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This is a common anomaly of the penis manifesting as an opening on the lower aspect instead of at its end.

It is important to differentiate between several types:
  • The isolated (non-syndromic) type, in which hypospadias is the sole finding.

  • Hypospadias as part of a general syndrome:

    1. Syndromes involving other defects of varying degrees of severity in the reproductive system. These usually arise from disorders in hormone secretion or hormone receptors in the genitalia.

    2. General genetic syndromes involving other organs or systems apart from the reproductive system.

In many cases hypospadias is associated with a downward bending of the penis, a condition called chordee. This can be of varying degrees of severity. In the severe cases (20%) the opening is at the lower end, i.e. at the base of the penis close to where it arises from the body. In the milder cases (60%), the opening is close to its normal site.

Some of the cases are accompanied by other defects, such as a narrowing of the urethral opening (8%), micropenis, inguinal (groin) hernia (8%), or cryptorchidism, where the testes are in the abdomen (8 - 15%). Sometimes there are also upper urinary tract defects (2 - 12%). These defects are not usually severe and can be detected by ultrasound.

It is important to carry out chromosome analysis in order to confirm that this is normal male, 46,XY. The finding of other defects or abnormalities is also important. Ultrasound examination in pregnancy cannot be used to ensure that the internal reproductive organs are normal, for example to detect whether a uterus is present, or ovaries or testes, etc. It is important to look for abnormalities in the descent of the testes and to ascertain whether the testes themselves are normal. It is also important to know whether there are other cases in the family, which helps to differentiate between the different types, as detailed below.

Clinical signs

Isolated (non-syndromic) hypospadias

This has a frequency of about 1 - 3 in every thousand newborns.

In most of the cases (approximately 90%) hypospadias with or without chordee is the only abnormality and the children do not have any other problems.

The hypospadias can be surgically repaired, preferably at the age of about a year and a half, especially if the opening is far from the usual site and the chordee is severe, leaving the foreskin in order to allow greater operative success.

There may be a hernia or cryptorchidism associated with the hypospadias, which nevertheless is still the isolated non-syndromic type.

This type of hypospadias may be transmitted by autosomal dominant inheritance. If there are other cases in the families of either or both parents, for example the father, this supports hereditary transmission. Sometimes it becomes apparent that there are other family members with this condition only after a thorough examination, as some cases are very mild and are not noticed by other relatives. If this condition is found in the father or in other relatives, it is important to examine them to ensure that the hypospadias is the isolated (non-syndromic) type with no other associated defects.

The syndromic form: hypospadias as part of a general syndrome.

  • Syndromes involving other defects of varying degrees of severity in the reproductive system:

    An example of a mild condition is a syndrome where hypospadias is associated with cryptorchidism, where the testes have not descended into the scrotum and remain in the abdomen or in the inguinal canal leading to the scrotum. A more severe and less common type is incomplete male development due to hermaphroditism, a condition where there are present elements of both male and female reproductive organs. This usually results from abnormalities in the secretion of various hormones or defects of the hormone receptors in the reproductive organs, such as a deficiency in certain enzymes in the adrenal gland, which interferes with the normal secretion of male hormones. Examples are a deficiency in the enzyme desmolase or other enzymes in the body's steroid cycle. Another example is a lack of, or reduction in the level of, the receptor for the main male hormone, a condition called androgen insensitivity. Because of this the male hormones do not function, resulting in a lack of development of normal male external sexual characteristics of varying degrees of severity, up to a completely female appearance, in which case there is no hypospadias, as the external genitalia are female.

  • Syndromes also involving other organs apart from the reproductive system:

    Here the hypospadias is mainly associated with defects such as heart defects, deafness, congenital anal atresia, hydrocephalus (dilation of the ventricles of the brain), defects in the closure of the abdomen, and defects in the neuromuscular system. Some of the classic syndromes are: various chromosomal syndromes, Smith Lemli Opitz syndrome.

Inheritance pattern

The isolated (non-syndromic) type

Hereditary transmission here is most probably multifactorial, i.e. a number of genes act together, possibly in association with environmental effects. In some families in which some family members have non-syndromic hypospadias, hereditary transmission is autosomal dominant limited to males only.

The syndromic type

Here the type of inheritance depends on which syndrome the patient has. Some cases, mainly those associated with hormonal deficiencies or a defect in the hormone receptors in the reproductive organs, such as Smith Lemli Opitz syndrome, are transmitted by autosomal recessive inheritance. In other cases, mainly androgen insensitivity, the inheritance is X-linked.


In the isolated type, this is incomplete. This means that there may be instances where some members of a family that has several individuals with hypospadias may be born without hypospadias, but their children will be affected. These family members carry the gene for hypospadias but do not express it.

Associated features that can be demonstrated in tests performed during pregnancy

If hypospadias is detected in pregnancy, it is very important to perform additional tests in order to look for a multisystem syndrome.
  • Amniocentesis should be considered in order to look for a chromosome disorder and to determine the karyotype (chromosome arrangement) - if this is 46,XY it is normal male.

  • It is necessary to perform a comprehensive and thorough ultrasound scan. The purpose of this examination is to look for defects such as micropenis and also defects in the upper urinary tract (2% - 12%). It is important to look for other defects as well, especially heart defects, deafness, anal atresia, hydrocephalus (dilated brain ventricles), defects in the closure of the abdominal wall, and neuromuscular defects. Ultrasound examination in pregnancy cannot be used to ensure that the internal reproductive organs are normal, for example to detect whether a uterus is present, or ovaries or testes, etc. It is important to look for abnormalities in the descent of the testes and to ascertain whether the testes themselves are normal. It is important to know, of course, whether there are other cases in the family. Other affected individuals should be referred to an endocrinologist and geneticist for examination and to undergo laboratory tests if necessary. In this way, different types may be differentiated.

  • Sometimes it is necessary to perform hormone tests on the amniotic fluid or blood in order to rule out a disorder of the male hormones, and/or special tests such as cholesterol and steroid levels in amniotic fluid or blood in order to test for Smith Lemli Opitz syndrome.

If the hypospadias is the only abnormality and the results of these tests are normal, this indicates a significantly decreased risk for a genetic syndrome. However, there is still a small extra risk of approximately 2%, although there are no precise, reliable figures, in excess of the normal risk in the general population for defects and mental retardation, which is 2% - 4% when all the test results are normal. As mentioned, there may be syndromes that are not detected by the tests that can be performed during pregnancy without additional signs, such as G syndrome etc., but these are not very likely.

In all these cases it is important to refer the couple for genetic counseling, to which they should bring all available data, including the results of other tests performed during the pregnancy such as alpha-fetoprotein, nuchal translucency, etc.

It is advisable to refer the parents to a multidisciplinary clinic in a hospital for professional counseling by a geneticist, an expert in ultrasound examinations, a pediatric endocrinologist, a plastic surgeon or urologist, and a neonatologist, in order to collate all the data and discuss the various possibilities and courses of treatment that are available, etc. The decisions taken will depend on the severity of the problem, the presence of additional findings, etc.

What is the risk of recurrence in a subsequent pregnancy?

Isolated (non-syndromic) hypospadias

In cases where the affected individual is the only one in the family:
If this is the first case in the family, and it is the isolated (non-syndromic) type of hypospadias, the risk of recurrence in another child is approximately 15%. A father with hypospadias has an increased risk of fathering a child with the same condition. 8% of men with hypospadias have an affected child or affected children. The risk for more distant relatives depends on the number of affected individuals in the family, the relationship to the affected individuals, etc. This risk is ascertained within genetic counseling.

If there are many affected individuals in the family:
In a small percentage of families there may be hereditary transmission of a specific abnormal gene that can be identified. It is important to examine these cases thoroughly and to check for such a specific gene that is transmitted by autosomal dominant or X-linked inheritance, and whether it may also be involved in defects other than hypospadias. As the gene for these defects is not always expressed, especially in the mother, each of the parents can carry it without actually being affected. In such a case there is a risk of recurrence in subsequent pregnancies. Recurrence can also occur in more distant relatives carrying the same abnormal gene.

In cases of syndromic hypospadias, the exact risk of recurrence must be evaluated. This varies according to which syndrome the patient has. In some cases the syndrome is sporadic, either as a result of a new mutation or a chromosome disorder, and in other cases there is a hereditary syndrome such as Smith Lemli Opitz syndrome, an autosomal recessive disease with a recurrence risk of 25%, or an X-linked syndrome such as androgen insensitivity syndrome.

Genetic molecular information

The gene for the disease

No gene exclusively responsible for isolated hypospadias has been found. Conversely, genes for syndromes in which hypospadias is a part have been found, particularly the genes for Smith Lemli Opitz syndrome and androgen insensitivity syndrome.


The gene for androgen insensitivity syndrome is located on the X chromosome.

Genetic testing

Diagnostic testing

There is currently no simple genetic test for diagnosing the defect associated with isolated (non-syndromic) hypospadias. In very large families, it is possible to perform linkage analysis tests (see: Indirect testing for genetic markers in a family that has one or several patients - when there are a number of different genes that can each cause the disease - the gene, or most of the genes not having been located / identified / mapped - multifactorial diseases).

  • It is possible to test for the Smith Lemli Opitz gene, but this is not usually necessary, because there is a biochemical test that can be used to diagnose patients, including fetuses, where the amniotic fluid can be examined.

  • It is possible to test for the gene for androgen insensitivity syndrome located on the X chromosome, and it is worth doing this in families in whom there is apparent X-linked inheritance of hypospadias with or without other defects in the urinary tract.

Carrier testing

For the isolated type - as for diagnostic testing. For syndromes of which hypospadias is a part - if the mutation has been found in the gene responsible for hypospadias in the family, carriers can be identified - see for each disease individually.

Fetal testing

When hypospadias is detected in pregnancy and there are no other known cases in the family, it cannot be proved that this is isolated hypospadias. Some differential diagnoses can be ruled out mainly by the tests listed above.

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