[Premature androgenetic alopecia in adult male with nonclassic 21-OH deficiency. A novel nonsense CYP21A2 mutation (Y336X) in 2 affected siblings]. / Alopecia androgénica prematura en un varón con déficit de 21-hidroxilasa no clásico. Nueva mutación grave (Y336X) del gen CYP21A2 en 2 hermanos afectados.

BACKGROUND AND OBJECTIVE: 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. PATIENTS AND METHOD: Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia. RESULTS: Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X). CONCLUSIONS: 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.

Alopecia androgénica prematura en un varón con déficit de 21-hidroxilasa no clásico. Nueva mutación grave (Y336X) del gen CYP21A2 en 2 hermanos afectados / Premature androgenetic alopecia in adult male with nonclassic 21-OH deficiency. A novel nonsense CYP21A2 mutation (Y336X) in 2 affected siblings

Fundamento y objetivo: La hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa en su forma no clásica se manifiesta por síntomas y signos de hiperandrogenismo, que suelen ser evidentes en la mujer, pero pueden no serlo en el niño y adolescente, y que rara vez se reconocen en el varón adulto. La alopecia androgénica en el varón se considera un síntoma andrógeno y dependiente de la edad, pero su aparición temprana debe hacer sospechar un trastorno endocrinológico y obliga a realizar el estudio bioquímico correspondiente. Pacientes y método: Se presenta el caso de 2 hermanos (mujer y varón) en quienes el motivo de consulta del varón fue la alopecia prematura. Resultados: El estudio molecular del gen CYP21A2 detectó en ambos una mutación grave (Y336X), no descrita anteriormente, en heterocigosis compuesta con la mutación leve (V281L). Conclusiones: Dada la alta frecuencia de portadores de mutación grave en la población (1:60), se discute el riesgo de presentación de una forma clásica de la deficiencia en la descendencia de estos pacientes y la necesidad del diagnóstico molecular para el consejo genético

Background and objective: 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. Patients and method: Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia. Results: Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X). Conclusions: 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