INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED ... - OMIM

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#300966 Table of Contents

  • Title
  • Phenotype-Gene Relationships
  • Clinical Synopsis
  • Phenotypic Series
  • Text
  • Description
  • Clinical Features
  • Cytogenetics
  • Molecular Genetics
  • Animal Model
  • References
  • Creation Date
  • Edit History

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▼ Clinical Resources Clinical Trials EuroGentest GTR OrphaNet ICD+ # 300966

INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 33; MRXS33

Alternative titles; symbols

MENTAL RETARDATION, X-LINKED, SYNDROMIC 33

Phenotype-Gene Relationships

Location Phenotype Phenotype MIM number Inheritance Phenotype mapping key Gene/Locus Gene/Locus MIM number
Xq13.1 Intellectual developmental disorder, X-linked syndromic 33 300966 XLR 3 TAF1 313650
Clinical Synopsis Toggle Dropdown Phenotypic Series Toggle Dropdown PheneGene Graphics
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INHERITANCE - X-linked recessive [UMLS: C1279481, C1845977 HPO: HP:0001419] [HPO: HP:0001419] GROWTH Other - Intrauterine growth retardation [SNOMEDCT: 22033007] [ICD9CM: 764.9, 764.90] [UMLS: C0015934 HPO: HP:0001511] [HPO: HP:0001511] - Growth retardation, postnatal [UMLS: C1859778 HPO: HP:0008897] [SNOMEDCT: 59576002, 444896005] [HPO: HP:0001510] HEAD & NECK Head - Microcephaly [SNOMEDCT: 1148757008] [ICD10CM: Q02] [ICD9CM: 742.1] [UMLS: C0025958, C4551563 HPO: HP:0000252] [HPO: HP:0000252] Face - Long face [UMLS: C1836047 HPO: HP:0000276] [HPO: HP:0000276] - Long philtrum [SNOMEDCT: 1145317008] [UMLS: C1865014 HPO: HP:0000343] [HPO: HP:0000343] - Sagging cheeks [UMLS: C2673771] - Pointed chin [UMLS: C1844505 HPO: HP:0000307] [HPO: HP:0000307] Ears - Low-set ears [SNOMEDCT: 95515009] [ICD10CM: Q17.4] [UMLS: C0239234 HPO: HP:0000369] [HPO: HP:0000369] - Protruding ears [UMLS: C1855285 HPO: HP:0000411] [HPO: HP:0000411] - Chronic otitis media [SNOMEDCT: 21186006] [ICD10CM: H66.9] [UMLS: C0271441 HPO: HP:0000389] [HPO: HP:0000389] - Hearing impairment (in some patients) [SNOMEDCT: 103276001, 15188001] [ICD10CM: H91.9] [ICD9CM: 389, 389.9] [UMLS: C1384666, C1550444 HPO: HP:0000365] [HPO: HP:0000365] Eyes - Prominent supraorbital ridges [UMLS: C1842060 HPO: HP:0000336] [HPO: HP:0000336] - Downslanting palpebral fissures [SNOMEDCT: 246800008] [UMLS: C0423110 HPO: HP:0000494] [HPO: HP:0000494] - Strabismus [SNOMEDCT: 22066006] [ICD10CM: H50.9, H50.40] [UMLS: C0038379, C1423541, C2020541 HPO: HP:0000486] [HPO: HP:0000486] Nose - Anteverted nares [SNOMEDCT: 708670007] [UMLS: C1840077 HPO: HP:0000463] [HPO: HP:0000463] Mouth - High-arched palate [SNOMEDCT: 27272007, 1144376004] [ICD10CM: Q38.5] [UMLS: C0240635, C5980175 HPO: HP:0000218] [HPO: HP:0000218] ABDOMEN Gastrointestinal - Oropharyngeal dysphagia [SNOMEDCT: 71457002] [ICD10CM: R13.12] [ICD9CM: 787.22] [UMLS: C0267071 HPO: HP:0200136] [HPO: HP:0200136] SKELETAL - Joint hypermotility [UMLS: C4230840] Spine - Gluteal crease with sacral caudal remnant [UMLS: C4230839] - Sacral dimple [SNOMEDCT: 311897005] [ICD10CM: L05.91] [UMLS: C0426848 HPO: HP:0000960] [HPO: HP:0000960] - Prominent protruding coccyx [UMLS: C1850044 HPO: HP:0008472] [HPO: HP:0008472] SKIN, NAILS, & HAIR Skin - Sacral dimple [SNOMEDCT: 311897005] [ICD10CM: L05.91] [UMLS: C0426848 HPO: HP:0000960] [HPO: HP:0000960] MUSCLE, SOFT TISSUES - Hypotonia [SNOMEDCT: 398152000, 398151007] [UMLS: C1858120, C0026827 HPO: HP:0001252, HP:0001290] [HPO: HP:0001252] NEUROLOGIC Central Nervous System - Delayed psychomotor development [SNOMEDCT: 224958001] [ICD10CM: F88] [UMLS: C0557874 HPO: HP:0001263] [HPO: HP:0001263] - Intellectual disability [SNOMEDCT: 110359009, 228156007] [ICD9CM: 317-319.99] [UMLS: C3714756 HPO: HP:0001249] [HPO: HP:0001249] - Delayed speech [SNOMEDCT: 229721007] [UMLS: C0241210 HPO: HP:0000750] [HPO: HP:0000750] - Spastic diplegia (in some patients) [SNOMEDCT: 281411007] [ICD10CM: G80.1] [UMLS: C0023882 HPO: HP:0001264] [HPO: HP:0001264] - Tremor (in some patients) [SNOMEDCT: 26079004] [ICD10CM: R25.1] [UMLS: C0040822 HPO: HP:0001337] [HPO: HP:0001337] - Dystonic movements (in some patients) [UMLS: C0013421 HPO: HP:0001332] [HPO: HP:0001332] - Hypoplasia of the corpus callosum (in some patients) [SNOMEDCT: 204043002] [UMLS: C0344482 HPO: HP:0002079] [HPO: HP:0002079] - Enlarged ventricles (in some patients) [UMLS: C3278923 HPO: HP:0002119] [HPO: HP:0002119] - Cerebellar hypoplasia (in some patients) [SNOMEDCT: 16026008] [UMLS: C0266470 HPO: HP:0001321] [HPO: HP:0001321] Behavioral Psychiatric Manifestations - Autistic features [UMLS: C1846135] [HPO: HP:0000729] MISCELLANEOUS - Onset at birth [UMLS: C1836142 HPO: HP:0003577] [HPO: HP:0003577] - De novo mutation in most patients MOLECULAR BASIS - Caused by mutation in the TATA box-binding protein-associated factor-1 gene (TAF1, 313650.0002) ▲ Close

Intellectual developmental disorder, X-linked syndromic - PS309510 - 54 Entries
Location Phenotype Inheritance Phenotypemapping key PhenotypeMIM number Gene/Locus Gene/LocusMIM number
Xp22.2 Raynaud-Claes syndrome XLD 3 300114 CLCN4 302910
Xp22.2 Basilicata-Akhtar syndrome XLD 3 301032 MSL3 300609
Xp22.2 Intellectual developmental disorder, X-linked syndromic, Pilorge type XL 3 301076 GLRA2 305990
Xp22.2 Pettigrew syndrome XLR 3 304340 AP1S2 300629
Xp22.12 Intellectual developmental disorder, X-linked syndromic, Houge type XL 3 301008 CNKSR2 300724
Xp22.11 Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type XLR 3 309583 SMS 300105
Xp22.11 MEHMO syndrome XLR 3 300148 EIF2S3 300161
Xp22.11 Intellectual developmental disorder, X-linked syndromic 37 XL 3 301118 ZFX 314980
Xp22.11-p21.3 Van Esch-O'Driscoll syndrome XLR 3 301030 POLA1 312040
Xp21.3 Partington syndrome XLR 3 309510 ARX 300382
Xp21.1-p11.23 Intellectual developmental disorder, X-linked syndromic 17 XLR 2 300858 MRXS17 300858
Xp11 ?Intellectual developmental disorder, X-linked syndromic 12 XL 2 309545 MRXS12 309545
Xp11.4 Intellectual developmental disorder, X-linked syndromic, Hedera type XLR 3 300423 ATP6AP2 300556
Xp11.4 Intellectual developmental disorder, X-linked syndromic, Snijders Blok type XLD, XLR 3 300958 DDX3X 300160
Xp11.4 Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia XL 3 300749 CASK 300172
Xp11.3-q22 Intellectual developmental disorder, X-linked syndromic 7 XL 2 300218 MRXS7 300218
Xp11.2 Intellectual developmental disorder, X-linked, syndromic, Stocco dos Santos type XL 2 300434 SDSX 300434
Xp11.23 Renpenning syndrome XLR 3 309500 PQBP1 300463
Xp11.22 Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type XLR 3 300534 KDM5C 314690
Xp11.22 Intellectual developmental disorder, X-linked syndromic, Turner type XL 3 309590 HUWE1 300697
Xp11.22 Intellectual developmental disorder, X-linked syndromic, Siderius type XLR 3 300263 PHF8 300560
Xp11.22 Prieto syndrome XLR 3 309610 WNK3 300358
Xq11.2 Wieacker-Wolff syndrome XLR 3 314580 ZC4H2 300897
Xq12-q21.31 Intellectual developmental disorder, X-linked syndromic 9 2 300709 MRXS9 300709
Xq12 Wilson-Turner syndrome XLR 3 309585 LAS1L 300964
Xq12 Intellectual developmental disorder, X-linked syndromic, Billuart type XLR 3 300486 OPHN1 300127
Xq13-q21 Martin-Probst syndrome XLR 2 300519 MRXSMP 300519
Xq13.1 ?Corpus callosum, agenesis of, with impaired intellectual development, ocular coloboma and micrognathia XLR 3 300472 IGBP1 300139
Xq13.1 Lujan-Fryns syndrome XLR 3 309520 MED12 300188
Xq13.1 Intellectual developmental disorder, X-linked syndromic 34 XL 3 300967 NONO 300084
Xq13.1 Intellectual developmental disorder, X-linked syndromic 33 XLR 3 300966 TAF1 313650
Xq13.2 Intellectual developmental disorder, X-linked syndromic, Abidi type XL 2 300262 MRXSAB 300262
Xq13.2 Tonne-Kalscheuer syndrome XL 3 300978 RLIM 300379
Xq21.33-q23 Intellectual developmental disorder, X-linked syndromic, Chudley-Schwartz type XLR 2 300861 MRXSCS 300861
Xq22.1 Intellectual developmental disorder, X-linked syndromic, Bain type XLD 3 300986 HNRNPH2 300610
Xq22.3 Arts syndrome XLR 3 301835 PRPS1 311850
Xq24 Intellectual developmental disorder, X-linked syndromic, Nascimento type XLR 3 300860 UBE2A 312180
Xq24 Intellectual developmental disorder, X-linked syndromic 14 XLR 3 300676 UPF3B 300298
Xq24 Intellectual developmental disorder, X-linked syndromic, Hackman-Di Donato type XLR 3 301039 NKAP 300766
Xq24 Intellectual developmental disorder, X-linked syndromic, Cabezas type XLR 3 300354 CUL4B 300304
Xq25 Intellectual developmental disorder, X-linked syndromic, Wu type XLR 3 300699 GRIA3 305915
Xq26.1 Intellectual developmental disorder, X-linked syndromic, Raymond type XL 3 300799 ZDHHC9 300646
Xq26.2 ?Paganini-Miozzo syndrome XLR 3 301025 HS6ST2 300545
Xq26.2 Borjeson-Forssman-Lehmann syndrome XLR 3 301900 PHF6 300414
Xq26.3 Intellectual developmental disorder, X-linked syndromic, Christianson type XL 3 300243 SLC9A6 300231
Xq26.3 ?Intellectual developmental disorder, X-linked syndromic, Shashi type XLR 3 300238 RBMX 300199
Xq26.3 ?Intellectual developmental disorder, X-linked syndromic, Gustavson type XLR 3 309555 RBMX 300199
Xq27.3 Fragile X syndrome XLD 3 300624 FMR1 309550
Xq28 Intellectual developmental disorder, X-linked 109 XLR 3 309548 AFF2 300806
Xq28 Intellectual developmental disorder, X-linked syndromic 13 XLR 3 300055 MECP2 300005
Xq28 Intellectual developmental disorder, X-linked syndromic, Lubs type XLR 3 300260 MECP2 300005
Xq28 Intellectual developmental disorder, X-linked syndromic 35 XLR 3 300998 RPL10 312173
Xq28 Intellectual developmental disorder, X-linked syndromic, Armfield type XLR 3 300261 FAM50A 300453
Chr.X Intellectual developmental disorder, X-linked, syndromic 32 XLR 2 300886 MRXS32 300886
▲ Close

TEXT

A number sign (#) is used with this entry because of evidence that X-linked syndromic intellectual developmental disorder-33 (MRXS33) is caused by mutation in the TAF1 gene (313650) on chromosome Xq13.

Description

X-linked syndromic intellectual developmental disorder-33 (MRXS33) is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).

Clinical Features

O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with a complex X-linked neurodevelopmental syndrome. The boys had global developmental delay, intellectual disability with delayed speech and language, generalized hypotonia, and joint hypermobility. Most had intrauterine and/or postnatal growth retardation and oropharyngeal dysphagia. Common facial dysmorphic features included prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, sagging cheeks, long philtrum, low-set and protruding ears, long face, high-arched palate, thin upper lip, pointed chin, and broad upturned nose with bulbous nasal tip. Other widely shared features included hearing impairment, microcephaly, and hypoplasia of the corpus callosum. Some additional neurologic features included spastic diplegia, dystonic movements, and tremors. Three patients from 1 family had seizures soon after birth, but other patients did not have seizures. Some had autistic behaviors. All patients also had a characteristic gluteal crease with a sacral caudal remnant, although spine imaging on 2 patients did not show any major underlying defect. Extensive clinical information was available in the supplemental material.

Cytogenetics

O'Rawe et al. (2015) reported 2 unrelated boys with delayed psychomotor development, intellectual disability, dysmorphic facial features, and severe neurodegenerative phenotype associated with small duplications (0.423 Mb and 0.42 Mb, respectively) of chromosome Xq13 encompassing the TAF1 gene and other genes. One of the deletions was inherited from an unaffected mother who showed skewed X-inactivation; this patient also had a deletion at chromosome 17q21. The deletion in the other patient occurred de novo.

Molecular Genetics

In 12 boys from 9 unrelated families with MRXS33, O'Rawe et al. (2015) identified 9 different hemizygous mutations in the TAF1 gene (see, e.g., 313650.0002-313650.0006). Most of the mutations occurred de novo, although 3 were inherited from an unaffected mother, 1 of whom showed skewed X-inactivation. Functional studies were not performed, but many of the variants affected highly conserved residues in domains critical for interaction with TAF7 (600573) and were predicted to disrupt this interaction. Gene expression studies in 1 family with a missense mutation (I1337T; 313650.0002) suggested that the phenotype is associated with downregulation of a set of genes regulated by E-box proteins. The mutations were found by several strategies, including whole-genome sequencing, exome sequencing, targeted gene-panel sequencing, and microarray-based strategies, and all were confirmed by Sanger sequencing.

Animal Model

O'Rawe et al. (2015) found that knockdown of the taf1 gene in zebrafish resulted in a 10% reduction in the relative area of the optic tectum, suggesting a neuronal defect.

REFERENCES

  1. O'Rawe, J. A., Wu, Y., Dorfel, M. J., Rope, A. F., Au, P. Y. B., Parboosingh, J. S., Moon, S., Kousi, M., Kosma, K., Smith, C. S., Tzetis, M., Schuette, J. L., and 36 others. TAF1 variants are associated with dysmorphic features, intellectual disability, and neurological manifestations. Am. J. Hum. Genet. 97: 922-932, 2015. [PubMed: 26637982, images, related citations] [Full Text]

Creation Date: Cassandra L. Kniffin : 12/28/2015 Edit History: alopez : 08/20/2021 carol : 01/11/2016ckniffin : 1/8/2016

# 300966

INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 33; MRXS33

Alternative titles; symbols

MENTAL RETARDATION, X-LINKED, SYNDROMIC 33

SNOMEDCT: 1237420004; ORPHA: 480907; MONDO: 0010500;

Phenotype-Gene Relationships

Location Phenotype Phenotype MIM number Inheritance Phenotype mapping key Gene/Locus Gene/Locus MIM number
Xq13.1 Intellectual developmental disorder, X-linked syndromic 33 300966 X-linked recessive 3 TAF1 313650

TEXT

A number sign (#) is used with this entry because of evidence that X-linked syndromic intellectual developmental disorder-33 (MRXS33) is caused by mutation in the TAF1 gene (313650) on chromosome Xq13.

Description

X-linked syndromic intellectual developmental disorder-33 (MRXS33) is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).

Clinical Features

O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with a complex X-linked neurodevelopmental syndrome. The boys had global developmental delay, intellectual disability with delayed speech and language, generalized hypotonia, and joint hypermobility. Most had intrauterine and/or postnatal growth retardation and oropharyngeal dysphagia. Common facial dysmorphic features included prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, sagging cheeks, long philtrum, low-set and protruding ears, long face, high-arched palate, thin upper lip, pointed chin, and broad upturned nose with bulbous nasal tip. Other widely shared features included hearing impairment, microcephaly, and hypoplasia of the corpus callosum. Some additional neurologic features included spastic diplegia, dystonic movements, and tremors. Three patients from 1 family had seizures soon after birth, but other patients did not have seizures. Some had autistic behaviors. All patients also had a characteristic gluteal crease with a sacral caudal remnant, although spine imaging on 2 patients did not show any major underlying defect. Extensive clinical information was available in the supplemental material.

Cytogenetics

O'Rawe et al. (2015) reported 2 unrelated boys with delayed psychomotor development, intellectual disability, dysmorphic facial features, and severe neurodegenerative phenotype associated with small duplications (0.423 Mb and 0.42 Mb, respectively) of chromosome Xq13 encompassing the TAF1 gene and other genes. One of the deletions was inherited from an unaffected mother who showed skewed X-inactivation; this patient also had a deletion at chromosome 17q21. The deletion in the other patient occurred de novo.

Molecular Genetics

In 12 boys from 9 unrelated families with MRXS33, O'Rawe et al. (2015) identified 9 different hemizygous mutations in the TAF1 gene (see, e.g., 313650.0002-313650.0006). Most of the mutations occurred de novo, although 3 were inherited from an unaffected mother, 1 of whom showed skewed X-inactivation. Functional studies were not performed, but many of the variants affected highly conserved residues in domains critical for interaction with TAF7 (600573) and were predicted to disrupt this interaction. Gene expression studies in 1 family with a missense mutation (I1337T; 313650.0002) suggested that the phenotype is associated with downregulation of a set of genes regulated by E-box proteins. The mutations were found by several strategies, including whole-genome sequencing, exome sequencing, targeted gene-panel sequencing, and microarray-based strategies, and all were confirmed by Sanger sequencing.

Animal Model

O'Rawe et al. (2015) found that knockdown of the taf1 gene in zebrafish resulted in a 10% reduction in the relative area of the optic tectum, suggesting a neuronal defect.

REFERENCES

  1. O'Rawe, J. A., Wu, Y., Dorfel, M. J., Rope, A. F., Au, P. Y. B., Parboosingh, J. S., Moon, S., Kousi, M., Kosma, K., Smith, C. S., Tzetis, M., Schuette, J. L., and 36 others. TAF1 variants are associated with dysmorphic features, intellectual disability, and neurological manifestations. Am. J. Hum. Genet. 97: 922-932, 2015. [PubMed: 26637982] [Full Text: https://doi.org/10.1016/j.ajhg.2015.11.005]

Creation Date: Cassandra L. Kniffin : 12/28/2015 Edit History: alopez : 08/20/2021carol : 01/11/2016ckniffin : 1/8/2016

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions. OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University. Copyright® 1966-2026 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions. OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University. Copyright® 1966-2026 Johns Hopkins University. Printed: Jan. 2, 2026

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