46XY Disorder of Sexual Differentiation in Five Generations: A Preliminary Report

This is a preliminary report of 21 members of an extended family having 46XY DSD in 5 generations. The salient features of the affected members and the mode of transmission is highlighted. It is observed that the disorder is transmitted by only male members of the family, all normal females through five generations have always given birth to normal offsprings, who in turn have produced normal children. All affected members have karyotype of 46XY. There is a wide variation in the phenotype of the affected individuals, ranging from a normal female to an ambiguous male. All the individuals reared as males and whom the author examined had unilateral or bilateral undescended testes, perineal hypospadias and a vagina. All had varying extent of Mullerian elements in their pelvis. Two of the individuals reared as females also had menstrual periods and were married, but had to undergo gonadectomy due to malignancy of the gonads. The incidence of gonadal malignancy was found to be 30% in one cohort. This is the first time that such a large number of 46XY DSD in a single family is being reported. Genetic studies of the normal and affected members of the family are not yet done, but will be undertaken in order to determine the nature of the underlying gene and its location.