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.