ABSTRACT

Introduction:

Gain-of-function mutations in the KISS1 and KISS1R genes and paternally inherited loss-of-function mutations in the Delta-like noncanonical Notch ligand 1 (DLK1) and imprinted Makorin ring finger protein 3 (MKRN3) genes are the most common genetic causes of familial central precocious puberty (CPP) cases. This report presents a girl with a family history of early puberty and a pathogenic variant in the MKRN3 gene.

Case Report:

The girl who was seven years and four months old with breast and pubic hair development was referred to pediatric endocrinology clinic. Medical history was usual and her parents were unrelated. Her father, paternal uncle, and cousins had a history of CPP. At the time of the first visit; weight was 34 kg (2.06 SD), height 127 cm (0.78 SD), BMI was 1.95 SDS, with a target height of 148.1 cm (-2.01 SD, mother height -1.52 SD, father height -3.44 SD), breast Tanner stage III, pubic hair Tanner stage II. In laboratory examinations, basal LH and estradiol tests were high, thyroid function tests, and routine biochemical studies were normal. Bone age, according to Greulich-Pyle was 10.5 years. On pelvic ultrasound, the long axis of the uterus was increased. LH-RH stimulation test was indicative of CPP. Considering the family medical history of the father’s side, we suspected a genetic cause for the CPP and MKRN3 gene. MKRN3 gene analysis showed a previously identified c.482dupC heterozygous variant in the patient and her father. Treatment with Gonadotropin-releasing hormone analog was continued until the bone age reached 12.5 years. Our patient is now 12.5 years old and has regular menstruation, and with the help of the treatment, her height has exceeded the target height.

Conclusion:

In evaluating CPP cases, family history and genetic analysis are important in terms of early diagnosis and treatment with genetic counseling of the next generations.

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MKRN3 Gene Mutation in a Case of Familial Central Precocious Puberty

ABSTRACT

References