Variable presentation of precocious puberty associated with the D564G mutation of the LHCGR gene in children with testotoxicosis.

We report on a family with familial male-limited precocious puberty (FMPP) due to a D564G mutation of the LHCGR gene. Family members show a varied phenotypic expression from severe precocity unresponsive to therapy with compromise of the predicted final height in some members, to attainment of tall final stature in other members who never received medical treatment. DNA amplification and sequencing of exon 11 of the LHCGR gene was done for the three affected male members and their mother. DNA analysis revealed a D564G mutation in the third cytoplasmic loop of the LHCGR receptor. All three males had precocious puberty with elevated testosterone levels. The index case developed central precocious puberty and evidence of compromised final height while on therapy. In contrast, the untreated older siblings attained a tall final height. This report underscores the possibility that the effects of the mutant luteinizing hormone/choriogonadotropin receptor on phenotypic expression of FMPP, such as adult final height, are modified by other factors.