Complex segregation analysis of hypospadias

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1000 male births. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Low birth weight is known to be an important risk factor for hypospadias, but several observations speak in favour of genetic factors as well. In order to delineate the relative contribution of the genetic factors behind hypospadias, we performed a complex segregation analysis of 2005 pedigrees in Sweden. The probands were ascertained through the departments of paediatric surgery and departments of plastic surgery and urology in Sweden where boys with hypospadias undergo surgery. In 7% of the ascertained families one or more additional cases of hypospadias were present. The complex segregation analysis showed a heritability of 0.99 and evidence for multifactorial inheritance. The results suggest that hypospadias might be due to monogenic effects in a small proportion of the families, but that there is a multifactorial cause for the majority of the cases.