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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 are assigned female at birth based on their external genitalia. In other cases, affected infants are assigned male at birth based on their external genitalia, often an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). Still other affected infants may be assigned either female or male at birth as their 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).
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.
Ambiguous genitalia, male
MedGen UID:
867446
Concept ID:
C4021823
Finding
Ambiguous genitalia in an individual with XY genetic gender.
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.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Abnormality of the voice
MedGen UID:
867406
Concept ID:
C4021776
Finding
Abnormal hair morphology
MedGen UID:
56381
Concept ID:
C0157733
Finding
An abnormality of the hair.
Abnormality of the endocrine system
MedGen UID:
893021
Concept ID:
C4025823
Anatomical Abnormality
An abnormality of the endocrine system.

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

Fan L, Song Y, Polak M, Li L, Ren X, Zhang B, Wu D, Gong C
Mol Genet Genomic Med 2020 Oct;8(10):e1431. Epub 2020 Jul 26 doi: 10.1002/mgg3.1431. PMID: 32713132Free 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

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
Mendonca BB, Batista RL, Domenice S, Costa EM, Arnhold IJ, Russell DW, Wilson JD
J Steroid Biochem Mol Biol 2016 Oct;163:206-11. Epub 2016 May 22 doi: 10.1016/j.jsbmb.2016.05.020. PMID: 27224879
Okeigwe I, Kuohung W
Curr Opin Endocrinol Diabetes Obes 2014 Dec;21(6):483-7. doi: 10.1097/MED.0000000000000116. PMID: 25321150

Diagnosis

Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
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
Imperato-McGinley J
Curr Ther Endocrinol Metab 1994;5:351-4. PMID: 7704752

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
Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
Canguven O, Burnett AL
J Androl 2008 Sep-Oct;29(5):514-23. Epub 2008 Apr 17 doi: 10.2164/jandrol.108.005025. PMID: 18421068
Kaufman KD
Mol Cell Endocrinol 2002 Dec 30;198(1-2):89-95. doi: 10.1016/s0303-7207(02)00372-6. PMID: 12573818
Ng WK, Taylor NF, Hughes IA, Taylor J, Ransley PG, Grant DB
Arch Dis Child 1990 Oct;65(10):1166-7. doi: 10.1136/adc.65.10.1166. PMID: 2248513Free PMC Article

Prognosis

Yoldas Celik M, Yazici H, Erdem F, Yuksel Yanbolu A, Aykut A, Durmaz A, Zeybek S, Canda E, Kalkan Ucar S, Coker M
J Pediatr Endocrinol Metab 2023 Jun 27;36(6):530-538. Epub 2023 Apr 13 doi: 10.1515/jpem-2022-0641. PMID: 37042760
Detlefsen AJ, Paulukinas RD, Penning TM
Int J Mol Sci 2023 Jan 18;24(3) doi: 10.3390/ijms24031873. PMID: 36768194Free PMC Article
Nistal M, Paniagua R, González-Peramato P, Reyes-Múgica M
Pediatr Dev Pathol 2015 Jul-Aug;18(4):279-96. Epub 2014 Aug 8 doi: 10.2350/14-04-1465-PB.1. PMID: 25105706
Costa EM, Domenice S, Sircili MH, Inacio M, Mendonca BB
Semin Reprod Med 2012 Oct;30(5):427-31. Epub 2012 Oct 8 doi: 10.1055/s-0032-1324727. PMID: 23044880
Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagami H, Liu M, Richards SM, Suzuki T, Schaumberg DA, Sullivan RM, Dana MR
Ann N Y Acad Sci 2002 Jun;966:211-22. doi: 10.1111/j.1749-6632.2002.tb04217.x. PMID: 12114274

Clinical prediction guides

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
Bertelloni S, Baldinotti F, Russo G, Ghirri P, Dati E, Michelucci A, Moscuzza F, Meroni S, Colombo I, Sessa MR, Baroncelli GI
Sex Dev 2016;10(1):28-36. Epub 2016 Apr 13 doi: 10.1159/000445090. PMID: 27070133
Nistal M, Paniagua R, González-Peramato P, Reyes-Múgica M
Pediatr Dev Pathol 2015 Jul-Aug;18(4):279-96. Epub 2014 Aug 8 doi: 10.2350/14-04-1465-PB.1. PMID: 25105706
Kaufman KD
Mol Cell Endocrinol 2002 Dec 30;198(1-2):89-95. doi: 10.1016/s0303-7207(02)00372-6. PMID: 12573818
Balducci R, Ghirri P, Brown TR, Bradford S, Boldrini A, Boscherini B, Sciarra F, Toscano V
Steroids 1996 Apr;61(4):205-11. doi: 10.1016/0039-128x(96)00015-3. PMID: 8733002

Recent systematic reviews

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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