Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case

Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP).

We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs.

The girl was screened at the age of 4 years because of a positive family history; her sister had developed CPP at 6 years of age and was found to harbor the MKRN3 p.Pro161Argfs*16 mutation, inherited from their asymptomatic father. During close follow-up, she initially developed increased growth velocity at 6 years (9 cm/year), followed by a slightly increased basal luteinizing hormone level (0.4 mIU/ml) and, ultimately, clinical thelarche with rapid progression (Tanner stage 1-3) between 6.3 and 6.7 years. In the context of a loss-of-function MKRN3 mutation and a positive family history, these features established the diagnosis of CPP and supported the initiation of treatment with a gonadotropin-releasing hormone analog. The absence of significant bone age advancement, pubic or axillary hair, or behavioral or social problems could be ascribed to the early diagnosis.

The identification of carriers of MKRN3 mutations may contribute to early diagnosis of CPP, facilitating treatment decisions and guiding genetic counseling and prompt intervention in familial cases.