Hypogonadism, Male

Description

Familial male hypogonadism is a highly heterogeneous category from which some disorders such as Reifenstein syndrome (312300), Kallmann syndrome (see 308700), isolated gonadotropin deficiency, and some other entities can be separated. The presence of an autosomal recessive form is suggested by the occurrence of parental consanguinity (Nowakowski and Lenz, 1961).

Clinical Features

Ferriman (1954) described a possibly distinct form in 2 sons of first-cousin parents. First-degree hypospadias, small penis, gynecomastia, markedly diminished secondary sexual characteristics, and normal-sized testes were described. In all respects except the parental consanguinity suggesting recessive inheritance, the disorder clinically resembled Reifenstein syndrome (312300).

Cytogenetics

In a Caucasian male with hypogonadism and testicular atrophy, Quintero-Rivera et al. (2007) identified an apparently balanced translocation t(8;10)(p11.2;p13), which was also found in his mother and maternal grandmother. There were no known genes disrupted by the 8p11 breakpoint; however, FISH mapping with overlapping BAC clones of the 10p13 breakpoint demonstrated disruption of the NMT2 gene (603801) between exons 1 and 3. The authors suggested that dysfunctional N-myristolylation is a possible mechanism for testicular failure, either directly or in concert with viral insults.