ESPE Abstracts (2014) 82 P-D-3-2-967

ESPE2014 Poster Category 3 Sex Development (1) (11 abstracts)

Phenotypic and Genotypic Variability of Patients with 5-α Reductase Type 2 Deficiency

Kun Hu , Nils Krone & Jeremy Kirk

Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK

Background: Steroid 5-α reductase type 2 (SRD5A2) deficiency is an rare inherited disorder resulting from mutations in the SRD5A2 gene, causing 46,XY DSD (Disorder of Sex Development). The mutated SRD5A2 enzyme can no longer convert testosterone to dihydrotestosterone, which is needed for virilisation of external genitalia.

Objective and hypotheses: To describe the phenotype, investigations and management of SRD5A2 deficiency.

Method: Retrospective data was collected from the medical records of SRD5A2 deficiency patients seen at a regional paediatric endocrine centre over the last 20 years.

Results: Full medical records were available in eight patients. The median age of patients presenting at birth (n=5) and at puberty (n=3) were 1 year 1 month and 13 years 6 months respectively. Male patients (n=6) presenting at birth and puberty had symptoms including micropenis (n=6), hypospadias (n=5), undescended testes (n=4), penoscrotal transposition (n=2) and bifid scrotum (n=1). Female patients (n=2) who presented during puberty had symptoms including primary amenorrhea, absent breast development, palpable testes (n=1) and voice change (n=1). Pelvic ultrasound showed absent uterus and ovaries, and detectable testicular tissue. Rapid molecular genetic analysis confirmed homozygous recessive mutations in exon 4 of the SRD5A2 gene (c.598G>A; c.574G>A; c.586G>A) as well as compound heterozygous mutations in other exons of SRD5A2 gene (g.237_250dup and g.264C>G; c.586G>A and c.737G>A). After diagnosis, one of the female patients underwent a change in gender. Management included hypospadias repair, dihydrotesto-sterone 2.5% gel or orchidopexy.

Conclusion: SRD5A2 deficiency is a heterogeneous condition both in terms of age at diagnosis and presentation, and can be caused by several different mutations in the SRD5A2 gene. Better understanding of these phenotypic features can facilitate timely diagnosis, management and relevant counselling for patients and their families.

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