Leydig cell agenesis

Leydig cell hypoplasia is an autosomal recessive disorder in which loss of function of the LHCGR gene in the male prevents normal sexual development. Two types of LCH have been defined (Toledo, 1992). Type I, a severe form caused by complete inactivation of LHCGR, is characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high LH levels, total lack of responsiveness to LH/CG challenge, lack of breast development, and absent development of secondary male sex characteristics. Type II, a milder form caused by partial inactivation of the gene, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias. Females with inactivating mutations in the LHCGR gene display a mild phenotype characterized by defective follicular development and ovulation, amenorrhea, and infertility (review by Themmen and Huhtaniemi, 2000). Reviews Arnhold et al. (2009) noted that the clinical manifestations of female patients with hypogonadotropic hypogonadism due to isolated LH deficiency (HH23; 228300) are very similar to those of women with hypergonadotropic hypogonadism due to inactivating mutations of the LH receptor: all have female external genitalia, spontaneous development of normal pubic hair and breasts at puberty, and normal to late menarche followed by oligoamenorrhea and infertility. Pelvic ultrasound shows a small or normal uterus and normal or enlarged ovaries with cysts. However, women with LHB (152780) mutations can be treated with luteinizing hormone or chorionic gonadotropin (CG; 118860) replacement therapy; women with LH receptor mutations are resistant to LH, and no treatment is effective in recovering their fertility. [from OMIM]