Table 3.

Genetic Etiologies of Central and Peripheral Precocious Puberty

Abnormality	Mutation or Abnormality	Important Clinical Highlights
Central precocious puberty
• Monogenic causes	KISS1, KISS1R, MKRN3, DLK1	MKRN3 most common cause of familial CPP. KISS1, KISS1R, and DLK1 are very uncommon. DLK1 associated with metabolic syndrome phenotype.
• Syndromes
○ Temple	Maternal uniparental disomy or paternal deletion of chromosome 14q32.2	CPP in 90% of cases Loss of DLK1 expression
○ Russell-Silver	Hypomethylation of chromosome 11p15 or maternal uniparental disomy of chromosome 7	CPP in up to 25% of cases
○ Williams	Deletion of chromosome 7q11.23	CPP in 10–18% of cases
○ Prader-Willi	Paternal deletion or maternal uniparental disomy of chromosome 15q11-q13	CPP in 4–10% of cases
○ Neurofibromatosis type 1	NF1	Increased risk particularly in setting of optic pathway glioma
Peripheral precocious puberty
• Syndromes
○ McCune-Albright	Post-zygotic mutation in GNAS1	PPP most commonly presents in girls aged 1–5 years as sudden onset of painless vaginal bleeding
○ Familial male-limited	Activating mutation of LH precocious puberty receptor	Virilization in males prior to age 4. Enlarged phallus and pubic hair out of proportion to the small testicular volume.