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46,XY sex reversal 4(SRXY4)

MedGen UID:
416704
Concept ID:
C2752149
Congenital Abnormality
Synonyms: 46,XY GONADAL DYSGENESIS, PARTIAL OR COMPLETE, WITH 9p24.3 DELETION; CHROMOSOME 9p24.3 DELETION SYNDROME
 
Monarch Initiative: MONDO:0007938
OMIM®: 154230

Definition

Sex reversal in an individual associated with a 9p24.3 deletion. [from NCI]

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.
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Uterine hypoplasia
MedGen UID:
120575
Concept ID:
C0266399
Congenital Abnormality
Underdevelopment of the uterus.
Ureteropelvic junction obstruction
MedGen UID:
105482
Concept ID:
C0521619
Anatomical Abnormality
Blockage of urine flow from the renal pelvis to the proximal ureter.
Hypoplastic labia majora
MedGen UID:
107566
Concept ID:
C0566899
Finding
Undergrowth of the outer labia.
Agonadism
MedGen UID:
899272
Concept ID:
C2118097
Disease or Syndrome
Absence of sex glands (gonads are the organs that produce gametes; testis in males and ovary in females).
Renal dysplasia
MedGen UID:
760690
Concept ID:
C3536714
Congenital Abnormality
The presence of developmental dysplasia of the kidney.
Sex reversal
MedGen UID:
868596
Concept ID:
C4022995
Finding
Development of the reproductive system is inconsistent with the chromosomal sex.
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
Distal symphalangism
MedGen UID:
350018
Concept ID:
C1861401
Congenital Abnormality
Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or the feet (summary by Poush, 1991).
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Increased blood urea nitrogen
MedGen UID:
760252
Concept ID:
C0151539
Finding
An increased amount of nitrogen in the form of urea in the blood.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Depressed nasal ridge
MedGen UID:
334631
Concept ID:
C1842876
Finding
Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
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.

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

Recent clinical studies

Etiology

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
Zhu J, Liu X, Jin H, Lu X
Clin Exp Obstet Gynecol 2011;38(4):414-8. PMID: 22268289
Ismail SI, Mazen IA
Sex Dev 2010 Sep;4(4-5):285-91. Epub 2010 Jul 24 doi: 10.1159/000317120. PMID: 20664246
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
Croft B, Bird AD, Ono M, Eggers S, Bagheri-Fam S, Ryan JM, Reyes AP, van den Bergen J, Baxendale A, Thompson EM, Kueh AJ, Stanton P, Thomas T, Sinclair AH, Harley VR
Clin Genet 2023 Mar;103(3):277-287. Epub 2022 Nov 28 doi: 10.1111/cge.14261. PMID: 36349847Free PMC Article
Zhu J, Liu X, Jin H, Lu X
Clin Exp Obstet Gynecol 2011;38(4):414-8. PMID: 22268289
Dai YL, Fu JF, Hong F, Xu S, Shen Z
Acta Paediatr 2011 Jul;100(7):e39-42. Epub 2011 Feb 14 doi: 10.1111/j.1651-2227.2011.02167.x. PMID: 21314844
Telvi L, Lebbar A, Del Pino O, Barbet JP, Chaussain JL
Pediatrics 1999 Aug;104(2 Pt 1):304-8. doi: 10.1542/peds.104.2.304. PMID: 10429013

Therapy

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
Fenzl V, Duić Z, Popić-Ramac J, Skrtić A
Acta Clin Croat 2011 Dec;50(4):603-7. PMID: 22649894
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

Prognosis

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
Ottolenghi C, Veitia R, Barbieri M, Fellous M, McElreavey K
Genomics 2000 Mar 1;64(2):179-86. doi: 10.1006/geno.2000.6120. PMID: 10729224

Clinical prediction guides

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
Joshi R, Das D, Tamhankar P, Shaikh S
Indian Pediatr 2014 May;51(5):399-400. PMID: 24953586
Chen YS, Racca JD, Phillips NB, Weiss MA
Proc Natl Acad Sci U S A 2013 Sep 17;110(38):E3567-76. Epub 2013 Sep 3 doi: 10.1073/pnas.1300828110. PMID: 24003159Free PMC Article
Rajender S, Thangaraj K, Gupta NJ, Leelavathy N, Rani DS, Nambiar RG, Kalavathy V, Santhiya ST, Rajangam S, Gopinath PM, Chakravarty B, Singh L
J Clin Endocrinol Metab 2006 Oct;91(10):4028-36. Epub 2006 Jul 25 doi: 10.1210/jc.2006-0950. PMID: 16868052
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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