Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Aim: we report a case of a patient with pseudovaginal perineoscrotal hypospadias presenting with gender dysphoria in adulthood after being raised female, with the diagnosis of 5α-reductase deficiency confirmed following molecular genetic sequencing. This highlights the potential benefits of genetic testing over routine hormonal screening for this disorder which are often inaccurate. 

Methods: case report of a man presenting with pseudovaginal perineoscrotal hypospadias who underwent hormonal, karyotyping and molecular genetic investigations. His background was complicated by a previous orchidectomy in infancy. We subsequently performed a literature review focusing upon the epidemiology and previous clinical presentations of 5α-reductase deficiency, it's known molecular variant associations (ie. mutations in SRD5A2 gene)[1] and rates of comorbid gender dysphoria[2]. 

Results: karyotyping was performed which confirmed a 46 XY karyotype on cytogenetic analysis. There was presence of SRY mutation on quantitative fluorescent polymerase chain reaction. Biochemistry results are included below, pre- and post testosterone replacement after 44 weeks (Table 1). 

Whole exome gene sequencing was performed which demonstrated pathogenic compound heterozygous variants in the SRD5A2 gene (c.383_384delinsGA and c.607G>A).

Conclusion: 5α-reductase deficiency is an exceedingly rare cause of disorder of sex development in males which typically presents with ambiguous genitalia at birth[3]. It is phenotypically broad and may mimic more common conditions such as androgen insensitivity syndrome at birth[4]. Molecular genetic testing offers an alternative accurate diagnostic test to routine hormonal investigations and this earlier diagnosis may help limit the medical and psychosexual complications which are common in patients with disorders of sexual development.