[Premature androgenetic alopecia in adult male with nonclassic 21-OH deficiency. A novel nonsense CYP21A2 mutation (Y336X) in 2 affected siblings]

Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency mainly manifests with symptoms and signs of hyperandrogenism, which are usually obvious in women and sometimes obvious in children or adolescents, but are rarely observed in adult men especially with increasing age. Male pattern alopecia is considered an androgenetic and age-related symptom. However, its early appearance should raise the suspicion of an underlying endocrinological disease, and biochemical screening should be done.Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia.Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X).Given the high prevalence of carriers with severe mutations, we discuss the risk for such patients of conceiving a child with a classical disease and the need for a reliable molecular diagnosis in order to provide accurate genetic counselling.