Presentation: Clinical suspicion of Patau syndrome (trisomy 13)

A baby is admitted to the neonatal intensive care unit (NICU) after birth. Antenatal scans had shown intrauterine growth restriction (IUGR), an atrial septal defect and bilateral extra fingers. The parents had declined amniocentesis. The baby has distinctive physical features suggestive of Patau syndrome, including close set eyes, cutis aplasia, clenched hands and unusually shaped feet with prominent heels.

Patau syndrome can present in a variety of ways.

• Prenatally: Most cases are identified at this stage. Many parents opt to have screening for Patau syndrome, and signs are typically evident on prenatal ultrasounds. For more information, see Patient with a higher-chance first-trimester combined screening result, Fetus with raised nuchal translucency and Patient with a higher-chance non-invasive prenatal test result.
• Postnatally: Neonates may present with IUGR and typical physical features. There are also numerous medical conditions that are more common in the context of Patau syndrome. Signs and symptoms are listed below.
• 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 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.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient or family. It may be appropriate to select more than one.
  • R26 Likely common aneuploidy. This is the correct test if you are reasonably confident that the patient has Patau syndrome. The common aneuploidy (QF-PCR) test looks for the presence of trisomy 13, trisomy 18, trisomy 21 and Turner syndrome. Note that this test request indication does not include gene sequencing. If a negative result is returned, further genomic testing may be indicated.
  • R137 Congenital heart disease (microarray). You may request R137 if you are investigating a chromosomal cause for congenital heart disease that may include Patau syndrome. Note that this test request indication does not include gene sequencing. If a negative result is returned, further genomic testing may be indicated.
    • See: Infant or child with congenital heart disease.
  • R27 Paediatric disorders. This should be considered if there is developmental delay or intellectual disability in association with congenital malformation or overgrowth, and you would like to investigate chromosomal and single-gene causes. The test is a whole genome sequencing (WGS) ‘super-panel’ (a panel comprised of several different constituent panels forming one large panel).
  • R14 Acutely unwell children with a likely monogenic disorder. This may be considered in the context of an acutely unwell infant with multiple congenital anomalies and a normal R26 result, where a diagnosis may change management. Both parents should be available for trio analysis, though occasional exceptions may be made. R28 Congenital malformation and dysmorphism syndromes (microarray only) may also be undertaken in parallel.
  • R265 Chromosomal mosaicism (karyotype). A minority of individuals with Patau syndrome have some cells with trisomy 13 and some cells with the usual two copies of chromosome 13. This is termed mosaicism. R265 can be requested when R26 is suggestive of mosaicism, or if the clinical features are highly suggestive of Patau syndrome but R26 returns a negative result.
  • R297 Possible structural chromosomal rearrangement (karyotype). This should be considered if findings from microarray, WGS or other laboratory techniques suggest a possible Robertsonian translocation, reciprocal translocation, ring chromosome or other microscopically visible structural rearrangement. This is also the test indication you would use for parents of an affected child when a karyotype from the child indicates a Robertsonian translocation, because parental karyotypes are essential in determining the recurrence risk. (If a parent is a carrier of a Robertsonian translocation between chromosomes 13 and 14, the risk of the couple having live-born offspring with Patau syndrome is under 1% and the risk of uniparental disomy of chromosome 14 is 0.5%.)
• For tests that are undertaken using WGS, including R27, you will need to:
  • complete an NHS GMS test order form with details of the affected child (proband) and their parents, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support in completing WGS-specific forms);
  • complete an NHS GMS record of discussion (RoD) form for each person being tested – for example, if you are undertaking trio testing of an affected child and their parents, you will need three RoD forms (see How to complete a record of discussion form for support); and
  • submit parental samples alongside the child’s sample (this is trio testing) to aid interpretation, especially for the larger WGS panels (where this is not possible, for example because the child is in care or the parents are unavailable for testing, the child may be submitted as a singleton).
• For tests that do not include WGS, including R26, R28, R137, R265 and R297:
  • you can use your local Genomic Laboratory Hub test order and consent (RoD) forms; and
  • parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• The majority of tests are DNA-based, and an EDTA sample (purple-topped tube) is required. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (green-topped tube).
• R27 is a large WGS super panel, and requesting it currently requires authorisation from clinical genetics.
• R14 is a WGS test that looks agnostically across the entire genome. Requesting it currently requires authorisation from clinical genetics. There is a special test order form and RoD form for this test, which are available from the Exeter Genetics Laboratory.

Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NHS England: National Genomic Test Directory
• Soft UK: Healthcare professionals

For patients

• NHS England: Whole genome sequencing patient information leaflets
• Sands (support for anyone who has been affected by the death of a baby)
• Soft UK (support for families of children born with trisomy 13 or trisomy 18)
• Together for Short Lives (support for families of seriously ill children)
• Trisomy 18 Foundation