A girl with an inherited central deletion 22q11.21 resulting in DiGeorge syndrome without typical congenital anomalies

Abstrakt

Introduction: Central deletions 22q11.21 are quite rare, only limited numbers of individuals have been reported. Deletions are nested at the distal end of the most common ~3 Mb region resulting in DiGeorge (DGS)/velocardiofacial syndrome but do not contain the DGS critical genes HIRA or TBX1.

These "atypical" deletions exhibit a highly variable clinical phenotype. They are challenging to recognize, share many features with the "typical" DGS and show high level of inheritance.

Case presentation: Here we present a 9-year old girl referred to genetic counselling for inflammatory bowel disease and short stature. Array CGH analysis was performed and identified a deletion in 22q11.21 region located between low copy repeats blocks LCR22-B and LCR22-D, spanning 35 genes including CRKL.

Neither TBX1 nor HIRA were deleted. This same microdeletion was detected in apparently phenotypically normal father who has a history of recurrent infections and basaliomas.

Conclusions: Patients with DGS may not be severely affected. Sometimes it is hard to recognize their phenotype.

Clinical features of DGS are in general milder in related family members than in de novo cases. Affected parents can demonstrate extremely mild phenotype or no features at all.

Due to mild demonstration of clinical features numbers of affected individuals remain undiagnosed.