Missed diagnosis: 22q11.2 deletion syndrome

July 1, 2010

(PhysOrg.com) -- An article published in the June issue of the journalNature Reviews: Neuroscience provides one of the first comprehensive overviews of the genetic, neural and cognitive bases of a frequently undiagnosed congenital disorder with an array of complex genetic, medical, neurological, behavioral and psychiatric features: the often baffling chromosome 22q11.2 deletion syndrome (22q11.2DS).

Those with 22q11.2DS can display a panoply of congenital heart and oral/palatal/facial defects, other medical problems, intellectual disabilities and psychiatric disorders, so it often is mistaken for other conditions, said Tony Simon, a professor of psychiatry and behavioral sciences at the UC Davis MIND Institute and an author of the article.

"There is such a huge variation in the manifestation of 22q11.2DS that few physicians recognize it for what it is," Simon said. "But it's important that doctors be more aware of it so children can receive early identification services and management for each of the problems that may develop."

The condition's name describes a location on the 22nd chromosome, where a tiny bit of genetic information is missing: a microdeletion. The submicroscopic loss of DNA affects expression of some 35 to 60 genes. While it can be inherited, the mutation usually arises spontaneously. It is diagnosed using a test called fluorescence in situ hybridization.

Among the first to encounter children with 22q11.2DS may be pediatric cardiologists, because many children with the disorder are born with serious heart defects that require surgery at birth. Among these is tetralogy of Fallot, which occurs in nearly one quarter of people with 22q11.2DS. The defect, a complex of four heart malformations, is the most common cause of "blue baby" syndrome.

Abnormalities in the development of the palate and surrounding throat structures also are common in the disorder, as are facial abnormalities, learning disabilities, low calcium, thyroid and parathyroid levels, low muscle-tone and short stature. Immune-system abnormalities can make it dangerous for many affected children to receive certain live vaccinations.