Non-conventional Genetic Basis of Congenital Adrenal Hypoplasia in South Asia

Congenital adrenal hypoplasia or adrenal hypoplasia congenita (AHC) is a rare disorder ascribed to mutations in three genes, namely, the dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1/NROB1 gene), steroidogenic factor-1 gene (SF-1/NR5A1 gene), and Achalasia-Addisonianism-Alacrima syndrome gene (AAAS gene). Five cases of AHC of local South Asian origin are described here. Golden Helix VarSeq 2.2.0 (Golden Helix Inc., Bozeman, MT, United States), the clinical genomics interpretation and reporting platform, was used for genetic study. No subject had congenital adrenal hyperplasia (CAH). Four male neonates presented with hypoglycemia, and one older female child presented with hyperpigmentation. This girl had a recognized mutation in the AAAS gene, while none of the four male neonates had any of the recognized mutations associated with AHC. Further, none were salt-losing, which is the conventional Western phenotype. Thus, additional, yet unknown, gene(s) must be operative in AHC among South Asian subsets.