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Intellectual disability, X-linked 90(XLID90)

MedGen UID:
477074
Concept ID:
C3275443
Mental or Behavioral Dysfunction
Synonyms: DLG3-Related X-Linked Nonsyndromic Mental Retardation; INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 90; XLID90
 
Gene (location): DLG3 (Xq13.1)
 
Monarch Initiative: MONDO:0010452
OMIM®: 300850

Definition

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the DLG3 gene. [from MONDO]

Clinical features

From HPO
Enuresis
MedGen UID:
8649
Concept ID:
C0014394
Disease or Syndrome
Lack of the ability to control the urinary bladder leading to involuntary urination at an age where control of the bladder should already be possible.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
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.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Professional guidelines

PubMed

Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403
Kemp S, Wanders RJ
Mol Genet Metab 2007 Mar;90(3):268-76. Epub 2006 Nov 7 doi: 10.1016/j.ymgme.2006.10.001. PMID: 17092750
Watkins PA, Naidu S, Moser HW
J Inherit Metab Dis 1987;10 Suppl 1:46-53. doi: 10.1007/BF01812846. PMID: 3119941

Recent clinical studies

Etiology

Schäfer L, Roicke H, Fischer M, Sühnel A, Köhler W
Ann Neurol 2021 Aug;90(2):266-273. Epub 2021 Jun 26 doi: 10.1002/ana.26141. PMID: 34105176
Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
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
Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C
Nature 2010 Jul 15;466(7304):368-72. Epub 2010 Jun 9 doi: 10.1038/nature09146. PMID: 20531469Free PMC Article
Nishino I
Semin Pediatr Neurol 2006 Jun;13(2):90-5. doi: 10.1016/j.spen.2006.06.004. PMID: 17027858

Diagnosis

Chaves LD, Carvalho LML, Tolezano GC, Pires SF, Costa SS, de Scliar MO, Giuliani LR, Bertola DR, Santos-Rebouças CB, Seo GH, Otto PA, Rosenberg C, Vianna-Morgante AM, Krepischi ACV
Mol Neurobiol 2023 Jul;60(7):3758-3769. Epub 2023 Mar 21 doi: 10.1007/s12035-023-03311-0. PMID: 36943625
Brambatti M, Caspi O, Maolo A, Koshi E, Greenberg B, Taylor MRG, Adler ED
Int J Cardiol 2019 Jul 1;286:92-98. Epub 2019 Feb 16 doi: 10.1016/j.ijcard.2019.01.020. PMID: 30857840
Reuter MS, Tawamie H, Buchert R, Hosny Gebril O, Froukh T, Thiel C, Uebe S, Ekici AB, Krumbiegel M, Zweier C, Hoyer J, Eberlein K, Bauer J, Scheller U, Strom TM, Hoffjan S, Abdelraouf ER, Meguid NA, Abboud A, Al Khateeb MA, Fakher M, Hamdan S, Ismael A, Muhammad S, Abdallah E, Sticht H, Wieczorek D, Reis A, Abou Jamra R
JAMA Psychiatry 2017 Mar 1;74(3):293-299. doi: 10.1001/jamapsychiatry.2016.3798. PMID: 28097321
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
Pereira PM, Schneider A, Pannetier S, Heron D, Hanauer A
Eur J Hum Genet 2010 Jun;18(6):627-33. Epub 2009 Nov 4 doi: 10.1038/ejhg.2009.189. PMID: 19888300Free PMC Article

Therapy

Chen Y, Xu LP, Zhang XH, Chen H, Liu KY, Qing J, Yang YL, Huang XJ
Pediatr Transplant 2024 May;28(3):e14735. doi: 10.1111/petr.14735. PMID: 38602169
Sestito S, Falvo F, Scozzafava C, Apa R, Pensabene L, Bonapace G, Moricca MT, Concolino D
Curr Gene Ther 2018;18(2):90-95. doi: 10.2174/1566523218666180404155759. PMID: 29618310
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NK, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W
Blood 2004 Aug 1;104(3):881-8. Epub 2004 Apr 8 doi: 10.1182/blood-2003-10-3402. PMID: 15073029
Watkins PA, Naidu S, Moser HW
J Inherit Metab Dis 1987;10 Suppl 1:46-53. doi: 10.1007/BF01812846. PMID: 3119941

Prognosis

Schäfer L, Roicke H, Fischer M, Sühnel A, Köhler W
Ann Neurol 2021 Aug;90(2):266-273. Epub 2021 Jun 26 doi: 10.1002/ana.26141. PMID: 34105176
Vianna EQ, Piergiorge RM, Gonçalves AP, Dos Santos JM, Calassara V, Rosenberg C, Krepischi ACV, Boy da Silva RT, Dos Santos SR, Ribeiro MG, Machado FB, Medina-Acosta E, Pimentel MMG, Santos-Rebouças CB
Mol Neurobiol 2020 Sep;57(9):3671-3684. Epub 2020 Jun 20 doi: 10.1007/s12035-020-01981-8. PMID: 32564284
Tarquinio DC, Hou W, Neul JL, Berkmen GK, Drummond J, Aronoff E, Harris J, Lane JB, Kaufmann WE, Motil KJ, Glaze DG, Skinner SA, Percy AK
Brain Dev 2018 Aug;40(7):515-529. Epub 2018 Apr 12 doi: 10.1016/j.braindev.2018.03.010. PMID: 29657083Free PMC Article
Polgreen LE, Chahla S, Miller W, Rothman S, Tolar J, Kivisto T, Nascene D, Orchard PJ, Petryk A
Eur J Pediatr 2011 Aug;170(8):1049-54. Epub 2011 Jan 29 doi: 10.1007/s00431-011-1401-1. PMID: 21279382Free PMC Article
Jardim LB, da Silva AC, Blank D, Villanueva MM, Renck L, Costa ML, Vargas CR, Deon M, Coelho Dl, Vedolin L, de Castro CG Jr, Gregianin L, Bonfim C, Giugliani R
Brain Dev 2010 Mar;32(3):180-90. Epub 2009 Mar 6 doi: 10.1016/j.braindev.2009.02.002. PMID: 19269120

Clinical prediction guides

Chaves LD, Carvalho LML, Tolezano GC, Pires SF, Costa SS, de Scliar MO, Giuliani LR, Bertola DR, Santos-Rebouças CB, Seo GH, Otto PA, Rosenberg C, Vianna-Morgante AM, Krepischi ACV
Mol Neurobiol 2023 Jul;60(7):3758-3769. Epub 2023 Mar 21 doi: 10.1007/s12035-023-03311-0. PMID: 36943625
Faheem M, Deneault E, Alexandrova R, Rodrigues DC, Pellecchia G, Shum C, Zarrei M, Piekna A, Wei W, Howe JL, Thiruvahindrapuram B, Lamoureux S, Ross PJ, Bradley CA, Ellis J, Scherer SW
BMC Med Genomics 2023 Jan 12;16(1):5. doi: 10.1186/s12920-022-01425-3. PMID: 36635662Free PMC Article
Schäfer L, Roicke H, Fischer M, Sühnel A, Köhler W
Ann Neurol 2021 Aug;90(2):266-273. Epub 2021 Jun 26 doi: 10.1002/ana.26141. PMID: 34105176
Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
Fieremans N, Van Esch H, Holvoet M, Van Goethem G, Devriendt K, Rosello M, Mayo S, Martinez F, Jhangiani S, Muzny DM, Gibbs RA, Lupski JR, Vermeesch JR, Marynen P, Froyen G
Hum Mutat 2016 Aug;37(8):804-11. Epub 2016 May 25 doi: 10.1002/humu.23012. PMID: 27159028Free PMC Article

Recent systematic reviews

Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403

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