Non-syndromic X-linked intellectual disability(XLID)

MedGen UID:: 502019
•Concept ID:: C3501611
•: Disease or Syndrome

Synonyms:	Mental retardation, nonsyndromic, X-linked; XLID
Modes of inheritance:	X-linked recessive inheritance MedGen UID: 375779 •Concept ID: C1845977 • Finding Source: Orphanet A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. See: This record X-linked recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	NEXMIF (Xq13.3)

Monarch Initiative:	MONDO:0019181
OMIM® Phenotypic series:	PS309530
Orphanet:	ORPHA777

Definition

Nonspecific X-linked intellectual deficiencies (MRX) belong to the family of sex-linked intellectual deficiencies (XLMR). In contrast to syndromic or specific X-linked intellectual deficiencies (MRXS), which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only symptom of MRX. [from MONDO]

Professional guidelines

PubMed

Which types of conditions should be included in reproductive genetic carrier screening? Views of parents of children with a genetic condition.

Thomas LA, Lewis S, Massie J, Kirk EP, Archibald AD, Barlow-Stewart K, Boardman FK, Halliday J, McClaren B, Delatycki MB
Eur J Med Genet 2020 Dec;63(12):104075. Epub 2020 Sep 30 doi: 10.1016/j.ejmg.2020.104075. PMID: 33007447

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

Grams SE, Argiropoulos B, Lines M, Chakraborty P, Mcgowan-Jordan J, Geraghty MT, Tsang M, Eswara M, Tezcan K, Adams KL, Linck L, Himes P, Kostiner D, Zand DJ, Stalker H, Driscoll DJ, Huang T, Rosenfeld JA, Li X, Chen E
Am J Med Genet A 2016 Apr;170A(4):967-77. Epub 2015 Dec 22 doi: 10.1002/ajmg.a.37519. PMID: 26692240

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Recent clinical studies

Etiology

KDM5C mutational screening among males with intellectual disability suggestive of X-Linked inheritance and review of the literature.

Gonçalves TF, Gonçalves AP, Fintelman Rodrigues N, dos Santos JM, Pimentel MM, Santos-Rebouças CB
Eur J Med Genet 2014 Mar;57(4):138-44. Epub 2014 Feb 27 doi: 10.1016/j.ejmg.2014.02.011. PMID: 24583395

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Diagnosis

Clinical and Molecular Aspects of the Neurodevelopmental Disorder Associated with PAK3 Perturbation.

Pascolini G, Gaudioso F, Passarelli C, Novelli A, Di Giosaffatte N, Majore S, Grammatico P
J Mol Neurosci 2021 Dec;71(12):2474-2481. Epub 2021 Jul 5 doi: 10.1007/s12031-021-01868-w. PMID: 34227036

KIAA2022 nonsense mutation in a symptomatic female.

Farach LS, Northrup H
Am J Med Genet A 2016 Mar;170(3):703-6. Epub 2015 Nov 17 doi: 10.1002/ajmg.a.37479. PMID: 26576034

KDM5C mutational screening among males with intellectual disability suggestive of X-Linked inheritance and review of the literature.

Xq22.3-q23 deletion including ACSL4 in a patient with intellectual disability.

Gazou A, Riess A, Grasshoff U, Schäferhoff K, Bonin M, Jauch A, Riess O, Tzschach A
Am J Med Genet A 2013 Apr;161A(4):860-4. Epub 2013 Mar 12 doi: 10.1002/ajmg.a.35778. PMID: 23520119

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Therapy

Skewed X-inactivation in a family with DLG3-associated X-linked intellectual disability.

Gieldon L, Mackenroth L, Betcheva-Krajcir E, Rump A, Beck-Wödl S, Schallner J, Di Donato N, Schröck E, Tzschach A
Am J Med Genet A 2017 Sep;173(9):2545-2550. Epub 2017 Aug 4 doi: 10.1002/ajmg.a.38348. PMID: 28777483

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Prognosis

A mutation in PAK3 with a dual molecular effect deregulates the RAS/MAPK pathway and drives an X-linked syndromic phenotype.

Magini P, Pippucci T, Tsai IC, Coppola S, Stellacci E, Bartoletti-Stella A, Turchetti D, Graziano C, Cenacchi G, Neri I, Cordelli DM, Marchiani V, Bergamaschi R, Gasparre G, Neri G, Mazzanti L, Patrizi A, Franzoni E, Romeo G, Bordo D, Tartaglia M, Katsanis N, Seri M
Hum Mol Genet 2014 Jul 1;23(13):3607-17. Epub 2014 Feb 19 doi: 10.1093/hmg/ddu070. PMID: 24556213

Deletion of the immunoglobulin domain of IL1RAPL1 results in nonsyndromic X-linked intellectual disability associated with behavioral problems and mild dysmorphism.

Franek KJ, Butler J, Johnson J, Simensen R, Friez MJ, Bartel F, Moss T, DuPont B, Berry K, Bauman M, Skinner C, Stevenson RE, Schwartz CE
Am J Med Genet A 2011 May;155A(5):1109-14. Epub 2011 Apr 11 doi: 10.1002/ajmg.a.33833. PMID: 21484992

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