Fetal abnormalities » Genital tract
- 1 in 5,000 births.
- Female fetus: clitoromegaly with normal labia.
- Male fetus: micropenis, hypospadias, undescended testes, bifid scrotum.
- On the basis of the cause, the condition is divided into:
- True hermaphrodite: both ovarian and testicular tissue are found within the same gonad. The karyotype is female 46,XX, but there is a chromatinic material from the Y chromosome.
- Female pseudohermaphrodite: virilized females with normal female karyotype and ovarian gonadal tissue. The causes include congenital adrenal hyperplasia (1 in 15,000), ingestion of androgens by the mother and maternal virilizing tumors.
- Male pseudohermaphrodite: undervirilized males with normal male karyotype and testicular tissue. The causes include inadequate synthesis of testosterone or the presence of an androgen receptor defect.
- Chromosomal abnormalities, mainly trisomy 13, triploidy and 13q syndrome, are found in a few cases.
- The condition is commonly associated with genetic syndromes:
- Smith-Lemli-Opitz syndrome: autosomal recessive; ambiguous genitalia, microcephaly, cardiac, renal and gastrointestinal defects, syndactyly and polydactyly.
- WAGR syndrome: sporadic; Wilms tumor, aniridia (absence of the iris), geniturinary malformations, neurodevelopmental delay.
- Other defects, mainly facial clefts and cardiac defects are often found.
- Detailed ultrasound examination.
- Look for maternal signs of hyperandrogenism (acne, deep voice, development of hirsuitism during pregnancy) and enquire about ingestion of androgens during the first trimester and family history of ambiquous genitalia.
- Determine genetic sex by invasive testing or cfDNA in maternal blood.
- Families at risk of congenital adrenal hyperplasia: invasive testing for DNA analysis.
- Cases suspected of Smith–Lemli–Opitz syndrome: amniocentesis and measurement of 7-dehydrocholesterol; high levels suggest the diagnosis.
- In families with congenital adrenal hyperplasia, administering dexamethasome to the pregnant woman from 6 weeks’ gestation can minimize the effect of androgens on the genitalia and the developing brain. If the fetus is male, steroids should be discontinued.
- Follow-up scans every 4 weeks to monitor growth and evolution of genitalia.
- Standard obstetric care but delivery should be in a tertiary center.
- Treatment of a neonate with ambiguous genitalia should be performed by a multidisciplinary team, including geneticists, pediatric endocrinologists, and pediatric urologist. There is controversy concerning sex assignment and the need or not of reconstructive surgery.
- Congenital adrenal hyperplasia: 25%.