Background:
Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP).
Methods:
We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs.
Results:
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.
Conclusion:
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.