Familial male-limited precocious puberty in neurofibromatosis type I

Precocious puberty in patients with neurofibromatosis type 1 (NF-1) is predominantly central in origin, with intracranial pathologies like optic glioma. We describe one patient with NF-1 who presented with precocious puberty with the eventual diagnosis of familial male-limited precocious puberty and share the potential pitfalls. He presented at 7 years of age with growth spurt and pubertal genitalia development with enlarged testicular volume of 7 mL, but LHRH stimulation test revealed blunted luteinizing hormone and follicle-stimulating hormone peak suggestive of a peripheral cause, contrary to the expectation due to the background of NF-1. Testosterone level was elevated with bone age advancement by 2 years. Genetic analysis revealed a previously reported heterozygous missense mutation of the luteinizing hormone/choriogonadotropin receptor gene Ala572Val. His father was also heterozygous for the same mutation but was apparently asymptomatic and not short.

Our report illustrates two potential pitfalls in the clinical evaluation of patients with familial male-limited precocious puberty (FMPP). Firstly, patients with FMPP will have mild to moderately enlarged testes and should not be wrongly diagnosed as central precocious puberty without the gonadotropin-releasing hormone stimulation test. Secondly, family members with the same mutation may have different phenotypic severities, where some male carriers may have subtle features.