Is Hypospadias a Genetic Problem? 

I saw a charming young couple in my clinic today. They brought their 1-year-old son to me for hypospadias surgery. After examining the child, I discussed the plan of treatment with them. They were obviously concerned that their child has this defect of his penis and would require surgery at such a young age! Further, they had apparently read somewhere that hypospadias is a genetic problem. Just before they left my clinic, they asked a common question asked by parents of a child with hypospadias “Doctor, if we have another child (boy) in future, is he also going to get hypospadias?” 

The answer to this question is “not necessarily”; that means if one child in the family has hypospadias, it is not a rule that the next male child also will have hypospadias. I’ll explain with some simple examples:  

1. We operate on thousands of hypospadias children, but we have seen only a few families who had more than one child with hypospadias 

2. We have seen several pairs of ‘identical’ twins; one of them had hypospadias, while the other did not. Identical twins are the best examples of both siblings sharing common genetic material. If hypospadias was a purely genetic defect, we would have expected both twins to have the defect. 

3. We have seen families where even among triplets, only one child had hypospadias, and the other two boys were normal. 

4. Several genetic studies have been done in hypospadias patients, but no specific gene causing the defect has been identified yet 

5. Hypospadias is probably caused by a yet unknown list of environmental factors. These could be chemicals called endocrine disruptors, plastic and industrial wastes and so on. 

Only a small proportion of hypospadias, typically the severe variety with associated abnormalities of the testis or a micropenis (very small penis), may have a genetic basis. Thus, most (95%) hypospadias cases are not genetic problems but are caused due to some disruption in the normal penile development in the womb. A timely and good operation cures most of these children, and they do well without major problems in future.  

In those children where a genetic defect is suspected as the cause of hypospadias, hormonal and genetic studies need to be done. On the basis of these results, it is possible to identify specific genetic defects in most cases. This helps in 2 ways: to treat the child with appropriate hormones as necessary; second, to identify any specific genes that might cause an increased risk of genital abnormalities in the future offspring of that family.  

One of the common defects causing severe hypospadias is the 5-alpha reductase enzyme deficiency. This enzyme converts Testosterone (T) into its active form Dihydrotestosterone (DHT). If this enzyme is deficient, the development of external genitalia is affected, manifesting as severe hypospadias with a small penis (micropenis). The testes are usually normal in these children. The correct diagnosis of this condition involves both hormonal and genetic testing. Treatment with testosterone in these children may not help to increase the size of the penis; unless the penis has a reasonable size, hypospadias repair cannot (should not) be performed. Thus, it is important to diagnose this condition correctly and treat the child with DHT cream application to increase the size of the penis and make them fit for hypospadias repair. Once properly treated with appropriate medication, satisfactory results of hypospadias repair can be obtained in these children in expert hands.   

Thus, it is important for the parents of a hypospadias child to consult the correct specialist, who has enough experience to suspect such problems so that they can be diagnosed and properly treated. Otherwise, surgery on these children without proper diagnosis typically has high failure rates, which is difficult even for the expert surgeon to correct later.