Spectrum of Cytogenetic and Molecular Abnormalities in Disorders of Sex Development: A Retrospective Observational...

Disorders of sex development (DSD) are a social and medical emergency. A thorough history, detailed clinical examination, and appropriate investigations will help to identify the aetiology of DSD. But still, in most cases, the exact aetiology is not reached. Reaching a definite and firm diagnosis with the help of genetic testing is vital for the long-term management of DSD patients.

We conducted a hospital record-based, retrospective cross-sectional study of 20 children with DSD aged 0-14 years who attended the paediatric endocrine clinic at our institute from February 2022 to July 2024. Clinical, hormonal, radiological, cytogenetic, molecular and outcome data were analysed.

During the study period, 20 children were diagnosed with DSD at our institute. Their age range was between 0 and 14 years. Among them, 6/20 patients were diagnosed with 46, XX DSD, 12/20 with 46, XY DSD and 2/20 with sex chromosomal DSD. Cytogenetic analysis and whole-exome sequencing were done in all patients. Seven patients (35%) showed significant pathogenic variants in genes such as RSPO1, CYP21A2, CYP19A1, WT1, and SRD5A2. Out of seven genetically confirmed DSD patients, in only one was the gender of rearing changed after the diagnosis.

Management of DSD involves a multidisciplinary team from different specialities. The present study focuses on the cytogenetic and molecular diagnostic findings in children with atypical genitalia, which can be an efficient tool in the clinical diagnosis and management of DSD.