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XXXY and XXXXY Syndrome

MedGen UID:
416028
•Concept ID:
C2827598
•
Disease or Syndrome

Definition

Rare syndromes caused by chromosomal defects and characterized by the presence of multiple X chromosomes and one Y chromosome. Signs and symptoms include short stature, mental retardation, hypogonadism, undescended testes, gynecomastia, and hypotonia. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVXXXY and XXXXY Syndrome

Professional guidelines

PubMed

Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive Azoospermia and Klinefelter Syndrome Patients.
Kim SY, Lee BY, Oh AR, Park SY, Lee HS, Seo JT
Cytogenet Genome Res 2017;153(4):190-197. Epub 2018 Feb 22 doi: 10.1159/000487039. PMID: 29466784
A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene.
Ottesen AM, Garn ID, Aksglaede L, Juul A, Rajpert-De Meyts E
Mol Hum Reprod 2007 Oct;13(10):745-50. Epub 2007 Aug 24 doi: 10.1093/molehr/gam053. PMID: 17720778

Recent clinical studies

Etiology

Autism spectrum disorder associated with 49,XYYYY: case report and review of the literature.
Demily C, Poisson A, Peyroux E, Gatellier V, Nicolas A, Rigard C, Schluth-Bolard C, Sanlaville D, Rossi M
BMC Med Genet 2017 Jan 31;18(1):9. doi: 10.1186/s12881-017-0371-1. PMID: 28137251Free PMC Article
Chromosomal variants in klinefelter syndrome.
Frühmesser A, Kotzot D
Sex Dev 2011;5(3):109-23. Epub 2011 Apr 29 doi: 10.1159/000327324. PMID: 21540567
Klinefelter syndrome and other sex chromosomal aneuploidies.
Visootsak J, Graham JM Jr
Orphanet J Rare Dis 2006 Oct 24;1:42. doi: 10.1186/1750-1172-1-42. PMID: 17062147Free PMC Article
Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation.
Samango-Sprouse C
Semin Reprod Med 2001 Jun;19(2):193-202. doi: 10.1055/s-2001-15400. PMID: 11480917
The XXXXY sex chromosome abnormality.
BARR ML, CARR DH, POZSONYI J, WILSON RA, DUNN HG, JACOBSON TS, MILLER JR, LEWIS M, CHOWN B
Can Med Assoc J 1962 Oct 27;87(17):891-901. PMID: 13969480Free PMC Article

Diagnosis

48, XXXY/49, XXXXY mosaic: new neuroradiological features in an ultra-rare syndrome.
Milani D, Bonarrigo F, Avignone S, Triulzi F, Esposito S
Ital J Pediatr 2015 Jul 14;41:50. doi: 10.1186/s13052-015-0156-0. PMID: 26168786Free PMC Article
Chromosomal variants in klinefelter syndrome.
Frühmesser A, Kotzot D
Sex Dev 2011;5(3):109-23. Epub 2011 Apr 29 doi: 10.1159/000327324. PMID: 21540567
48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome.
Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P
Acta Paediatr 2011 Jun;100(6):851-60. Epub 2011 Apr 8 doi: 10.1111/j.1651-2227.2011.02235.x. PMID: 21342258Free PMC Article
Klinefelter syndrome and other sex chromosomal aneuploidies.
Visootsak J, Graham JM Jr
Orphanet J Rare Dis 2006 Oct 24;1:42. doi: 10.1186/1750-1172-1-42. PMID: 17062147Free PMC Article
Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation.
Samango-Sprouse C
Semin Reprod Med 2001 Jun;19(2):193-202. doi: 10.1055/s-2001-15400. PMID: 11480917

Therapy

Klinefelter Syndrome (49, XXXXY/48, XXXY) associated with narrow angle glaucoma: A case report.
Ulloa-Padilla EP, Dávila PJ, Izquierdo NJ
Bol Asoc Med P R 2016;108(1):85-90. PMID: 29193925
Association between venous leg ulcers and sex chromosome anomalies in men.
Gattringer C, Scheurecker C, Höpfl R, Müller H
Acta Derm Venereol 2010 Nov;90(6):612-5. doi: 10.2340/00015555-0949. PMID: 21057745
A case of Klinefelter's syndrome with 48,XXXY and diabetes mellitus.
Esmann V, Nielsen J, Petersen GB
Acta Med Scand 1969 Jul-Aug;186(1-2):27-33. doi: 10.1111/j.0954-6820.1969.tb01434.x. PMID: 5317784

Prognosis

Methylation-specific PCR allows for fast diagnosis of X chromosome disomy and reveals skewed inactivation of the X chromosome in men with Klinefelter syndrome.
Mehta A, Malek-Jones M, Bolyakov A, Mielnik A, Schlegel PN, Paduch DA
J Androl 2012 Sep-Oct;33(5):955-62. Epub 2012 Mar 22 doi: 10.2164/jandrol.111.016030. PMID: 22441764
Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation.
Samango-Sprouse C
Semin Reprod Med 2001 Jun;19(2):193-202. doi: 10.1055/s-2001-15400. PMID: 11480917
Bilateral breast tumors, malignant phyllodes tumor and invasive lobular carcinoma in a 46,XX/46,XY mosaic female with family history of breast cancer.
Kasami M, Yoshida M, Isogaki J, Ogawa H, Shinmura K, Endo Y, Kiyokawa E, Naito Y, Arai T, Kimura T, Inoue R, Sugimura H
Pathol Int 1997 Feb-Mar;47(2-3):147-54. doi: 10.1111/j.1440-1827.1997.tb03732.x. PMID: 9088032
Cytogenetic studies in a selected group of mentally retarded children.
Moghe M, Patel ZM, Peter JJ, Ambani LM
Hum Genet 1981;58(2):184-7. doi: 10.1007/BF00278708. PMID: 6456981

Clinical prediction guides

A rare variant Klinefelter syndrome seen 40 years later: 47,X,del(Xq24),Y.
Özkent MS, Balasar Ö
Andrologia 2021 Dec;53(11):e14213. Epub 2021 Aug 10 doi: 10.1111/and.14213. PMID: 34375016
Autism spectrum disorder associated with 49,XYYYY: case report and review of the literature.
Demily C, Poisson A, Peyroux E, Gatellier V, Nicolas A, Rigard C, Schluth-Bolard C, Sanlaville D, Rossi M
BMC Med Genet 2017 Jan 31;18(1):9. doi: 10.1186/s12881-017-0371-1. PMID: 28137251Free PMC Article
48, XXXY/49, XXXXY mosaic: new neuroradiological features in an ultra-rare syndrome.
Milani D, Bonarrigo F, Avignone S, Triulzi F, Esposito S
Ital J Pediatr 2015 Jul 14;41:50. doi: 10.1186/s13052-015-0156-0. PMID: 26168786Free PMC Article
Chromosomal variants in klinefelter syndrome.
Frühmesser A, Kotzot D
Sex Dev 2011;5(3):109-23. Epub 2011 Apr 29 doi: 10.1159/000327324. PMID: 21540567
Klinefelter's syndrome, mosaic 46,XX/46,XY/47,XXY/48,XXXY/48,XXYY: a case report.
Al-Awadi SA, Teebi AS, Krishna Murthy DS, Othman G, Sundareshan TS
Ann Genet 1986;29(2):119-21. PMID: 3490207

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