Xp21 deletion syndrome

Xp21 deletion syndrome, also known as contiguous gene deletion syndrome involving the Xp21 chromosomal region, is a rare genetic condition caused by deletions of varying size on the short arm of the X chromosome at band p21. Because multiple genes located in close proximity are deleted together, affected individuals can present with a combination of several distinct conditions, including Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GKD), adrenal hypoplasia congenita (AHC), ornithine transcarbamylase deficiency (OTC deficiency), and intellectual disability. The specific combination and severity of features depend on the size and exact location of the deletion. The syndrome primarily affects males, as it follows an X-linked pattern of inheritance. Key body systems involved include the musculoskeletal system (progressive muscle weakness and wasting due to DMD), the endocrine system (adrenal insufficiency from AHC, which can present as life-threatening adrenal crises in the neonatal period), and the metabolic system (hyperglycerolemia from GKD and hyperammonemia from OTC deficiency). Neurological involvement, including intellectual disability and developmental delay, may also be present depending on the genes affected. Affected boys typically present in infancy or early childhood with symptoms such as failure to thrive, salt-wasting adrenal crises, elevated creatine kinase levels, and motor developmental delays. Treatment is supportive and directed at each component condition. Adrenal insufficiency requires lifelong glucocorticoid and mineralocorticoid replacement therapy, with stress dosing during illness. Duchenne muscular dystrophy is managed with corticosteroids, physical therapy, cardiac monitoring, and respiratory support. Glycerol kinase deficiency may require dietary management, and OTC deficiency, if present, is treated with protein restriction and nitrogen-scavenging medications. Early diagnosis through genetic testing, including chromosomal microarray or FISH analysis, is critical for timely initiation of appropriate therapies and surveillance. Genetic counseling is recommended for carrier mothers and at-risk family members.

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