22q11.2 deletion syndrome

A neonate in the intensive care unit is grunting and duset at twenty-four hours of age, the duct-dependent heart closing in front of you; or a new baby is seized, and the ionised calcium is undetectable; or a three-year-old speaks through her nose, catches every virus at preschool, and carries a repaired tetralogy of Fallot on her chart. The fellowship task is to see that each of these is the same chromosome, to send the test that will find it, and to lay a surveillance net across heart, calcium, palate, immunity, development, and mental health before any one of them causes harm. ^{[1] [11]}

Overview & Definition

A baby born with a hemizygous loss of genetic material at chromosome 22q11.2 carries the most common recurrent microdeletion in humans, and the phenotype that follows is so variable that it gathered a handful of eponyms before the molecular unification. What Angelo DiGeorge described in the 1960s as congenital absence of the thymus and parathyroids, Robert Shprintzen later called velocardiofacial syndrome for the cleft palate, cardiac defect, and characteristic face, and cardiologists labelled the conotruncal anomaly face syndrome. Each is the same deletion, and the modern name — 22q11.2 deletion syndrome — is the one that unifies them and sets the genetic counselling. ^{[1] [11]}

The deletion removes around 30 to 40 genes, and the loss of a single one — TBX1, a transcription factor that patterns the third and fourth pharyngeal arches and pouches — accounts for the cardiac, thymic, parathyroid, palatal, and facial features. Expressivity is wildly variable and penetrance incomplete, so the same deletion can produce a neonate with complete DiGeorge syndrome and an adult whose only clue is a repaired heart lesion and a late diagnosis of schizophrenia. That variability is the central teaching point: the microdeletion is the unifying fact, but the patient in front of you is one point on a wide spectrum. ^{[1] [3]}

The lifespan task has shifted as survival has improved. A generation ago the diagnosis centred on the neonate with severe immunodeficiency or a complex heart; today the population includes school-age children with learning differences, adolescents with emerging anxiety, and adults living with thyroid disease, arthritis, and psychiatric illness. The general paediatrician sits at the centre of this trajectory, coordinating cardiology, immunology, cleft and craniofacial surgery, endocrinology, and psychiatry from diagnosis to transition. ^{[1] [4]}

References12ShowHide

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2. [2]Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr, 2011.PMID 21570089
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