One missing sliver of chromosome 22 can affect the heart, immunity and speech
DiGeorge syndrome comes from losing a tiny stretch of chromosome 22, taking 30 to 50 genes with it. That single gap can cause heart defects, a weak immune system, a cleft palate and learning difficulties, and it raises schizophrenia risk twenty- to thirtyfold. About 1 in 4,000 people carry it.
The American physician Angelo DiGeorge described the condition in 1968, and its genetic basis was worked out in late 1981. Doctors now often call it 22q11.2 deletion syndrome, after the address of the missing segment on the chromosome's long arm; in most patients the gap spans about 3 million base pairs. Around 90 per cent of cases arise fresh during early development rather than being inherited, because this region's structure makes it unusually prone to rearranging when sperm or eggs form. A French study of 749 patients found inheritance in 15 per cent of cases, mostly through the mother. Only one affected copy is needed.
Symptoms vary widely, even within one family. An old teaching mnemonic, CATCH-22, groups the classic features: heart abnormalities, distinctive facial features, and low calcium from underactive parathyroid glands, among others. A newborn may first come to attention through a heart defect or seizures caused by low calcium. Frequent infections stem from an absent or underdeveloped thymus, the gland that trains T cells.
Speech is often hit hard. About 69 per cent of children have palate abnormalities that let air leak through the nose while talking, and many rely on sounds made at the front or back of the mouth, such as glottal stops, because consonants formed in the middle are missing. Vocabulary can be severely delayed, though speech tends to improve with age. Most children score below the borderline of normal on IQ tests, usually doing better on verbal than non-verbal tasks.
Researchers suspect one gene in particular, TBX1, which helps build tissues from the neural crest, the embryonic cells that form parts of the face, the heart's outflow tract and the thymus; mice lacking it develop similar artery and thymus defects. In adulthood about a quarter develop schizophrenia, and early Parkinson's disease is also more common, sometimes diagnosed up to 10 years late because antipsychotics can mimic its symptoms. There is no cure, but with treatment across the affected organs life expectancy may be normal.
Source: DiGeorge syndrome
