[Hirsutism. Two familial cases of 21-hydroxylase deficiency]

One to six percent of women with hirsutism have 21-hydroxylase deficiency. Beyond these classical congenital forms, the most frequent cases present non-specific signs of hyperandrogenism. The diagnosis of the deficiency is based on 17-hydroxy-progesteron (17-OHP) assay before and after ACTH stimulation.

We observed 2 sisters with a non-classical deficiency in 21-hydroxylase. Their phenotypes were very different: the elder sister had severe hirsutism and clitoromegaly and was overweight; the younger sister had more moderate hirsutism with no other signs of hyperandrogenism. Hormone patterns were also different. Both baseline and stimulated plasma 17-OHP were higher in the elder sister (47 ng/ml to 126 ng/ml and 5.2 ng/ml to 42.8 ng/ml respectively). The genotype was however identical. Both were homozygous for CYP21A duplication and short C4B and had a Val281Leu mutation on exon 7 of the CYP21B gene.

This phenotypic variability in subjects with the same genotype could be explained by increased sensitivity to androgens or, more likely, to the presence of currently undetectable mutations. Genetic counselling is often requested due to the high frequency of non-classical forms and the large number of heterozygous subjects with the 21-hydroxylase trait. It is thus important to screen for 21-hydroxylase deficiency in women with hirsutism. In addition, molecular assessment of CYP21B gene should be proposed for all subjects with a non-classical form as well as family members (at least the father and mother).