Spontaneous Puberty in a Male with Heterozygous PROK2 Gene Mutation Presenting with Micropenis and Synkinesis

Male idiopathic hypogonadotropic hypogonadism is characterized by absent or partial sexual maturation. The Prok2/ProkR2 genes are among the genes implicated in this condition. Objective: Reporting a case harbouring a missense mutation in the PROK2 gene, presenting, at 7 1/2 years with micropenis and synkinesis. History and Examination: Born at full term, with no pre/post-natal complications. On presentation his penile stretched length was 3.8 cm, (-2.5 SDS). Both testes were descended, with a testicular volume of 2ml. Results: On follow up, the testicular volume of 4ml bilaterally, was detected at 11 1/2 years, after 3 testosterone monthly injections. The penile length increased to 5.2 cm. Puberty continued to progress spontaneously. Genetic Analysis revealed a heterozygous missense mutation in PROK2 gene, exon 4, chromosome 3. Conclusion: Heterozygous mutations in the PROK2 gene can present with reproductive and non-reproductive manifestations. They may progress spontaneously into puberty, in the absence of micro/cryptorchidism.