Complete androgen insensitivity syndrome caused by a novel mutation in the androgen receptor: A case report

Abstract

Introduction. Androgen receptor (AR) genes play an important role in human gonadal development. Complete androgen insensitivity syndrome (CAIS) is a disorder of sexual development caused by AR gene mutations. Children with CAIS have female external genitalia but a chromosomal karyotype of 46, XY and internal testes. Most children with CAIS are raised as females, and the current treatment is gonadectomy after puberty to ensure normal growth and development. Here, we identified a novel nonsense variant of the AR gene.The child's parents strongly requested immediate gonadectomy for the child due to psychological and oncological risks. CASE SUMMARYA female child, aged 1 year and 9 months, presented to the hospital with complaints of swelling in the groin on both sides for the last 9 months. Laparoscopic inguinal hernia repair was performed, and bilateral gonads with a testicular appearance and tubal umbrella structures were found without apparent uterine structures. Gonadal biopsy pathology indicated primitive testicular tissue, and the karyotype was 46, XY. Ultrasound showed testicular-like echoes near the internal inguinal ring on both sides but no detectable uterine or ovarian echoes. Gene sequencing revealed a c.2421C>A (p.Cys807Ter, 114) mutation in the AR gene, leading to a diagnosis of CAIS. Given parental concerns regarding psychological and oncological risks, bilateral gonadectomy was performed during the inguinal hernia repair operation.Conclusion. The discovery of this novel mutation enriches the spectrum of AR gene variants.When a female infant presents to the hospital with an inguinal hernia, clinicians should consider the possibility of CAIS. The guidelines on the timing of gonadectomy should be followed, but the psychological well-being of the child and the parents is a greater concern, and the final decision should be made in a holistic manner. Keywords. Complete androgen insensitivity syndrome; 46 XY disorders of sex development;Androgen receptor gene; Inguinal hernia; Gonadectomy;Core Tip: This study identified a novel mutation in the AR gene: c. 2421C>A (p.Cys807Ter, 114). The discovery of this novel mutation enriches the spectrum of AR gene variants. When a female infant presents to the hospital with an inguinal hernia, clinicians should consider the possibility of CAIS. The guidelines on the timing of gonadectomy should be followed, but the psychological well-being of the child and the parents is a greater concern, and the final decision should be made in a holistic manner.