Patau's Syndrome

• Patau's syndrome (trisomy 13) carries a high mortality rate with multiple congenital abnormalities which result in severe physical and mental impairment.
• It is usually (80% of cases)¹ due to a freestanding trisomy with an extra number 13 chromosome, instead of the usual pair, in all cells.
• An unbalanced chromosome translocation can also occur, commonly a Robertsonian translocation. This is when an extra copy of chromosome 13 is attached to another chromosome.
• Rarely, structural chromosome abnormalities can occur where only part of chromosome 13 is duplicated.²
• There may also be mosaic variations in which some cells are normal with 46 chromosomes and others have the extra chromosome. Infants with mosaic variations tend to be less severely affected.

• Patau's syndrome is the least common and the most severe of the viable trisomies.²
• In liveborn infants, it is more likely that the affected infant is female rather than male. This is thought to be due to the fact that male fetuses with trisomy 13 are more likely to be lost due to miscarriage or stillbirth. This ratio continues as the infant ages, with females more likely to survive.²
• The incidence in live births is 1 in 21,700 and may be falling due to antenatal screening and selective termination of pregnancy.¹

• A personal or close family history of giving birth to an affected child increases the risk.
• Risk rises with increasing maternal age but not as markedly as with Down's syndrome (trisomy 21) or Edwards' syndrome (trisomy 18).^3,1

Many fetuses never survive until term and are stillborn or spontaneously abort.

Features include:

• Intrauterine growth retardation and low birth weight
• Congenital heart defects: occur in 80%; include atrial septal defect, ventricular septal defect, patent ductus arteriosus, dextrocardia
• Holoprosencephaly: the brain doesn't divide into two halves; can present with midline facial defects including:
  • Cleft lip and palate
  • Microphthalmia or anophthalmia
  • Nasal malformation
  • Hypotelorism (reduced distance between the eyes) or cyclops
• Other brain and central nervous system abnormalities including:
  • Neural tube defects
  • Other anatomical defects of the brain
  • Severe learning disability
  • Problems with control of breathing (central apnoea)
• Other craniofacial abnormalities include:
  • Microcephaly
  • Scalp defects (cutis aplasia: skin missing from the scalp)
  • Ear malformations and deafness
  • Capillary haemangiomata
• Gastrointestinal abnormalities: omphalocele, exomphalos, hernias
• Urogenital malformations: polycystic kidneys, micropenis or hypertrophy of the clitoris
• Abnormalities of hands and feet: polydactyly (extra fingers or toes), rocker-bottom feet

• Infants with Patau's syndrome and Edwards' syndrome can have similar features and be difficult to differentiate.
• Holoprosencephaly and polydactyly are more specific to trisomy 13, while clenched fingers and exomphalos are more common in trisomy 18.¹

• Cytogenetic studies and chromosomal analysis will confirm the diagnosis.
• Organ systems will need specific investigation depending on the abnormality, e.g. echocardiography for cardiac abnormalities, skeletal radiography etc.
• Treatment of a liveborn infant is generally supportive but life sustaining measures are not always carried out. Considerable thought and discussion is recommended before undertaking measures such as surgical correction of abnormalities. Nasogastric or gastrostomy feeding is feasible but it is questionable if this is prolonging life or prolonging death.
• Parents will need a great deal of support and counselling. Support organisations may be useful (see below).
• If Patau's syndrome is due to an unbalanced chromosome translocation or structural chromosome abnormality, both parents should undergo chromosomal analysis. It may be that the translocation in the infant occurred de novo but a balanced translocation may be found in one of the parents. This has significance for future pregnancies because of a higher risk of recurrence. Other family members may also be affected.
• Screening and/or prenatal diagnosis should be offered for future pregnancies. For full trisomy 13, the risk of recurrence is approximately 0.5% above the mother's age-related risk.² Risk may be higher if a parent carries a balanced translocation. Referral should be made to a geneticist as appropriate.

• Life expectancy is very limited. Median survival is 2.5 days.²
• However, when counselling parents, you should not tell them that the child will not survive as this may affect their decisions about whether to continue the pregnancy:
  • 1 in 20 survive longer than 6 months.²
  • Rarely, there can be survival into the teens.²
• Cardiopulmonary arrest, congenital heart disease and pneumonia are the most common causes of death.²
• Profound mental retardation and developmental delay occurs in survivors. Seizures and feeding difficulties are common.¹

• Specific ultrasound findings may suggest trisomy 13 and subsequent cytogenetic studies may therefore be indicated. Findings include:²
  • Increased nuchal translucency
  • Cardiac defects
  • Neural tube defects
  • Facial clefting
  • Renal abnormalities
  • Omphalocele
• A study from Kings College Hospital showed that at the 11 to 13(+6)-week scan, the measurement of fetal nuchal translucency and fetal heart rate and fetal examination for holoprosencephaly, exomphalos, and megacystis can identify > 90% of fetuses with trisomy 13.⁴
• First trimester multiple marker screening (that which is currently offered for Down's syndrome screening) may also help to identify a fetus with trisomy 13 or 18. Markers can include maternal age, nuchal translucency measurement, pregnancy-associated plasma protein A (PAPPA) and human chorionic gonadotrophin (hCG).² Ultrasound at that time may also show fetal anomalies.
• Second trimester screening tests can be offered if the mother presents later. Please refer to the article Antenatal Screening for Down's Syndrome for more details about second trimester screening tests.
• In a UK-based study from 2003, 44 cases of trisomy 13 and 88 cases of trisomy 18 were examined. 64% were first detected by chromosomal analysis because of abnormalities noted on fetal anomaly scanning in the second trimester. 3% of cases were detected through the serum screening programme currently offered for Down's syndrome. 11% of cases were detected post-natally. Of note, in the same study, 12% of couples chose to continue with the pregnancy after prenatal diagnosis.³

• Amniocentesis or chorionic villus sampling is needed to make a definitive prenatal diagnosis.
• Cytogenetic study of fetal blood may also be carried out.
• Mothers over the age of 35 may choose to go straight to diagnostic testing. Others mothers may choose to have diagnostic testing after a positive screening test.

• Klaus Patau was a German-born, American, human geneticist. Patau et al described the syndrome in 1960,⁵ the same year that Edwards et al described trisomy 18.⁶
• In the same year, Patau was the second name on a paper by Smith et al that also described trisomy 18.⁷
• The clinical appearance of trisomy 13 was first described by Erasmus Bartholin in 1657 but he was unaware of the aetiology.