5-Alpha Reductase Deficiency

5-Alpha Reductase Deficiency is a 46,XY disorder of sex development (DSD) caused by reduced or absent function of the steroid 5-alpha reductase type 2 enzyme, which converts testosterone (T) into dihydrotestosterone (DHT) during embryogenesis. Individuals with 5-alpha reductase deficiency have normal Wolffian duct differentiation, but at birth the appearance of the external genitalia ranges from normal female to undermasculinized male. The classic presentation is ambiguous genitalia characterized by perineoscrotal hypospadias with pseudovagina, microphallus, and cryptorchidism. A recent study indicated that the most common phenotype is cliteromegaly, which was present in ~50% of individuals, followed by hypospadias associated with microphallus, which was reported in ~33% of patients (Maimoun et al., 2011). While most patients have ambiguous genitalia noted in infancy, individuals with female external genitalia may not present until puberty with primary amenorrhea, a lack of breast development, and virilization of the external genitalia. If the diagnosis of 5-alpha reductase deficiency is not made in infancy, the majority of infants are assigned a female gender based on the appearance of the external genitalia; however, significant virilization of the external genitalia occurs at puberty unless a gonadectomy is performed. An estimated 56-63% of individuals with 5-alpha reductase deficiency that are assigned a female gender have been reported to change to male gender identity at puberty (Cohen-Kettenis et al., 2005), so early diagnosis is important to assist with gender assignment. While most patients with 5-alpha reductase deficiency exhibit abnormally high levels of baseline and/or hCG-stimulated T:DHT ratios, individuals with partial enzyme deficiencies have been reported with normal T:DHT ratios. Therefore, in some cases it can be difficult to differentiate 5-alpha reductase deficiency from partial androgen insensitivity syndrome (AIS) and other 46,XY disorders of sex differentiation based on clinical and biochemical studies.

Tests Available

Forms and Documents

Test Details

SRD5A2
  • Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of 46,XY disorder of sex development
  • Mutation-specific testing for fetuses with a family history of known SRD5A2 mutations
  • Capillary Sequencing

Ordering

702
2-3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81479x1, 81265x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Maimoun et al., (2011) J Clin Endocrinol Metab 96:296-307.
  2. Thigpen et al., (1992) J Clin Invest 90:799-809.
  3. Hackel et al., (2005) J Mol Med 83:569-576.
  4. Vilchis et al., (2010) J Androl 31:358-364.
  5. Sasaki et al., (2003) J Clin Endocrinol Metab 88:3431-3436.
  6. Wang et al., (2004) Eur J Hum Genet 12:706-712.
  7. Andersson et al., (1991) Nature 354:159-161.
  8. Mazen et al., (2003) Clin Endocrinol 58:627-631.
  9. Makridakis et al., (1997) Cancer Res 57:1020-1022.