Genetic aspects of hypospadias

Abstract

After tabulating the occurrence of hypospadias among other family members, it was determined that 21% of the 307 families studied had a second family member with this anomaly. 15 families (5%) had 3 affected members. 14% of all brothers of the proband had a similar abnormality. 7% of fathers of the index child were affected, while 2.5% of the male cousins and 1.8% of uncles of the proband had hypospadias. Thus, every family member category showed an increased risk for the occurrence of hypospadias when compared with the potential risk for the general male population. The question was asked 'What is the risk of a second boy being born with hypospadias when this anomaly appeared for the first time in the proband?' There were 265 such families. 197 additional male children were born to this subgroup, and 23 were affected. This establishes the risk factor for the second male sibling at 12%. No child with coronal hypospadias had a brother with hypospadias. When the proband had penile or penoscrotal hypospadias, a 14 and 18% chance existed, respectively, for an additional male sibling to be born with hypospadias. Thus, we have found the potential risk to increase with the severity of the disease in the index child. The risk of a second boy being affected was determined when hypospadias was already present in another family member (uncle or male cousin) in addition to the index child. 23 families had 2 such members (families in which the father was the second affected member were excluded). In this subgroup, 18 brothers were sired and the anomaly occurred in 3 of these siblings. The risk factor in this family situation was 19%. When this anomaly was present in the index child and his father (19 families), the risk of a second sibling being born with hypospadias approached 26%. Thus, the chance of a second son being born with hypospadias increased when the anomaly was already present within a family, especially if it occurred in a first degree relative.