Prenatal diagnosis of novel compound heterozygous variants in CYP11B1 causing 11β-hydroxylase deficiency in a fetus with unexplained agenesis of the corpus callosum: A case report

Rationale: Congenital adrenal hyperplasia is an autosomal recessive disorder caused mainly by deficiencies in 21-hydroxylase and 11β-hydroxylase (11-OHD). Pathogenic variations in CYP11B1 are mostly responsible for 11-OHD due to the deficiency of steroid 11β-hydroxylase. Patient concerns: The report describes a female fetus with 11-OHD that led to obvious virilization of the external genitalia, while unexplained agenesis of the corpus callosum was observed on fetal ultrasound and magnetic resonance imaging. Diagnoses: Amniocentesis was performed due to the advanced age of the mother. Multiple regions of homozygosity were detected on chromosomes 1, 2, 3, 8, and 9 of the fetus by chromosomal microarray analysis. Whole-exome sequencing was performed to exclude the possibility of autosomal recessive diseases. A compound heterozygous variant with two novel frameshifts of c. 61del (p.A21Hfs*30) and c.608_650del (p.A203Vfs*5) was detected on CYP11B1 (OMIM 610613) by genetic analysis. In addition, developmental abnormalities of the external genitalia were observed at 27 weeks of gestation, indicative of 11-OHD. Interventions: The parents decided to terminate the pregnancy after genetic counseling. Classic virilization of the external genitalia of the aborted fetus was observed. Outcomes: Sanger sequencing confirmed that the c. 61del variant was inherited from the father, whereas the c.608_650del variant was inherited from the mother. Both frameshift variants resulted in early termination of translation leading to a shortened peptide chain that affected the conformation and function of 11β-hydroxylase. Lessons: The report describes a female fetus with 11-OHD attributed to two novel deletions in CYP11B1 . These deletions resulted in a non-functional steroid 11β-hydroxylase protein and caused the obvious virilization of the external genitalia.