Down syndrome

What it is

Down syndrome is trisomy 21. It is the most common trisomy, with trisomy 18 second after it. It is also named the most common overall cause of mental delay, and that cause is not inherited; the most common inherited cause is Fragile X syndrome.

Causes and risk

Three modes are given. Non-disjunction is the commonest. The second listed is Robertsonian translocation, usually onto 14: when one parent is a balanced translocation carrier with both copies of chromosome 21 fused together, recurrence is 100%. The third listed is mosaicism.

How it presents

After birth the physical examination shows characteristic facial features, hypotonia, single palmar crease and sandal gap toe. Other clinical features named are a small head (microcephaly), a small mouth (microstomia) and a small mandible (micrognathia), with congenital cataract written beside the broad flat face. The anomalies that go with the condition are CHD, duodenal atresia and Hirschsprung disease. The most common CHD is atrioventricular septal canal defects, at 40%.

Up to 10% of children with Down syndrome have Hirschsprung disease, which occurs in 1 in 5000 live births and is the result of aberrant migration of neural crest cells during colonic development. Ninety-four percent of neonates with Hirschsprung do not pass meconium within 24 hours of birth, and the other symptoms at presentation are vomiting, abdominal distension and enterocolitis. The picture that makes Hirschsprung disease most likely is an infant with trisomy 21 who passed meconium only at 72 hours of life after rectal stimulation, has had no further bowel movement, has a distended but soft abdomen with appropriate bowel sounds and has been spitting up after feeds, and whose rectal examination shows a normally placed anus with a tight anal canal. The three clues are the trisomy 21, the delayed passage of meconium and the tight anal canal.

Trisomy 21 also carries a higher risk of a duodenal web, and the two are told apart on rectal examination: vomiting is the key symptom of a web, but a web should not give a tight anal canal or delayed passage of meconium. Milk protein intolerance can be associated with vomiting and constipation in infants, but delayed passage of meconium would not be expected and the rectal examination should show normal tone. Cystic fibrosis may present with constipation or even a small bowel obstruction from meconium ileus, but again the rectal examination should not be abnormal.