U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

46,XX sex reversal 4(SRXX4)

MedGen UID:
1373282
Concept ID:
C4479552
Congenital Abnormality
Synonyms: 46, XX sex reversal 4; 46,XX SEX REVERSAL, SRY-NEGATIVE; SRXX4
 
Gene (location): NR5A1 (9q33.3)
 
Monarch Initiative: MONDO:0060489
OMIM®: 617480

Disease characteristics

Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency. [from GeneReviews]
Authors:
Emmanuèle C Délot  |  Eric J Vilain   view full author information

Clinical features

From HPO
Gonadal dysgenesis
MedGen UID:
9075
Concept ID:
C0018051
Congenital Abnormality
A congenital disorder characterized by the presence of extremely hypoplastic gonads preventing the development of secondary sex characteristics.
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Ambiguous genitalia
MedGen UID:
78596
Concept ID:
C0266362
Congenital Abnormality
A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale
Penoscrotal hypospadias
MedGen UID:
105291
Concept ID:
C0452147
Congenital Abnormality
A severe form of hypospadias in which the urethral opening is located at the junction of the penis and scrotum.
Retractile testis
MedGen UID:
636075
Concept ID:
C0520578
Congenital Abnormality
A testis that is located at the upper scrotum or lower inguinal canal and that can be made to descend completely into the scrotum without resistance by manual reduction but returns to its original position by the cremasteric reflex.
Fused labia majora
MedGen UID:
1383259
Concept ID:
C4476806
Anatomical Abnormality
The outer labia are sealed together.
Ovotestis
MedGen UID:
1634511
Concept ID:
C4551490
Congenital Abnormality
A gonad that contains both ovarian follicles and testicular tubular elements.
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.

Professional guidelines

PubMed

Banerjee B, Dutta A, Roy S, Halder A
J Obstet Gynaecol 2024 Dec;44(1):2348085. Epub 2024 May 6 doi: 10.1080/01443615.2024.2348085. PMID: 38708796
Pinhas-Hamiel O, Zalel Y, Smith E, Mazkereth R, Aviram A, Lipitz S, Achiron R
J Clin Endocrinol Metab 2002 Oct;87(10):4547-53. doi: 10.1210/jc.2001-011034. PMID: 12364433

Recent clinical studies

Etiology

Berglund A, Johannsen TH, Stochholm K, Aksglaede L, Fedder J, Viuff MH, Main KM, Gravholt CH
Hum Reprod 2017 Aug 1;32(8):1751-1760. doi: 10.1093/humrep/dex210. PMID: 28854582
Chan AO, But WM, Lee CY, Lam YY, Ng KL, Loung PY, Lam A, Cheng CW, Shek CC, Wong WS, Wong KF, Wong MY, Tse WY
Hong Kong Med J 2015 Dec;21(6):499-510. Epub 2015 Oct 16 doi: 10.12809/hkmj144402. PMID: 26492835
Kim GJ, Sock E, Buchberger A, Just W, Denzer F, Hoepffner W, German J, Cole T, Mann J, Seguin JH, Zipf W, Costigan C, Schmiady H, Rostásy M, Kramer M, Kaltenbach S, Rösler B, Georg I, Troppmann E, Teichmann AC, Salfelder A, Widholz SA, Wieacker P, Hiort O, Camerino G, Radi O, Wegner M, Arnold HH, Scherer G
J Med Genet 2015 Apr;52(4):240-7. Epub 2015 Jan 20 doi: 10.1136/jmedgenet-2014-102864. PMID: 25604083
Janner M, Flück CE, Mullis PE
Horm Res Paediatr 2012;78(4):261-8. Epub 2012 Sep 6 doi: 10.1159/000341585. PMID: 22964562
Rall K, Barresi G, Walter M, Poths S, Haebig K, Schaeferhoff K, Schoenfisch B, Riess O, Wallwiener D, Bonin M, Brucker S
Orphanet J Rare Dis 2011 May 28;6:32. doi: 10.1186/1750-1172-6-32. PMID: 21619687Free PMC Article

Diagnosis

Banerjee B, Dutta A, Roy S, Halder A
J Obstet Gynaecol 2024 Dec;44(1):2348085. Epub 2024 May 6 doi: 10.1080/01443615.2024.2348085. PMID: 38708796
Tallapaka K, Venugopal V, Dalal A, Aggarwal S
Am J Med Genet A 2018 Apr;176(4):1006-1010. doi: 10.1002/ajmg.a.38646. PMID: 29575617
Berglund A, Johannsen TH, Stochholm K, Aksglaede L, Fedder J, Viuff MH, Main KM, Gravholt CH
Hum Reprod 2017 Aug 1;32(8):1751-1760. doi: 10.1093/humrep/dex210. PMID: 28854582
Pinhas-Hamiel O, Zalel Y, Smith E, Mazkereth R, Aviram A, Lipitz S, Achiron R
J Clin Endocrinol Metab 2002 Oct;87(10):4547-53. doi: 10.1210/jc.2001-011034. PMID: 12364433
Yamamoto M, Yokoi K, Katsuno S, Hibi H, Miyake K
Nagoya J Med Sci 1995 Dec;58(3-4):111-5. PMID: 8725494

Therapy

Berglund A, Johannsen TH, Stochholm K, Aksglaede L, Fedder J, Viuff MH, Main KM, Gravholt CH
Hum Reprod 2017 Aug 1;32(8):1751-1760. doi: 10.1093/humrep/dex210. PMID: 28854582
Chen L, Ding XP, Wei X, Li LX
Genet Mol Res 2014 Mar 12;13(1):1518-26. doi: 10.4238/2014.March.12.4. PMID: 24668626
Janner M, Flück CE, Mullis PE
Horm Res Paediatr 2012;78(4):261-8. Epub 2012 Sep 6 doi: 10.1159/000341585. PMID: 22964562

Prognosis

Berglund A, Johannsen TH, Stochholm K, Aksglaede L, Fedder J, Viuff MH, Main KM, Gravholt CH
Hum Reprod 2017 Aug 1;32(8):1751-1760. doi: 10.1093/humrep/dex210. PMID: 28854582
Janner M, Flück CE, Mullis PE
Horm Res Paediatr 2012;78(4):261-8. Epub 2012 Sep 6 doi: 10.1159/000341585. PMID: 22964562

Clinical prediction guides

Wei J, Liu C, Zhang M, Liu S, Fu J, Lin P
BMC Med Genomics 2022 Sep 5;15(1):188. doi: 10.1186/s12920-022-01347-0. PMID: 36064700Free PMC Article
Orekhova AS, Kalinchenko N, Morozov IA, Vasilyev EV, Rubtsov PM, Dedov II, Tiulpakov A
Horm Res Paediatr 2018;89(6):450-454. Epub 2017 Nov 17 doi: 10.1159/000481776. PMID: 29151085
Nagata T, Kawano A, Koyama M, Nakamura T, Hirahara F, Nakajima T, Sato T, Sakakibara H
J Pediatr Adolesc Gynecol 2017 Jun;30(3):400-404. Epub 2015 Dec 11 doi: 10.1016/j.jpag.2015.12.001. PMID: 26688428
Janner M, Flück CE, Mullis PE
Horm Res Paediatr 2012;78(4):261-8. Epub 2012 Sep 6 doi: 10.1159/000341585. PMID: 22964562
Pinhas-Hamiel O, Zalel Y, Smith E, Mazkereth R, Aviram A, Lipitz S, Achiron R
J Clin Endocrinol Metab 2002 Oct;87(10):4547-53. doi: 10.1210/jc.2001-011034. PMID: 12364433

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...