Discussion
Congenital adrenal hyperplasia (CAH) is a group of inherited disorders
that are present at birth where the adrenal glands are hyperplastic,
most commonly resulting from mutations or deletions of CYP21A. In CAH,
the body is missing an enzyme that stimulates the adrenal gland to
release cortisol. Disease severity and phenotypic presentation vary
depending on the location and extent of gene mutations or deletions,
which lead to complex allelic variations. Almost 300 CYP21A2 mutations
have been identified, making genotyping these individuals a cumbersome
undertaking. CAH can be seen as a continuum from salt wasting to mild
forms but is divided into two categories for convenience: classical
approximately 67% (“salt-losing,” severe, ex-congenital), and
nonclassical approximately 33% (“non-salt-losing” or
“simple-virilizing,” less severe, formerly known as late-onset or
cryptic) according to the degree of aldosterone deficiency Patients
with classic CAH may present as simple virilizing CAH or salt-wasting
CAH and are usually diagnosed in infancy while patients with
non-classical CAH may be asymptomatic or present with a milder form of
virilization postnatally. [5] CYP21, found on chromosome
6p, near the human leukocyte antigen gene cluster, is the gene for
adrenal 21-hydroxylase. Specific mutations may be linked to a degree of
enzymatic dysfunction and the clinical manifestation of 21-hydroxylase
insufficiency. Minor mutations on both alleles of the 21-hydroxylase
gene are found in patients with non-classic forms [6] A
retrospective cohort study conducted by Gidlöf et al. in Sweden found
the CYP21A2 genotype in 81% of the patients, reflecting improved
diagnostic usage of genetic studies. [7] The infant we are
reporting was diagnosed solely based on clinical findings and laboratory
values. Due to financial constraints and resource availability, genetic
studies could not be conducted in our case.
It is shown that up to 29.3% of CAH patients had adrenal tumors.
Abdominal ultrasound is the modality of choice for small-sized pediatric
patients due to the lack of ionizing radiation, lower cost than
cross-sectional imaging, and extensive availability. [8] In
our situation, the ultrasound of the infant resulted in the adrenal
glands being normal, ruling out the likelihood of an adrenal tumor.
Symptoms of Jacobs syndrome may be quite vague during childhood, and for
this reason, most children go undiagnosed. However, Men with Jacobs
syndrome who do display symptoms are most likely to exhibit tall stature
and macrocephaly. Developmental delays and behavioral issues have been
noted, as well as atonia, clinodactyly (medial curvature of a digit,
i.e., 5th finger toward the 4th), and hypertelorism. The incidence of
asthma and autism spectrum disorder also appears to be increased in
these individuals. [9] other conditions such as Marfan
syndrome and Sotos syndrome should be ruled out, in contrast to Jacobs
syndrome, Marfan syndrome often presents with cardiac abnormalities such
as aortic root dilatation and mitral valve prolapse. Sotos syndrome,
also known as cerebral gigantism, is a rare genetic condition caused by
a mutation in the NSD1 gene. Hallmark features include excessive growth
during childhood, macrocephaly, learning disabilities, hypotonia, and
seizure disorders. [10] Our patient had none of them.
Patients with Jacobs syndrome have been found to have an increased
incidence of certain diseases. These include asthma, seizure disorders,
and tremors. Some 47, XYY patients have been noted to have genitourinary
abnormalities such as microphallus, hypoplastic scrotum, cryptorchidism,
and hypospadias. These patients are also at an increased risk for
learning disabilities, ADHD, autism spectrum disorder, and speech
difficulties. [11]
The diagnosis of both CAH and Jacobs syndrome can be done prenatally
with amniocentesis or chorionic villus sampling, and treatment involves
dexamethasone administered at or before 10 weeks of gestation. A study
conducted by Carlson et al. found that prenatal diagnosis and therapy of
21-hydroxylase deficiency is safe and effective in lowering or
eliminating virilization in the affected female, sparing the newborn
female the repercussions of genital ambiguity, sex misassignment, and
gender confusion. [12] However, in our case, the mother did
not undergo routine antenatal visits during the pregnancy leading to the
failure of antenatal diagnosis of CAH as well as Jacob syndrome.
There is no treatment for XYY syndrome. The treatment option is
generally only supportive, with attention given to the comorbidities of
the patient. While medication cannot treat XYY syndrome, some
medications can be used to treat conditions related to the syndrome. A
person with XYY syndrome can get help with any learning or developmental
delays through speech therapy, occupational therapy, or other
assistance. Therapy can also help with ADD/ADHD, social interactions,
and other behavioral problems. While The treatment for CAH is based on
replacing normal glucocorticoid and mineralocorticoid needs, as well as
psychological support [13,14] The patient is currently
receiving hydrocortisone. The parents of the infant were counseled about
the need for genital surgery and psychological support.