Constitutional delay of puberty is highly heritable, but its genetic basis is largely unknown. Rare genetic variants can cause congenital hypogonadotropic hypogonadism, but in approximately half of cases, no rare variant cause is found.
A study of nearly 350 individuals who consulted for lack of pubertal development within the framework of an International Consortium for the Study of Pubertal Delay, in which Drs. Grinspon and Rey from CEDIE participate, demonstrated that common genetic variants that influence the timing of puberty in the general population contribute strongly to the genetics of constitutional delay of puberty, weakly to normosmic congenital hypogonadotropic hypogonadism, and possibly do not contribute at all to hypogonadotropic hypogonadism with anosmia (Kallmann Syndrome). These findings demonstrate that the genetics of the common variants of constitutional delay of puberty and normosmic congenital hypogonadotropic hypogonadism are largely, although not completely, distinct.
Lippincott MF, Schafer EC, Hindman AA, He W, Brauner R, Delaney A, Grinspon R, Hall JE, Hirschhorn JN, McElreavey K, Palmert MR, Rey R, Seminara SB, Salem RM, Chan Y-M on behalf of the Delayed Puberty Genetics Consortium. Contributions of common genetic variants to constitutional delay of puberty and idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2025; 110(1):e61-e67. https://doi.org/10.1210/clinem/dgae166.
