Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population

Objective: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development.The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population.Design: Case series.Setting: Five public hospitals in Hong Kong.Patients: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011.Main outcome measures: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling.Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification.Results: Overall, 64 patients were recruited for the study.Their age at presentation ranged from birth to 17 years.The majority presented with ambiguous external genitalia including micropenis and severe hypospadias.A few presented with delayed puberty and primary amenorrhoea.Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations.Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. Conclusions: Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population New knowledge added by this study • The most common likely causes of 46,XY disorders of sex development (DSD) in our local Chinese population are 5α-reductase 2 deficiency and androgen insensitivity syndrome.• Blood hormone testing is unreliable in differentiating between androgen insensitivity syndrome and other causes of 46,XY DSD.• Mutational analysis of the SRD5A2 and AR genes should be considered the first-line investigation in patients with 46,XY DSD.Implications for clinical practice or policy • When encountering patients with 46,XY DSD, 5α-reductase 2 deficiency and androgen insensitivity syndrome should be considered early as their presence has implications for treatment and prognosis.