Patau syndrome (trisomy 13)

Patau syndrome, or trisomy 13, is a life-limiting genetic condition in which there is an extra copy of chromosome 13 in all or some cells. Survival rates are low, and those babies born alive with Patau syndrome will have learning disabilities and a wide range of serious health challenges.

Prenatal

Some of the suggestive ultrasound findings for Patau syndrome are listed below.

• Intrauterine growth restriction, leading to low birth weight.
• Severe heart anomalies.
• Holoprosencephaly (the brain failing to divide into two parts during fetal development), which can be associated with:
  • cleft lip and palate;
  • atypically small eye or eyes (microphthalmia);
  • absence of one or both eyes (anophthalmia);
  • reduced distance between the eyes (hypotelorism); and
  • problems with development of the nasal passages.
• Other anomalies of the face and head include:
  • smaller-than-normal head size (microcephaly);
  • skin missing from the scalp (cutis aplasia);
  • ear malformations and deafness; and
  • raised, red birthmarks (capillary haemangiomas).
• Patau syndrome can also cause other problems, such as:
  • abdominal wall anomalies;
  • cysts in the kidneys;
  • small penis in boys; and
  • enlarged clitoris in girls.
• There may also be anomalies of the hands and feet, such as extra fingers or toes (polydactyly) and a rounded bottom to the feet, known as rocker-bottom feet.

Postnatal

Some of the signs and symptoms of Patau syndrome are listed below.

• Low birth weight and/or slow growth.
• Craniofacial features:
  • scalp anomalies, such as missing skin;
  • sloping forehead;
  • close-set eyes;
  • short, flat or atypically shaped nose;
  • cleft palate and/or lip;
  • small jaw; and
  • ears that may be small, low set, posteriorly rotated and malformed.
• Limb anomalies:
  • clenched hands;
  • single palmar crease;
  • extra fingers and toes (polydactyly);
  • nail hypoplasia;
  • smooth, curved sole of the foot with prominent heel; and
  • club feet.
• Cardiac anomalies (found in 80% of cases):
  • septal anomalies;
  • tetralogy of Fallot; and
  • double outlet right ventricle.
• Respiratory symptoms:
  • breathing difficulties, including apnoeas.
• Neurological symptoms:
  • microcephaly;
  • hypotonia and feeding difficulties;
  • seizures;
  • severe developmental delay;
  • alobar holoprosencephaly; and
  • spinal anomalies.
• Ophthalmological symptoms:
  • cataracts;
  • retinal dysplasia or detachment;
  • nystagmus;
  • optic nerve hypoplasia;
  • small or absent eyes; and
  • coloboma of the iris.
• Gastroenterological symptoms:
  • omphalocele;
  • umbilical hernia;
  • malrotation; and
  • Meckel diverticulum.
• Genital anomalies:
  • undescended testicles;
  • hypospadias;
  • hypertrophy of the clitoris;
  • labia minora hypoplasia; and
  • bicornuate uterus.
• Renal symptoms:
  • polycystic kidney;
  • hydronephrosis; and
  • horseshoe kidney.
• Other:
  • hearing loss; and
  • capillary haemangioma.

Individuals with Patau syndrome typically have a short life expectancy (more than 9 in 10 children die during their first year of life). There is a high rate of death in utero. Cardiopulmonary arrest and central apnoeas are leading causes of death in the neonatal period.

Gastro-oesophageal reflux and feeding difficulties are almost universal, and aspiration can lead to decompensation. Survival time is increased for infants treated intensively. Around 1 in 10 babies with less severe forms of the syndrome, such as partial or mosaic trisomy 13, live for more than a year.

Patau syndrome occurs in 1 in 5,000 live births (though it should be noted that these figures will be confounded by the numbers of pregnancy terminations). It usually arises when each cell has three copies of chromosome 13, rather than the usual two.

Mosaic Patau syndrome refers to the phenomenon in which an affected individual has three copies of chromosome 13 in some of their cells and two in other cells. Individuals with mosaic Patau syndrome tend to have milder features.

In up to 1 in 10 cases of Patau syndrome, genetic material is rearranged between chromosome 13 and another chromosome. This is called a chromosomal translocation. Features can vary depending on the level of mosaicism (the number of cells containing an extra copy of chromosome 13) and the tissues involved. This can be difficult to accurately determine, so the prognosis (though often milder) is more unpredictable.

Testing for Patau syndrome can be pre- or postnatal.

Prenatal screening and diagnosis

Screening for Patau syndrome – along with screening for trisomies 21 and 18 – is offered to all pregnant women in the first trimester, as part of the NHS Fetal Anomaly Screening Programme.

A separate pathway in the National Genomic Test Directory (R445) exists for individuals who have had a previous pregnancy or child diagnosed with full trisomy 13. See Pregnancy in which a previous pregnancy or child was diagnosed with trisomy 21, 18 or 13.

First-trimester screening

The combined first-trimester screening test is offered in the first trimester and uses maternal age, nuchal translucency measurement and blood tests (human chorionic gonadotropin (hCG) and pregnancy associated plasma protein-A (PAPP-A)) to calculate the chance of trisomy. The combined test can be performed in both singleton and twin pregnancies.

While the blood test can be taken from 10 weeks of pregnancy, nuchal translucency can only be measured when the fetal crown-rump length is between 45mm and 84mm (up to 14⁺¹ weeks’ gestation). For cases in which the nuchal translucency measurement is raised, please see Fetus with raised nuchal translucency.

If the patient’s chance of trisomy is found to be greater than or equal to 1 in 150, the patient is offered further testing as outlined below.

• Where a structurally normal fetus is seen on ultrasound imaging, this testing may be in the form of advanced screening with non-invasive prenatal testing (NIPT). See Patient with a higher-chance non-invasive prenatal test result.
• Where anomalies are seen on the scan, further investigation may take the form of cytogenetic testing, which would require an invasive procedure such as amniocentesis or chorionic villus sampling in order to obtain fetal or placental DNA.

For more information, see Pregnancy in which the mother has a higher-chance first-trimester combined screening test result.

The 20-week screening scan

As part of the NHS Fetal Anomaly Screening Programme, an ultrasound scan is offered to all pregnant women between 18⁺⁰ and 20⁺⁶ weeks to screen for 11 physical conditions, including Patau syndrome. Where unexpected scan findings are identified, women are referred to their local fetal medicine team for further discussions, detailed scanning and an offer of invasive testing where appropriate.

Postnatal diagnosis

Where a baby is born with clinical features suggestive of Patau syndrome (in the absence of a prenatal diagnosis), a blood sample may be taken for confirmatory diagnostic testing following discussion with and consent from the parents.

Patau syndrome usually arises spontaneously owing to an error in cell division. This is most commonly in the egg, but it occasionally occurs in the sperm. The chance increases with maternal age. Recurrence risk is usually low, though some couples may have an increased recurrence risk owing to parental germline mosaicism. This means that a patch of cells that includes the eggs or sperm has an extra copy of chromosome 13. It is very rare, but it should be considered in the context of two affected pregnancies. Referral to clinical genetics should be considered.

There is a 5% to 10% chance of a Robertsonian translocation. This is a structural rearrangement of the chromosomes in which one copy of chromosome 13 is attached to another chromosome, usually chromosome 14. Cases of Patau syndrome that arise from a translocation result in a different appearance on a karyotype, because the extra copy of chromosome 13 is attached to another chromosome. When this appearance is seen, parental karyotypes are essential to determine the recurrence risk. If this risk is highlighted in your patient’s family, consider a referral to clinical genetics.

Antenatal management

Where invasive testing has confirmed a diagnosis of Patau syndrome during pregnancy, the parents should be counselled regarding the nature of the condition and expected antenatal and postnatal management. The severity and subsequent predicted prognosis need to be explained. The options for both continuing the pregnancy and termination should be discussed.

For ongoing pregnancies, care should be delivered by a multidisciplinary team and involve midwifery, obstetrics, fetal medicine and paediatrics. Planning for pregnancy, labour and postnatal care should involve parents at all stages. Parents should also be signposted to the relevant charity for additional support and information.

Postnatal management

Management of children with Patau syndrome is complex; it requires sensitive counselling, discussions with the family and shared decision making.

Patient support charity SOFT UK provides some guidance about managing such conversations with families during both the antenatal and postnatal periods. For some patients, a palliative approach may be pursued; for others, more intensive interventions may be undertaken. Care should be delivered via a multidisciplinary team.

For clinicians

• Gov.uk: NHS Fetal Anomaly Screening Programme (FASP): Programme overview
• NHS England: National Genomic Test Directory
• SOFT UK
• StatPearls: Patau syndrome

References:

• Carey JC and Kosho T. ‘Perspectives on the care and advances in the management of children with trisomy 13 and 18‘. The American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2016: volume 172 issue 3, pages 249–250. DOI: 10.1002/ajmg.c.31527

For patients

• Antenatal Results & Choices
• Gov.uk: Screening tests for you and your baby (STFYAYB)
• Gov.uk: Your choices after a higher chance screening result
• NHS Health A to Z: Patau’s syndrome
• Sands
• SOFT UK
• Together for Short Lives