting on modified growth charts and referral to a dysphagia team. |
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Development and Behaviour |
Referral to a Child Development Unit for developmental evaluation |
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Neurological |
Seizures tend to be well controlled on medication. Central apnoea can occur, particularly if holoprosencephaly is present and may be the cause of death. |
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Cardiovascular |
80% have congenital heart disease, cardiology assessment as soon after birth as possible is important, surgery is often withheld due to the general poor prognosis |
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Ophthalmology |
More than 50% have microphthalmia or anophthalmia, also retinal dysplasia, persistent hypoplastic primary vitreous with cataracts and corneal opacities. Ophthalmology review for all those who survive above one year is important as acuity problems are common. |
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Gastrointestinal/Genitourinary |
Surgical review of exomphalos and malrotation. Surgical intervention may be considered in a baby to aid supportive care if no severe heart defect is present, this may allow the parents to take the baby home. Ultrasound scanning of the renal tract should be performed as renal abnormalities may be present. Urinary tract infections are common. |
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Musculoskeletal |
Problems include polydactyly, limb reduction defects, talipes and contractures. Xrays should be performed with referral to an orthopaedic team. |
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Respiratory |
Pulmonary hypertension may occur. In those that survive and go home, home monitoring and oxygen therapy may be considered following discussion with parents. |
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Auditory |
There may be middle ear and temporal bone abnormalities, moderate to severe sensory neural hearing loss. Structural microtia and meatal atresia. In those who survive over six months an audiology assessment should be performed. |
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Neoplasia |
There is no strong association with neoplasia as there is with trisomy 18. There has been one reported case of Wilm’s tumour but this does not constitute a need for screening. |
b) Genetic counselling
If trisomy 13 is diagnosed antenatally couples should be offered the opportunity to discuss the findings with a clinical geneticist or genetic counsellor. It is important to stress that although life expectancy is poor, 3% are still alive at six months and a small number leave beyond one year. Those that do survive have developmental function limited to a six month level. This information may be important when parents are deciding whether to terminate or continue a pregnancy.
As with other trisomies the recurrence risk, following non-dysjunction, is in the region of 1% for trisomy 13, and can be influenced by maternal age in subsequent pregnancies. With increasing maternal age the risk of trisomy 21 will be greater than the risk of a recurrence of trisomy 13.
Parental chromosome analysis should be offered where trisomy 13 is due to an unbalanced translocation.. A de novo translocation in the infant would suggest a low recurrence risk for future offspring. If a balanced translocation is found in a parent the recurrence risk would be significantly higher. This would depend on the nature of the balanced translocation, and the sex of the carrier parent.. Prenatal testing can be offered in future pregnancies and other family members at risk should be alerted to their potential risk of also carrying the balanced form of the translocation.
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