Background: NR5A1 mutations in 46,XY patients lead to various degrees of disorders of sex development (DSD). Familial cases have been described where the mother (heterozygous for the mutation) presented primary ovarian failure. Little is known about testicular function at puberty but most patients have biological markers of gonadal dysgenesis, raising fears of infertility.
Objective and hypotheses: To describe a familial form of DSD due to NR5A1 mutation transmitted by the affected father.
Method: Case report.
Results: The index case presented at birth a 25 mm penis with perineal hypospadias and bifid scrotum containing two testis. At minipuberty (7 weeks), the hormonal exploration showed: testosterone=3.42 nmol/l with normal precursors, LH=7.3 UI/l, FSH=3.3 UI/l, AMH=475 pmol/l. After hCG test (six injections of 1500 U every 2 days), testosterone raised to 4.9 nmol/l and AMH decreased during childhood (209 pmol/l at 4 years) suggesting partial testicular dysgenesis. He needed testosterone therapy for increasing penile length and hypospadias surgery. The right testis was brought down at 4 years for secondary ascension. His father presented a perineal hypospadias operated during the childhood but no micropenis. Puberty occurred spontaneously and he had no testosterone treatment. His wife became twice pregnant without medical assistance. At 35 years, leydig function was normal (testosterone=17 nmol/l, LH=4 U/l) but FSH and inhibin B suggested a partial balanced Sertoli dysfonction (Inhibine B=85 nmol/l, FSH=10 UI/l). Father and son were heterozygous for c.269delG mutation of NR5A1. They had no adrenal insufficiency.
Conclusion: NR5A1 mutations may be transmitted by the affected father. Gonadal dysgenesis is variable and spontaneous puberty and fertility is possible in some cases.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology