Congenital adrenal hyperplasia with homozygous and heterozygous mutations: a rare family case report

Abstract

Background Congenital adrenal hyperplasia (CAH), characterized by defective adrenal steroidogenesis, is transmitted in an autosomal recessive manner. Mutations in the steroid 21-hydroxylase gene CYP21A2 causing steroid 21-hydroxylase deficiency account for most cases of CAH. The c.145l-1452delGGinsC gene mutation is rare, and only one case has been reported, but the form of gene mutation is different from this case, resulting in different clinical phenotype. The most common pathogenic genotype of CAH is a homozygous or compound heterozygous mutation, but CAH patients homozygous for the p.I173N mutation and heterozygous for the c.1451-1452delGGinsC mutation have not been reported previously. We report herein a familial case of CAH, in which both siblings carry the rare homozygous p.I173N mutation and heterozygous c.1451-1452delGGinsC mutation. Case presentation The proband showed amenorrhea, infertility, polycystic ovaries, and increased levels of androgen, rather than the typical clinical manifestations of CAH such as an adrenal crisis or masculine vulva, so was misdiagnosed with polycystic ovary syndrome for many years. Following a correct diagnosis of CAH, she was given glucocorticoid treatment, her menstruation became more regular, and she became pregnant and delivered a healthy baby girl. Conclusions The genotypes may be p.I173N homozygous or p.I173N/c.1451-1452delGGinsC heterozygous, both mutations could be pathogenic. This complex combination of mutations has not been reported or studied before. Through the report and analysis of this genotype, the content of CAH gene bank is enriched and the misdiagnosis rate of CAH is reduced.

Drug substitution and adjuvant therapy in patients with genetics related infertility: A review

“…CYP21A2 mutation, which results in steroid 21-hydroxylase production problems, is the main cause of congenital adrenal hyperplasia (CAH), a set of autosomal recessive genetic illnesses. Reduced corticosteroid 21-hydroxylase triggers compensatory increases in pituitary and hypothalamic corticotropinreleasing hormone release, which ultimately results in increased androgen and progesterone levels (41). The primary cause of the infertility problems experienced by 10%-30% of CAH women of reproductive age is testosterone excess-associated anovulatory cycles (42).…”

“…Retrospective studies revealed that glucocorticoids improved fertility by lowering ovulation dysfunction and preventing overexposure of the endometrium to progesterone and androgens from the adrenal glands. Patients with CAH who received glucocorticoids had more regular periods, became pregnant, and had healthy babies (41). Additionally, hormone therapy can be used throughout pregnancy with the main goals of restoring cortisol insufficiency, suppressing androgen overproduction, preventing the masculinization of female foetuses and preventing long-term consequences on child fertility (82).…”