Novel mutations of the CYP17A1 gene cause disorders of sex development in two-chromosome karyotype 46,XY infants and a literature review: A case report

Abstract

Background Congenital adrenal hyperplasia is a group of rare autosomal recessive diseases due to seven different enzyme mutations, and 17ɑ-hydroxylase deficiency is rare in congenital adrenal hyperplasia. The typical clinical manifestations of 17α-OHD are sexual naivety, with vague or feminine apparent definition of the external genitalia; pubescent and adult females present with no pubertal development and primary amenorrhea, and males show vulval dysplasia or femininity. Case presentation: The clinical features and laboratory and whole-exon sequencing test results were analysed in the 2 children with the chromosomal karyotype 46,XY 17ɑ-OHD at the ages of 2 months and 20 days (case 1) and 1 year and 2 months (case 2). Case 1 presented with cryptorchidism and a small penis with an external masculinization score of 7. Case 2 showed feminine external genitalia with a score of 4. Decreased morning cortisol levels, normal electrolytes and significantly increased luteinizing hormone and follicle-stimulating hormone were present in both cases. Both patients harboured compound heterozygous mutations in the CYP17A1 gene, and among them, had three novel mutations. Conclusions CYP17A1 gene defects in infants can manifest only as gonadal dysplasia and a lack of blood pressure and electrolyte abnormalities, which are easily misdiagnosed. Those with internal and/or external genitalia inconsistent with the chromosome karyotype should be alert to the possibility of 17ɑ-OHD. Adrenal steroid hormones and gene testing can be helpful for a definite diagnosis and early intervention.