Comments on some genetic abnormalities of sex determination and sex differentiation in Homo sapiens

Abstract

Man is a gonochoristic species with male hetero-and female homogamety. The basic plan of gonadal and genital development in both sexes is female unless testes are induced by H-Y antigen which is usually specified by the Y chromosome. Genitalia can develop in either direction in both sexes. In males testosterone produced by testicular Leydig cells causes Wolffian duct differentiation, and the anti-M~illerian hormone, produced by testicular Sertoli cells, causes Miillerian duct regression. Testosterone has to be converted to dihydrotestosterone by a 5a-reductase in endorgans to effect normal male external genital development. Individuals without gonads or with ovaries develop female genitalia--i.e, the female is the "uninduced" sex.Sex determination begins with parental meiosis and extends to the onset of normal gonadogenesis; sex differentiation includes all subsequent sex-developmental processes. Hermaphroditism, a rare condition, is a defect of the former process (gonadogenesis), pseudohermaphroditism, a relatively common condition of the latter (genital differentiation). Male sex development, being actively induced, is much more complicated than in females, and affords many more opportunities for mishap. Gonosomal aneuploidy 59601 rarely disturbs sex development; most intersexes have normal chromosomes. In order of frequency the most common disorders are: 1) hypospadias--technically a form of external male pseudohermaphroditism, but never referred to as such in clinical practice; 2) nonspecific, secondary male pseudohermaphroditism in isolated form or as component manifestation of many malformation syndromes; 3) the adrenogenital syndrome in females. Though less common than hypospadias, the adrenogenital syndrome must always be considered first in order to save life and to prevent recurrence. Genetic abnormalities of sex determination and sex differentiation in man are discussed together with experimental data elucidating the normal processes.

Hypospadias

“…The empiric recurrence risk was 12% (zero in coronal hypospadias, 14% in penile, and 18% in penoscrotal hypospadias. When a cousin or uncle was affected, in addition to the propositus, the recurrence risk was 19%, and when father and one son were affected the empiric *The above is reprinted from Opitz [1980], with permission of the editors and publisher.…”