Introduction
Congenital adrenal hyperplasia (CAH) describes a family of autosomal recessive diseases caused by gene mutations encoding enzymes in the cortisol biosynthesis pathway. The clinical and biochemical manifestations of CAH are quite variable. The most common form of CAH, making up more than 95% of congenital adrenal hyperplasia cases, results from 21-hydroxylase deficiency (21OHD), due to loss of function mutation in CYP21A2. Classic CAH from 21OHD occurs in 1:10,000 to 1:20,000 live births with a female/male ratio of 2:1. [1]Disease severity and phenotypic presentation vary depending on the location and extent of gene mutations or deletions, which lead to complex allelic variations.
Jacobs syndrome also known as 47, XYY syndrome, is caused by the insertion of a male Y chromosome to 46, XY. It occurs in 0.1 % of the male population. Additionally, there are no specific clinical manifestations in most boys with the XYY karyotype. Diagnosis of an XYY karyotype is delayed (mean age at diagnosis is 17.1 years) and only 15% of patients are diagnosed with XYY syndrome. The karyotype 47, XYY is relatively common, but its phenotypes are not well-understood. Patients may vary greatly, ranging from no phenotype and relatively few abnormalities to multi-systemic symptoms; for a specific symptom, the severity can vary among individuals. [2]
XYY has also been sporadically reported in connection with several cases of disorder of sex development (DSD). Ambiguous genitalia is the condition commonly found in disorders of sex development (DSDs) characterized by imperfect differentiation of external genitalia between males and females. Sex Chromosome mosaicisms like 45 X0/46, XY, or 45 X/47 XYY have been considered major causes of ambiguous genitalia. Such DSD phenotypes of XYY patients include micropenis, testicular dysplasia, true-hermaphrodite, and complete sex reversal.[3] Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common cause of ambiguous genitalia in genotypically normal female infants (46XX). Most males have no signs of CAH at birth. However, some may present with hyperpigmentation and penile enlargement while those with salt-wasting disease present early with hyponatremia and hypovolemia. Males with non-salt-wasting disease present later with signs of virilization. In rare forms, males are under-masculinized.[4] This report highlights the rare case of congenital adrenal hyperplasia coexisting with Jacobs syndrome presenting as ambiguous genitalia.
Case presentation: A 5-month-old infant was brought to the outpatient department of a tertiary care hospital for ambiguous genitalia. The infant was born at 36 weeks of gestation to a 26-year-old primigravida mother. The marriage was non-consanguineous and the paternal and maternal ages were 30 and 26 years respectively. The pregnancy was complicated due to delayed fertility for three years and the mother revealed the use of herbal medicines during this period. The infant had a birth weight of 3kg with an APGAR score of 9 at both 1 and 5 minutes.