SNP Shot: Genomic Insights

Leydig cell hypoplasia is a disorder impacting male sexual development. Its key feature is the insufficient development (hypoplasia) of Leydig cells within the testicles. These cells are responsible for producing androgens, male sex hormones crucial for typical male sexual maturation both before birth and during adolescence.

In individuals with Leydig cell hypoplasia who possess a standard male chromosome configuration (46,XY), the condition can manifest in varying degrees of genital abnormalities. Affected males might exhibit a small penis (micropenis), hypospadias (where the urethral opening is located on the underside of the penis), or a bifid scrotum (a scrotum divided into two sections). These abnormalities can result in external genitalia that are not distinctly male or female, leading to ambiguous genitalia.

In more pronounced instances of Leydig cell hypoplasia, individuals with a typical male (46,XY) chromosome structure may present with female external genitalia. Their testes are typically small and undescended, meaning they are abnormally situated in the pelvis, abdomen, or groin area. These individuals fail to develop typical secondary male sexual characteristics, such as increased body hair, during puberty. Some researchers categorize this severe form as type 1 Leydig cell hypoplasia, while classifying less severe cases as type 2.

Inheritance:

The inheritance pattern for this condition is autosomal recessive. This indicates that both copies of the relevant gene in each cell must carry mutations for the disorder to manifest. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but generally do not display symptoms of the condition themselves. Leydig cell hypoplasia only appears in genetically male individuals (those with one X and one Y chromosome) who have mutations in both copies of the LHCGR gene. Genetically female individuals (with two X chromosomes) can inherit these mutations in both LHCGR gene copies, but because they lack Leydig cells, they do not develop Leydig cell hypoplasia. Instead, they exhibit normal female external genitalia and breast/pubic hair development, although they may experience delayed onset of menstruation (after age 16) and irregular menstrual cycles. In females, LHCGR gene mutations also inhibit ovulation, causing infertility.