Table 2.

Genetic causes of puberty disorders

Category	Genetic causes
Precocious puberty
Central precocious puberty	Monogenic causes:
	(1) Gain-of-function (activating) mutations in KISS1R and KISS1 genes (kisspeptin pathway genes)
	(2) Loss-of-function (inactivating) mutations in MKRN3 gene
	(3) Loss-of-function (inactivating) mutations in DLK1 gene
	Chromosomal abnormalities:
	(1) 1p36 deletion
	(2) 9p distal deletion
	(3) 9q34.3 duplication (which includes the NOTCH gene)
	(4) Xp11.23-p11.22 duplication
Peripheral precocious puberty	(1) Testotoxicosis: constitutive activation germline mutations in the LHCGR gene
	(2) McCune Albright syndrome: postzygous somatic activating mutations in GNAS
Genetics of delayed puberty
Constitutional delay of growth and puberty	Genetic background is unknown. Probably pathogenic variants in the IGSF10 gene have been associated
Kallmann syndrome	Mutated genes: KAL1, FGFR1, FGF8, FGF17, IL17RD, DUSP6, SPRY4, FLRT3, KLB, HS6ST1, CHD7, WDR11, SEMA3A, SEMA3E, IGSF10, SMCHD1, CCDC141, FEZF1, SOX10, PROKR2, PROK2
Normosmic idiopathic hypogonadotropic hypogonadism	Mutated genes: CHD7, DAX1, FGF8, FGF17, FGFR1, HS6ST1, NSMF, LEP, LEPR, PROK2, PROKR2, WDR11, GNRH1, GNRHR, KISS1, KISS1R, SRA1, TAC3, TACR3
Hypogonadism hypergonadotropic	Monogenic causes:
	(1) Enzymatic defects in testosterone biosynthesis: 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase,
	17, 20-lyase and 17β-hydroxysteroid dehydrogenase deficiency
	(2) Inactivating mutations in the gonadotropin receptor genes
	(3) Polymalformative syndromes
	Chromosomal abnormalities:
	(1) Turner syndrome
	(2) Klinefelter syndrome