Distal 22q11.2 microdeletion syndrome

Distal 22q11.2 microdeletion syndrome (Orphanet code 261330) is a rare chromosomal disorder caused by a microdeletion in the distal portion of the 22q11.2 region, distinct from the more commonly known proximal 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome). The deleted region is located telomeric (distal) to the typical DiGeorge syndrome critical region and encompasses different genes, leading to a partially overlapping but distinct clinical presentation. The syndrome affects multiple body systems. Key clinical features include prenatal and postnatal growth restriction, developmental delay, intellectual disability of variable severity, and speech and language delays. Affected individuals may present with congenital heart defects, skeletal anomalies, and mild dysmorphic facial features. Some patients exhibit behavioral difficulties, including features on the autism spectrum. The phenotype is highly variable, even among individuals with similar-sized deletions, and some carriers may be only mildly affected or apparently asymptomatic, which can complicate diagnosis. There is no specific cure for distal 22q11.2 microdeletion syndrome. Management is supportive and symptom-based, involving a multidisciplinary team. This may include early intervention programs for developmental delays, speech therapy, cardiac evaluation and surgical correction of heart defects if needed, orthopedic management for skeletal issues, and behavioral or psychological support. Genetic counseling is recommended for affected families, as the deletion may be inherited from a mildly affected parent or arise de novo. Diagnosis is typically confirmed through chromosomal microarray analysis (array CGH) or fluorescence in situ hybridization (FISH).

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