Editing 5α-Reductase 2 deficiency (section)

==Signs and symptoms==
Affected individuals exhibit a broad spectrum of presentation including atypical genitalia (ranging from female-appearing to underutilized male), [[hypospadias]], and isolated [[micropenis]]. The internal reproductive structures ([[vasa deferentia]], [[seminal vesicles]], [[epididymides]] and [[ejaculatory ducts]]) are normal but [[testes]] are usually undescended and [[prostate hypoplasia]] is common. Males with the same mutations in SRD5A2 can have different phenotypes suggesting additional factors that are involved in clinical presentation.<ref name="Mendonca2016">{{cite journal |last1=Mendonca |first1=Berenice B. |last2=Batista |first2=Rafael Loch |last3=Domenice |first3=Sorahia |last4=Costa |first4=Elaine M.F. |last5=Arnhold |first5=Ivo J.P. |last6=Russell |first6=David W. |last7=Wilson |first7=Jean D. |title=Steroid 5α-reductase 2 deficiency |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=October 2016 |volume=163 |pages=206–211 |doi=10.1016/j.jsbmb.2016.05.020|pmid=27224879 |s2cid=26748233 }}</ref><ref name="Imperato-McGinley2002">{{cite journal |last1=Imperato-McGinley |first1=J |last2=Zhu |first2=Y.-S |title=Androgens and male physiology the syndrome of 5α-reductase-2 deficiency |journal=Molecular and Cellular Endocrinology |date=December 2002 |volume=198 |issue=1–2 |pages=51–59 |doi=10.1016/s0303-7207(02)00368-4|pmid=12573814 |s2cid=54356569 }}</ref> Although people who are genetically female (with two X chromosomes in each cell) may inherit variants in both copies of the SRD5A2 gene, their sexual development is not affected. The development of female sex characteristics does not require DHT, so a lack of steroid 5-alpha reductase 2 activity does not cause physical changes in these individuals.<ref name="MedlinePlus">{{cite web | title=5-alpha reductase deficiency: MedlinePlus Genetics | website=MedlinePlus | date=April 1, 2017 | url=https://medlineplus.gov/genetics/condition/5-alpha-reductase-deficiency/ | access-date=December 11, 2023}}</ref>

[[Virilization]] of genitalia with voice deepening, development of muscle mass occurs at puberty in affected individuals, and height is not impaired. [[Gynecomastia]] is uncommon and bone density is normal in contrast to 46,XY DSD from other causes such as [[partial androgen insensitivity syndrome]] and [[17β-hydroxysteroid dehydrogenase 3 deficiency]]. Hair on the face and body is reduced and [[male pattern baldness]] does not occur.<ref name="Mendonca2016"/>

Spontaneous fertility in 5αR2D affected individuals is very unusual<ref name="Mendonca2016"/> (though has been observed<ref name="Recent Studies on the Mechanism of">{{cite journal |last1=Deykin |first1=Daniel |last2=Balko |first2=Christine |last3=Wilson |first3=Jean D. |title=Recent Studies on the Mechanism of Action of Testosterone |journal=New England Journal of Medicine |date=21 December 1972 |volume=287 |issue=25 |pages=1284–1291 |doi=10.1056/NEJM197212212872508|pmid=4119318 }}</ref>) due to semen abnormalities that include reduced sperm counts, high semen viscosity and, in some cases, lack of primary spermatocytes. This supports the notion that DHT has an important role in spermatocyte differentiation.<ref>{{cite journal |last1=Costa |first1=Elaine |last2=Domenice |first2=Sorahia |last3=Sircili |first3=Maria |last4=Inacio |first4=Marlene |last5=Mendonca |first5=Berenice |title=DSD Due to 5α-Reductase 2 Deficiency&nbsp;— from Diagnosis to Long Term Outcome |journal=Seminars in Reproductive Medicine |date=8 October 2012 |volume=30 |issue=5 |pages=427–431 |doi=10.1055/s-0032-1324727|pmid=23044880 |s2cid=5289961 }}</ref> The broad spectrum of presentation is consistent with highly varying sperm counts among affected individuals. Testicular function may also be impaired by incomplete descent as well as the genetic mutation itself.<ref name="Cheon2011"/>