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Four X syndrome

MedGen UID:
120544
Concept ID:
C0265496
Disease or Syndrome
Synonyms: 48 XXXX; 48 XXXX syndrome; Tetrasomy X
SNOMED CT: Four X syndrome (10567003); XXXX syndrome (10567003); Tetrasomy X (10567003)
 
Monarch Initiative: MONDO:0019525
Orphanet: ORPHA9

Definition

A sex chromosome anomaly caused by the presence of two extra X chromosomes in females (48,XXXX instead of 46,XX). This disorder is associated with delayed speech, learning difficulties, developmental delay and facial dysmorphism. Although disease severity is variable, the learning difficulties and developmental delay are generally mild to moderate. Commonly associated facial features include hypertelorism, upslanting palpebral fissures, epicanthal folds and a flat nasal bridge. Other anomalies may include dental abnormalities, hypotonia and joint laxity, radioulnar synostosis, heart defects, hip dysplasia, and ovarian dysfunction. An increased susceptibility to infections during childhood has also been reported. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFour X syndrome
Follow this link to review classifications for Four X syndrome in Orphanet.

Professional guidelines

PubMed

Soret P, Le Dantec C, Desvaux E, Foulquier N, Chassagnol B, Hubert S, Jamin C, Barturen G, Desachy G, Devauchelle-Pensec V, Boudjeniba C, Cornec D, Saraux A, Jousse-Joulin S, Barbarroja N, Rodríguez-Pintó I, De Langhe E, Beretta L, Chizzolini C, Kovács L, Witte T; PRECISESADS Clinical Consortium; PRECISESADS Flow Cytometry Consortium, Bettacchioli E, Buttgereit A, Makowska Z, Lesche R, Borghi MO, Martin J, Courtade-Gaiani S, Xuereb L, Guedj M, Moingeon P, Alarcón-Riquelme ME, Laigle L, Pers JO
Nat Commun 2021 Jun 10;12(1):3523. doi: 10.1038/s41467-021-23472-7. PMID: 34112769Free PMC Article
Farrugia FA, Martikos G, Tzanetis P, Charalampopoulos A, Misiakos E, Zavras N, Sotiropoulos D
Endocr Regul 2017 Jul 1;51(3):168-181. doi: 10.1515/enr-2017-0018. PMID: 28858847
Magini P, Palombo F, Boito S, Lanzoni G, Mongelli P, Rizzuti T, Baccarin M, Pippucci T, Seri M, Lalatta F
Am J Med Genet A 2016 Dec;170(12):3258-3264. Epub 2016 Sep 9 doi: 10.1002/ajmg.a.37873. PMID: 27612164

Recent clinical studies

Etiology

Shepherdson JL, Hutchison K, Don DW, McGillivray G, Choi TI, Allan CA, Amor DJ, Banka S, Basel DG, Buch LD, Carere DA, Carroll R, Clayton-Smith J, Crawford A, Dunø M, Faivre L, Gilfillan CP, Gold NB, Gripp KW, Hobson E, Holtz AM, Innes AM, Isidor B, Jackson A, Katsonis P, Amel Riazat Kesh L; Genomics England Research Consortium, Küry S, Lecoquierre F, Lockhart P, Maraval J, Matsumoto N, McCarrier J, McCarthy J, Miyake N, Moey LH, Németh AH, Østergaard E, Patel R, Pope K, Posey JE, Schnur RE, Shaw M, Stolerman E, Taylor JP, Wadman E, Wakeling E, White SM, Wong LC, Lupski JR, Lichtarge O, Corbett MA, Gecz J, Nicolet CM, Farnham PJ, Kim CH, Shinawi M
Am J Hum Genet 2024 Mar 7;111(3):487-508. Epub 2024 Feb 6 doi: 10.1016/j.ajhg.2024.01.007. PMID: 38325380Free PMC Article
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Lubs HA, Stevenson RE, Schwartz CE
Am J Hum Genet 2012 Apr 6;90(4):579-90. doi: 10.1016/j.ajhg.2012.02.018. PMID: 22482801Free PMC Article
Müller U
Brain 2009 Aug;132(Pt 8):2005-25. Epub 2009 Jul 3 doi: 10.1093/brain/awp172. PMID: 19578124
Hamel CP
Orphanet J Rare Dis 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7. PMID: 17270046Free PMC Article

Diagnosis

Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Graham JM Jr, Schwartz CE
Am J Med Genet A 2013 Nov;161A(11):2734-40. Epub 2013 Oct 10 doi: 10.1002/ajmg.a.36183. PMID: 24123922Free PMC Article
Lubs HA, Stevenson RE, Schwartz CE
Am J Hum Genet 2012 Apr 6;90(4):579-90. doi: 10.1016/j.ajhg.2012.02.018. PMID: 22482801Free PMC Article
Hamel CP
Orphanet J Rare Dis 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7. PMID: 17270046Free PMC Article
Singh AD, Rundle PA, Rennie I
Ophthalmol Clin North Am 2005 Mar;18(1):167-76, x. doi: 10.1016/j.ohc.2004.07.005. PMID: 15763202

Therapy

Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kühl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA
N Engl J Med 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442. PMID: 39383459
Jonkman AH, Alcala GC, Pavlovsky B, Roca O, Spadaro S, Scaramuzzo G, Chen L, Dianti J, Sousa MLA, Sklar MC, Piraino T, Ge H, Chen GQ, Zhou JX, Li J, Goligher EC, Costa E, Mancebo J, Mauri T, Amato M, Brochard LJ; Pleural Pressure Working Group (PLUG)
Am J Respir Crit Care Med 2023 Jul 1;208(1):25-38. doi: 10.1164/rccm.202212-2300OC. PMID: 37097986Free PMC Article
Sandsdal RM, Juhl CR, Jensen SBK, Lundgren JR, Janus C, Blond MB, Rosenkilde M, Bogh AF, Gliemann L, Jensen JB, Antoniades C, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS
Cardiovasc Diabetol 2023 Feb 25;22(1):41. doi: 10.1186/s12933-023-01765-z. PMID: 36841762Free PMC Article
Knight EMP, Amin S, Bahi-Buisson N, Benke TA, Cross JH, Demarest ST, Olson HE, Specchio N, Fleming TR, Aimetti AA, Gasior M, Devinsky O; Marigold Trial Group
Lancet Neurol 2022 May;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1. PMID: 35429480
Seidi F, Bayattork M, Minoonejad H, Andersen LL, Page P
Sci Rep 2020 Nov 26;10(1):20688. doi: 10.1038/s41598-020-77571-4. PMID: 33244045Free PMC Article

Prognosis

Zhao WH, Wang BY, Chen LJ, Fu WJ, Xu J, Liu J, Jin SW, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Zhang H, Bai J, Xu Y, Zhu H, Du J, Jiang H, Fan XH, Li JY, Hou J, Chen Z, Zhang WG, Mi JQ, Chen SJ, He AL
J Hematol Oncol 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8. PMID: 35794616Free PMC Article
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Swinney CC, Han DP, Karth PA
Ophthalmic Surg Lasers Imaging Retina 2015 Jun;46(6):650-7. doi: 10.3928/23258160-20150610-09. PMID: 26114846
Hamel CP
Orphanet J Rare Dis 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7. PMID: 17270046Free PMC Article
Singh AD, Rundle PA, Rennie I
Ophthalmol Clin North Am 2005 Mar;18(1):167-76, x. doi: 10.1016/j.ohc.2004.07.005. PMID: 15763202

Clinical prediction guides

van Tilburg SJ, Teunissen CE, Maas CCHM, Thomma RCM, Walgaard C, Heijst H, Huizinga R, van Doorn PA, Jacobs BC
EBioMedicine 2024 Apr;102:105072. Epub 2024 Mar 22 doi: 10.1016/j.ebiom.2024.105072. PMID: 38518653Free PMC Article
Shepherdson JL, Hutchison K, Don DW, McGillivray G, Choi TI, Allan CA, Amor DJ, Banka S, Basel DG, Buch LD, Carere DA, Carroll R, Clayton-Smith J, Crawford A, Dunø M, Faivre L, Gilfillan CP, Gold NB, Gripp KW, Hobson E, Holtz AM, Innes AM, Isidor B, Jackson A, Katsonis P, Amel Riazat Kesh L; Genomics England Research Consortium, Küry S, Lecoquierre F, Lockhart P, Maraval J, Matsumoto N, McCarrier J, McCarthy J, Miyake N, Moey LH, Németh AH, Østergaard E, Patel R, Pope K, Posey JE, Schnur RE, Shaw M, Stolerman E, Taylor JP, Wadman E, Wakeling E, White SM, Wong LC, Lupski JR, Lichtarge O, Corbett MA, Gecz J, Nicolet CM, Farnham PJ, Kim CH, Shinawi M
Am J Hum Genet 2024 Mar 7;111(3):487-508. Epub 2024 Feb 6 doi: 10.1016/j.ajhg.2024.01.007. PMID: 38325380Free PMC Article
Quach TT, Stratton HJ, Khanna R, Kolattukudy PE, Honnorat J, Meyer K, Duchemin AM
Acta Neuropathol 2021 Feb;141(2):139-158. Epub 2020 Nov 23 doi: 10.1007/s00401-020-02244-5. PMID: 33226471Free PMC Article
Freilinger P, Kliegel D, Hänig S, Oehl-Jaschkowitz B, Henn W, Meyer J
Am J Med Genet A 2018 Nov;176(11):2284-2291. Epub 2018 Aug 2 doi: 10.1002/ajmg.a.40477. PMID: 30070765
Toutain A, Ayrault AD, Moraine C
Am J Med Genet 1997 Aug 22;71(3):305-14. doi: 10.1002/(sici)1096-8628(19970822)71:3<305::aid-ajmg11>3.0.co;2-o. PMID: 9268101

Recent systematic reviews

Gottlieb M, Peksa GD, Carlson JN
Cochrane Database Syst Rev 2023 Nov 2;11(11):CD015089. doi: 10.1002/14651858.CD015089.pub2. PMID: 37916744Free PMC Article
Petriti U, Dudman DC, Scosyrev E, Lopez-Leon S
Syst Rev 2023 Jan 16;12(1):5. doi: 10.1186/s13643-023-02169-6. PMID: 36642718Free PMC Article
Bhandari AP, Nnate DA, Vasanthan L, Konstantinidis M, Thompson J
Cochrane Database Syst Rev 2022 Jun 6;6(6):CD003645. doi: 10.1002/14651858.CD003645.pub4. PMID: 35661343Free PMC Article
Rosa D, Terzoni S, Dellafiore F, Destrebecq A
Occup Med (Lond) 2019 Jun 24;69(4):237-243. doi: 10.1093/occmed/kqz063. PMID: 31132107
Hanchard NC, Lenza M, Handoll HH, Takwoingi Y
Cochrane Database Syst Rev 2013 Apr 30;2013(4):CD007427. doi: 10.1002/14651858.CD007427.pub2. PMID: 23633343Free PMC Article

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