Context: The focus of care in differences of sexual development (DSD) is mainly directed towards sex and gender development. Associated features are scarcely described. Widening the phenotypic spectrum of DSD might help to elucidate molecular aetiologies.
Objective: to determine the frequency of syndromic forms and to describe the associated features in 46,XY and 46,XX DSD patients.
Patients and methods: retrospective cohort study of patients with 46,XY and 46,XX DSD that have been admitted in the CHUV endocrinology and diabetology unit, the DSD multidisciplinary consultation or the paediatric urology unit and who were born before 01.01.2021.
Results: we included 79 patients (male: 64 /female 15). 69 had 46,XY and 10 had 46,XX karyotype. Diagnoses were as follow: CAH: n=10, AIS: n=9, gonadal dysgenesis: n=5 (partial: n=3 including 2 with residual Müllerian structures, complete: n=2), Anorectal malformation: n=2 (1 with residual Müllerian structures), 5alpha reductase deficiency: n=1, Denys-Drash syndrome: n=1, VACTERL: n=2, 46,XX DSD: n=1, 46,XY DSD: n=48 (including 5 with complex chromosomal rearrangement).
66 patients (83,6%) had an associated feature. Altogether, the five most associated features are as follow: facial morphology abnormalities (n=35), small for gestational age (n=30), orthopaedic abnormalities (n=23), nervous system morphology abnormalities (n=22) and cardiovascular system abnormalities (n=21). In the 46,XY subgroup, the most associated feature was facial morphology abnormalities (n=32). In the 46,XX subgroup it was adrenal glands morphology abnormalities (n=7).
Mean number of associated features per patient was 3,7 ± 3,2 [range:0-11].
Conclusions and perspectives: associated features are common in 46,XY and 46,XX DSD patients. This study emphasizes the need to investigate 46,XX and 46,XY DSD patients for associated features to allow early specific management of these patients and direct them toward novel genetic aetiologies.