Hypospadias is a common congenital malformation in which the opening of the urethra (also called the meatus) is not in its regular location but at the underside of the penis.
Today, there are several known types of this disease in which hypospadias is a single finding, or as part of a set of symptoms or malformations of the reproductive system, or as part of a genetic disorder with other findings outside the reproductive system.
The prevalence of hypospadias as a single finding is 1-3 in 1,000 births, while the prevalence of other forms varies according to the different disorders.
In many cases of hypospadias, symptoms include a condition called chordee, which is a downwards curve of the penis. There is no uniformity regarding the severity of this disorder. In twenty percent of cases, the urethra opening is located at the base of the penis, while in sixty percent of cases it is located close to its natural location at the tip of the penis.
Other common accompanying malformations in the reproductive system include meatal stenosis (around eight percent of cases), an irregularly small penis and inguinal hernia (eight percent of cases), undescended testis (eight to fifteen percent of cases), other malformations of the upper urinary tract (two to twelve percent of cases), and more.
How is this condition inherited?
When hypospadias is an only symptom, inheritance is multifactorial. This means it is affected by various genetic and environmental factors. However, several cases have been documented in which this condition ran in families with an autosomal dominant inheritance pattern.
When hypospadias appears as part of a known syndrome, the inheritance pattern varies. Smith-Lemli-Opitz syndrome has an autosomal recessive inheritance pattern. Androgen insensitivity syndrome is inherited in an x-linked pattern.
Can the condition be diagnosed prenatally?
There is currently no diagnostic test that can detect the genetic mutation that causes hypospadias as a single symptom. It is possible to test the gene that causes Smith-Lemli-Opitz syndrome. This condition can be diagnosed in an antenatal ultrasound after low estriol in third trimester screening.
Women with a family history of Androgen insensitivity (at least one known case in the family can undergo screening for the relevant gene mutation. This is also possible after detecting other fetal abnormalities, such as a small penis.
Other related disorders
After a prenatal diagnosis of hypospadias, further testing is highly important to reduce the risk for multisystem disorders. Amniocentesis is recommended to rule out different chromosome abnormalities and to verify a male chromosome structure.
A thorough ultrasound scan is also highly important for ruling out other malformations, such as anus obstructions, hydrocephalus, heart defects, abdominal wall defects, and more. In addition, it is important to research family medical history for other cases of hypospadias.
In certain cases, a hormone test in the amniotic fluid or blood is also recommended to rule out male hormone abnormalities. In addition, other tests, such as steroid and cholesterol testing in the fetal blood, can help rule out Smith-Lemli-Opitz syndrome.
It is important to note that when no other irregular findings besides hypospadias are detected, there is a slightly higher risk for other congenital defects and intellectual disability (around three to four percent). Whenever these fetal abnormalities are detected, it is important to undergo comprehensive counseling in a multidisciplinary clinic to summarize all findings and discuss the parents’ options.