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46,XY sex reversal 1(TDFX, FORMERLY; SRVX, FORMERLY; SRXY1)

MedGen UID:
412662
Concept ID:
C2748896
Disease or Syndrome
Synonyms: 46,XY SEX REVERSAL, SRY-RELATED; SRY-related 46,XY complete gonadal dysgenesis
 
Gene (location): SRY (Yp11.2)
 
Monarch Initiative: MONDO:0020712
OMIM®: 400044

Definition

Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein. [from NCI]

Clinical features

From HPO
Gonadoblastoma
MedGen UID:
104912
Concept ID:
C0206661
Neoplastic Process
The presence of a gonadoblastoma, a neoplasm of a gonad that consists of aggregates of germ cells and sex cord elements.
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.
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Male pseudohermaphroditism
MedGen UID:
68666
Concept ID:
C0238395
Congenital Abnormality
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In male pseudohermaphroditism, the genotype is male (XY) and the external genitalia are imcompletely virilized, ambiguous, or complete female. If gonads are present, they are testes.
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
Abnormal female external genitalia morphology
MedGen UID:
867445
Concept ID:
C4021822
Anatomical Abnormality
Any structural abnormality of the female external genitalia.
Sex reversal
MedGen UID:
868596
Concept ID:
C4022995
Finding
Development of the reproductive system is inconsistent with the chromosomal sex.
Gonadal dysgenesis with female appearance, male
MedGen UID:
893083
Concept ID:
C4024632
Congenital Abnormality
Unusual gonadal development in a person with a 46,XY male karyotype, leading to a more female sex differentiation.
Abnormality of the menstrual cycle
MedGen UID:
893088
Concept ID:
C4025888
Finding
An abnormality of the ovulation cycle.
Abnormal male external genitalia morphology
MedGen UID:
871399
Concept ID:
C4025897
Anatomical Abnormality
Any structural abnormality of male external genitalia.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
Elevated circulating follicle stimulating hormone level
MedGen UID:
867192
Concept ID:
C4021550
Finding
An elevated concentration of follicle-stimulating hormone in the blood.
Absence of secondary sex characteristics
MedGen UID:
867193
Concept ID:
C4021551
Finding
No secondary sexual characteristics are present at puberty.
Elevated circulating luteinizing hormone level
MedGen UID:
868698
Concept ID:
C4023101
Finding
An elevated concentration of luteinizing hormone in the blood.

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
Gui B, Song Y, Su Z, Luo FH, Chen L, Wang X, Chen R, Yang Y, Wang J, Zhao X, Fan L, Liu X, Wang Y, Chen S, Gong C
J Med Genet 2019 Oct;56(10):685-692. Epub 2019 Jun 11 doi: 10.1136/jmedgenet-2018-105915. PMID: 31186340
Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, Ishii T, Numakura C, Sawada H, Nakacho M, Kowase T, Motomura K, Haruna H, Nakamura M, Ohishi A, Adachi M, Tajima T, Hasegawa Y, Hasegawa T, Horikawa R, Fujieda K, Ogata T
J Clin Endocrinol Metab 2009 May;94(5):1723-31. Epub 2009 Mar 3 doi: 10.1210/jc.2008-2816. PMID: 19258400

Recent clinical studies

Etiology

Rjiba K, Slimani W, Gaddas M, Hassine IH, Jelloul A, Khelifa HB, El Amri F, Zaouali M, Mcelreavey K, Saad A, Mougou-Zerelli S
J Clin Res Pediatr Endocrinol 2023 Feb 27;15(1):25-34. Epub 2022 Aug 19 doi: 10.4274/jcrpe.galenos.2022.2022-3-15. PMID: 35984215Free PMC Article
Craver R, Stark M, Moss S, Long S, Prasad P, C Roth C
Fetal Pediatr Pathol 2023 Feb;42(1):63-71. Epub 2022 Feb 24 doi: 10.1080/15513815.2022.2043962. PMID: 35199613
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
Geckinli BB, Toksoy G, Sayar C, Soylemez MA, Yesil G, Aydın H, Karaman A, Devranoglu B
Eur J Obstet Gynecol Reprod Biol 2014 Nov;182:211-5. Epub 2014 Sep 28 doi: 10.1016/j.ejogrb.2014.09.033. PMID: 25445102
Ostrer H
Clin Genet 2001 Apr;59(4):207-15. doi: 10.1034/j.1399-0004.2001.590401.x. PMID: 11298673

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
Rjiba K, Slimani W, Gaddas M, Hassine IH, Jelloul A, Khelifa HB, El Amri F, Zaouali M, Mcelreavey K, Saad A, Mougou-Zerelli S
J Clin Res Pediatr Endocrinol 2023 Feb 27;15(1):25-34. Epub 2022 Aug 19 doi: 10.4274/jcrpe.galenos.2022.2022-3-15. PMID: 35984215Free PMC Article
Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Ozisik G, Achermann JC, Meeks JJ, Jameson JL
Horm Res 2003;59 Suppl 1:94-8. doi: 10.1159/000067831. PMID: 12566727
Baumstark A, Barbi G, Djalali M, Geerkens C, Mitulla B, Mattfeldt T, de Almeida JC, Vargas FR, Llerena Júnior JC, Vogel W, Just W
Hum Genet 1996 Jan;97(1):79-86. doi: 10.1007/BF00218838. PMID: 8557267

Therapy

Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
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
Gaspari L, Paris F, Philibert P, Audran F, Orsini M, Servant N, Maïmoun L, Kalfa N, Sultan C
Eur J Endocrinol 2011 Oct;165(4):579-87. Epub 2011 Jul 25 doi: 10.1530/EJE-11-0580. PMID: 21788424
Birnbacher R, Marberger M, Weissenbacher G, Schober E, Frisch H
J Pediatr Endocrinol Metab 1999 Sep-Oct;12(5):687-90. doi: 10.1515/jpem.1999.12.5.687. PMID: 10703543
Kim MR, Qazi QH, Anderson VM, Valencia GB
Am J Obstet Gynecol 1995 Mar;172(3):1042-3. doi: 10.1016/0002-9378(95)90042-x. PMID: 7892846

Prognosis

Faridi R, Yousaf R, Inagaki S, Olszewski R, Gu S, Morell RJ, Wilson E, Xia Y, Qaiser TA, Rashid M, Fenollar-Ferrer C, Hoa M, Riazuddin S, Friedman TB
Genes (Basel) 2024 Jun 27;15(7) doi: 10.3390/genes15070845. PMID: 39062623Free PMC Article
Kırkgöz T, Gürsoy S, Acar S, Köprülü Ö, Özkaya B, Arslan G, Nalbantoğlu Ö, Hazan F, Özkan B
J Pediatr Endocrinol Metab 2024 Jun 25;37(6):575-579. Epub 2024 Apr 23 doi: 10.1515/jpem-2023-0551. PMID: 38650427
Stoeva R, Grozdanova L, Scherer G, Krasteva M, Bausch E, Krastev T, Linev A, Stefanova M
Genet Couns 2011;22(1):49-53. PMID: 21614988
Hiort O, Holterhus PM, Werner R, Marschke C, Hoppe U, Partsch CJ, Riepe FG, Achermann JC, Struve D
J Clin Endocrinol Metab 2005 Jan;90(1):538-41. Epub 2004 Oct 26 doi: 10.1210/jc.2004-1059. PMID: 15507506
Ninomiya S, Narahara K, Tsuji K, Yokoyama Y, Ito S, Seino Y
Am J Med Genet 1995 Mar 13;56(1):31-4. doi: 10.1002/ajmg.1320560109. PMID: 7747782

Clinical prediction guides

Rjiba K, Slimani W, Gaddas M, Hassine IH, Jelloul A, Khelifa HB, El Amri F, Zaouali M, Mcelreavey K, Saad A, Mougou-Zerelli S
J Clin Res Pediatr Endocrinol 2023 Feb 27;15(1):25-34. Epub 2022 Aug 19 doi: 10.4274/jcrpe.galenos.2022.2022-3-15. PMID: 35984215Free PMC Article
Livermore C, Simon M, Reeves R, Stévant I, Nef S, Pope M, Mallon AM, Wells S, Warr N, Greenfield A
Genetics 2020 Feb;214(2):467-477. Epub 2019 Dec 13 doi: 10.1534/genetics.119.302786. PMID: 31836612Free PMC Article
Onesimo R, Orteschi D, Scalzone M, Rossodivita A, Nanni L, Zannoni GF, Marrocco G, Battaglia D, Fundarò C, Neri G
Am J Med Genet A 2012 Sep;158A(9):2266-71. Epub 2012 Jul 20 doi: 10.1002/ajmg.a.35489. PMID: 22821627
Ergun-Longmire B, Vinci G, Alonso L, Matthew S, Tansil S, Lin-Su K, McElreavey K, New MI
J Pediatr Endocrinol Metab 2005 Aug;18(8):739-48. doi: 10.1515/jpem.2005.18.8.739. PMID: 16200839
Ostrer H
Clin Genet 2001 Apr;59(4):207-15. doi: 10.1034/j.1399-0004.2001.590401.x. PMID: 11298673

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