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.
Conclusion: 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.