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

Hong Kong Med J. 2015 Dec;21(6):499-510. doi: 10.12809/hkmj144402. Epub 2015 Oct 16.


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.

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 amenorrhea. 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 are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

Keywords: Disorders of sex development; Female; Male; Mutation/genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / deficiency
  • 46, XX Disorders of Sex Development / etiology
  • Adolescent
  • Amenorrhea / etiology
  • Androgen-Insensitivity Syndrome / etiology
  • Asian People*
  • Child
  • Child, Preschool
  • Cholesterol Side-Chain Cleavage Enzyme / deficiency
  • Congenital Abnormalities / etiology
  • DNA Mutational Analysis
  • Dihydrotestosterone / blood
  • Disorder of Sex Development, 46,XY / blood
  • Disorder of Sex Development, 46,XY / etiology*
  • Disorder of Sex Development, 46,XY / urine
  • Female
  • Frasier Syndrome / etiology
  • Genital Diseases, Male / etiology
  • Gonadotropins / blood
  • Hong Kong
  • Humans
  • Hypospadias / etiology
  • Infant
  • Infant, Newborn
  • Male
  • Mullerian Ducts / abnormalities
  • Mutation
  • Penis / abnormalities
  • Puberty, Delayed / etiology
  • Steroidogenic Factor 1 / genetics
  • Testosterone / blood


  • Gonadotropins
  • NR5A1 protein, human
  • Steroidogenic Factor 1
  • Dihydrotestosterone
  • Testosterone
  • Cholesterol Side-Chain Cleavage Enzyme
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • steroid-5alpha-reductase type 2

Supplementary concepts

  • Mullerian aplasia
  • Penis agenesis