Endocrine Abstracts

A regional multidisciplinary paediatric DSD clinic has been established in our university hospital since 2006, involving specialists from endocrinology and urology. Selected patients were referred to clinical genetics until 2015, when a clinical geneticist and genetic counsellor joined the DSD team. This was prompted by the increasing recognition of the role of genomics in DSD and availability of an increasingly diverse array of genomic tests through NHS labs. The clinic is held face-to-face 4 times a year, with two parallel rooms of one representative from each speciality (endocrinology, urology and genetics). We present an overview of the DSD clinic and the genomic landscape of DSDs from January 2015 to May 2024. 135 new patients were seen in the DSD clinic in this period. Congenital adrenal hyperplasia (CAH) was the commonest diagnosis, accounting for 23% (31/135) patients. One patient had 11-beta hydroxylase deficiency, and the rest had 21-hydroxylase deficiency. A wide range of DSD syndromes (total 35 patients, 26%) were diagnosed, including 7 patients with complete androgen insensitivity syndrome and 4 with 5-alpha reductase deficiency. Many patients with mosaic karyotypes involving the sex chromosomes were within this subgroup. Rarer DSD syndromes included Leydig cell hypoplasia, MAP3K1-related gonadal dysgenesis, and true isolated 17,20 lyase deficiency. The most diverse category (26/135, 19%) were patients with ‘other syndromes’, including monogenic, chromosomal and non-genetic diagnoses. In this category, 16 patients had a genetically confirmed diagnosis, from common syndromes (Prader-Willi, Noonan and Aarskog) to rare (Frasier syndrome) or super-rare (Lin-Gettig syndrome) disorders. One patient was diagnosed clinically with PAGOD syndrome, an extremely rare condition of unknown cause. 25 (19%) patients were diagnosed with an isolated urological anomaly such as hypospadias and/or undescended testes. 18 (13%) patients were found not to have a DSD after thorough assessment. Most referrals had been due to concern about appearance of the genitalia and family could be reassured. Our data highlights the crucial role of detailed phenotyping, family history, and genomic testing in increasing the diagnostic yield in patients referred to the DSD clinic, facilitating appropriate medical management, risk reduction (e.g. gonadoblastoma), and genetic counselling for the wider family.