Genetic and other epidemiological risk factors of infants and children with hypospadias: a case control study

Abstract Background To study hypospadias as regard epidemiological risk factors and genetic association with mutations in Steroid 5 alpha reductase type 2 genes. Materials This study was conducted on two groups; the first group included 50 male children with hypospadias and the other group included 50 male healthy children as a matched control. All patients and controls were subjected to detailed history, physical examination and molecular study of 5-alpha-reductase gene polymorphisms (V89L and G34R). Results Mean age in hypospadias group was 3.28 ± 2.87 years. The most common type of hypospadias was the glanular type in 19 children (38%). Higher maternal and paternal age, consanguinity, rural residence and preterm labor carry significant epidemiological risk factors for hypospadias. According to genetic study, all healthy children carried the wild valine residue (VV) genotype, while only 44% of hypospadias cases carried the wild VV genotype and 56% carried the mutant L allele (homozygote for leucine residue and heterozygote for both valine and leucine (VL)) with high significant p value ( p < 0.001). For Allele Specific—polymerase chain reaction for glycine to arginine (G34R) mutation detection in the 5 alpha reductase type 2 gene, hypospadias children had significantly higher frequency of heterozygous GR genotype than healthy controls. Binary logistic regression analysis showed that mother age and rural residence were the most independent predictors for hypospadias. Conclusions V89L and G34R Steroid 5 alpha reductase type 2 gene polymorphisms, higher maternal and paternal age, consanguinity, rural residence and preterm labor carry significant risk factors for hypospadias. On multivariate logistic regression, mother age and rural residence are the most independent predictors for hypospadias.