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3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency(PPSH)

MedGen UID:
75667
Concept ID:
C0268297
Disease or Syndrome
Synonyms: 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency; FAMILIAL INCOMPLETE MALE PSEUDOHERMAPHRODITISM, TYPE 2; MALE PSEUDOHERMAPHRODITISM DUE TO 5-ALPHA-REDUCTASE DEFICIENCY; PPSH; PSEUDOVAGINAL PERINEOSCROTAL HYPOSPADIAS; Steroid 5-Alpha-Reductase Deficiency
SNOMED CT: Familial incomplete male pseudohermaphroditism type 2 (738771004); Pseudovaginal perineoscrotal hypospadias (738771004); Male pseudohermaphroditism due to 5-alpha-reductase deficiency (738771004); PPSH - Pseudovaginal perineoscrotal hypospadias (738771004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SRD5A2 (2p23.1)
 
Monarch Initiative: MONDO:0009923
OMIM®: 264600
Orphanet: ORPHA753

Definition

Pseudovaginal perineoscrotal hypospadias is a form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. [from OMIM]

Additional description

From MedlinePlus Genetics
5-alpha reductase deficiency is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.

Many people with 5-alpha reductase deficiency have external genitalia that appears female. In other cases, affected infants have male-typical external genitalia, often an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). Still other affected infants have external genitalia do not look clearly male or clearly female.

During puberty, an increase in the levels of male sex hormones leads to the development of some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) may grow larger. People with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected individuals are unable to have biological children (infertile) without assisted reproduction.  https://medlineplus.gov/genetics/condition/5-alpha-reductase-deficiency

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Abnormal hair morphology
MedGen UID:
56381
Concept ID:
C0157733
Finding
An abnormality of the hair.
Bifid scrotum
MedGen UID:
90968
Concept ID:
C0341787
Congenital Abnormality
Midline indentation or cleft of the scrotum.
Perineal hypospadias
MedGen UID:
105292
Concept ID:
C0452148
Congenital Abnormality
Hypospadias with location of the urethral meatus in the perineal region.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Abnormality of the voice
MedGen UID:
867406
Concept ID:
C4021776
Finding
Ambiguous genitalia, male
MedGen UID:
867446
Concept ID:
C4021823
Finding
Ambiguous genitalia in an individual with XY genetic gender.
Abnormality of the endocrine system
MedGen UID:
893021
Concept ID:
C4025823
Anatomical Abnormality
An abnormality of the endocrine system.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
Follow this link to review classifications for 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency in Orphanet.

Professional guidelines

PubMed

Wen X, Fan LJ, Zhang WP, Ni X, Gong CX
Asian J Androl 2023 Nov 1;25(6):731-736. Epub 2023 Jun 9 doi: 10.4103/aja202313. PMID: 37313883Free PMC Article
Alswailem MM, Alzahrani OS, Alghofaili L, Qasem E, Almohanaa M, Alsagheir A, Bin Abbas B, Attia NA, Al Shaikh A, Alzahrani AS
Endocrine 2019 Feb;63(2):361-368. Epub 2018 Sep 29 doi: 10.1007/s12020-018-1767-1. PMID: 30269266
Avendaño A, Paradisi I, Cammarata-Scalisi F, Callea M
Hormones (Athens) 2018 Jun;17(2):197-204. Epub 2018 Apr 20 doi: 10.1007/s42000-018-0013-9. PMID: 29858846

Recent clinical studies

Etiology

Liu Q, Yin X, Li P
Endocr Pract 2022 Sep;28(9):859-866. Epub 2022 Jun 11 doi: 10.1016/j.eprac.2022.06.002. PMID: 35700942
Sepulveda W, Seiltgens C, Betancourt E, Mangiamarchi M
Fetal Pediatr Pathol 2022 Oct;41(5):794-799. Epub 2021 Jul 12 doi: 10.1080/15513815.2021.1948645. PMID: 34251982
Alswailem MM, Alzahrani OS, Alghofaili L, Qasem E, Almohanaa M, Alsagheir A, Bin Abbas B, Attia NA, Al Shaikh A, Alzahrani AS
Endocrine 2019 Feb;63(2):361-368. Epub 2018 Sep 29 doi: 10.1007/s12020-018-1767-1. PMID: 30269266
Nascimento RLP, de Andrade Mesquita IM, Gondim R, Dos Apóstolos RAAC, Toralles MB, de Oliveira LB, Canguçu-Campinho AK, Barroso U Jr
J Pediatr Urol 2018 Oct;14(5):419.e1-419.e6. Epub 2018 Sep 5 doi: 10.1016/j.jpurol.2018.08.021. PMID: 30297225
Mendonca BB, Gomes NL, Costa EM, Inacio M, Martin RM, Nishi MY, Carvalho FM, Tibor FD, Domenice S
J Steroid Biochem Mol Biol 2017 Jan;165(Pt A):79-85. Epub 2016 May 6 doi: 10.1016/j.jsbmb.2016.05.002. PMID: 27163392

Diagnosis

Markouli M, Michala L
J Pediatr Urol 2023 Feb;19(1):108-114. Epub 2022 Sep 9 doi: 10.1016/j.jpurol.2022.09.002. PMID: 36153242
Alswailem MM, Alzahrani OS, Alghofaili L, Qasem E, Almohanaa M, Alsagheir A, Bin Abbas B, Attia NA, Al Shaikh A, Alzahrani AS
Endocrine 2019 Feb;63(2):361-368. Epub 2018 Sep 29 doi: 10.1007/s12020-018-1767-1. PMID: 30269266
Avendaño A, Paradisi I, Cammarata-Scalisi F, Callea M
Hormones (Athens) 2018 Jun;17(2):197-204. Epub 2018 Apr 20 doi: 10.1007/s42000-018-0013-9. PMID: 29858846
Mendonca BB, Gomes NL, Costa EM, Inacio M, Martin RM, Nishi MY, Carvalho FM, Tibor FD, Domenice S
J Steroid Biochem Mol Biol 2017 Jan;165(Pt A):79-85. Epub 2016 May 6 doi: 10.1016/j.jsbmb.2016.05.002. PMID: 27163392
Sultan C, Lumbroso S, Paris F, Jeandel C, Terouanne B, Belon C, Audran F, Poujol N, Georget V, Gobinet J, Jalaguier S, Auzou G, Nicolas JC
Semin Reprod Med 2002 Aug;20(3):217-28. doi: 10.1055/s-2002-35386. PMID: 12428202

Therapy

Levy B, Teplitsky S, Kalaitzoglou E, Kahler S, Matheny JP, Saltzman AF
Urology 2023 Aug;178:147-150. Epub 2023 May 11 doi: 10.1016/j.urology.2023.05.001. PMID: 37178876
Ariyasu D, Nagamatsu F, Aso K, Akiba K, Hasegawa Y
Endocr J 2023 Jan 30;70(1):59-67. Epub 2022 Oct 8 doi: 10.1507/endocrj.EJ22-0112. PMID: 36216557
Tran TCM, Tran TNA, Le HBN, Nguyen VH, Tran MD, Vu CD, Greaves RF
Clin Chem Lab Med 2022 Jul 26;60(8):1225-1233. Epub 2022 May 24 doi: 10.1515/cclm-2022-0272. PMID: 35607271
Sasaki G, Ishii T, Hori N, Amano N, Homma K, Sato S, Hasegawa T
Endocr J 2019 Sep 28;66(9):837-842. Epub 2019 Jun 8 doi: 10.1507/endocrj.EJ19-0111. PMID: 31178538

Prognosis

Zhang W, Yu B, Luo W, Sun B, Zhang X, Wang X, Mao J, Nie M, Wu X
J Steroid Biochem Mol Biol 2023 Dec;235:106421. Epub 2023 Oct 31 doi: 10.1016/j.jsbmb.2023.106421. PMID: 37918676
Seo J, Shin S, Kim SW, Kim SJ, Lee M, Song K, Suh J, Lee ST, Lee YS, Chae HW, Kim HS, Choi JR, Han S, Kwon A
Int J Mol Sci 2023 Feb 7;24(4) doi: 10.3390/ijms24043297. PMID: 36834714Free PMC Article
Ariyasu D, Nagamatsu F, Aso K, Akiba K, Hasegawa Y
Endocr J 2023 Jan 30;70(1):59-67. Epub 2022 Oct 8 doi: 10.1507/endocrj.EJ22-0112. PMID: 36216557
Sheikh WH, Asif N, Haroon ZH, Ejaz A, Ain QU, Shehzad N
J Pak Med Assoc 2019 Aug;69(8):1090-1093. PMID: 31431758
Sasaki G, Ishii T, Hori N, Amano N, Homma K, Sato S, Hasegawa T
Endocr J 2019 Sep 28;66(9):837-842. Epub 2019 Jun 8 doi: 10.1507/endocrj.EJ19-0111. PMID: 31178538

Clinical prediction guides

Zhang W, Yu B, Luo W, Sun B, Zhang X, Wang X, Mao J, Nie M, Wu X
J Steroid Biochem Mol Biol 2023 Dec;235:106421. Epub 2023 Oct 31 doi: 10.1016/j.jsbmb.2023.106421. PMID: 37918676
Wen X, Fan LJ, Zhang WP, Ni X, Gong CX
Asian J Androl 2023 Nov 1;25(6):731-736. Epub 2023 Jun 9 doi: 10.4103/aja202313. PMID: 37313883Free PMC Article
Liu Q, Yin X, Li P
Endocr Pract 2022 Sep;28(9):859-866. Epub 2022 Jun 11 doi: 10.1016/j.eprac.2022.06.002. PMID: 35700942
Avendaño A, Paradisi I, Cammarata-Scalisi F, Callea M
Hormones (Athens) 2018 Jun;17(2):197-204. Epub 2018 Apr 20 doi: 10.1007/s42000-018-0013-9. PMID: 29858846
Glenn JF
Urology 1976 Jun;7(6):569-77. doi: 10.1016/0090-4295(76)90079-0. PMID: 779212

Recent systematic reviews

Markouli M, Michala L
J Pediatr Urol 2023 Feb;19(1):108-114. Epub 2022 Sep 9 doi: 10.1016/j.jpurol.2022.09.002. PMID: 36153242
Islam R, Lane S, Williams SA, Becker CM, Conway GS, Creighton SM
Clin Endocrinol (Oxf) 2019 Aug;91(2):237-244. Epub 2019 May 2 doi: 10.1111/cen.13994. PMID: 31004515

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