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Table 1 List of intellectual disabilities highly comorbid with autism, including gene symbols, SFARI ratings, estimates of autism comorbidity, and indications of epilepsy comorbidity

From: Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression

Intellectual disability (OMIM #) Gene symbol SFARI rating Autism comorbidity References Epilepsy frequency
Adenylosuccinase Deficiency (#103050) ADSL S 38 % (N = 8) Jaeken et al. 1988 [36] Common
Alpha-thalassemia/Mental Retardation Syndrome (#301040) ATRX 6 27 %, males (N = 73) Wada and Gibbons 2003 [37] Common
Angelman Syndrome (#105830) UBE3A S 79 % (N = 39) Bonati et al. 2007 [38] Common
Trillingsgaard and Østergaard 2004 [39]
Autosomal Dominant Mental Retardation 1 (#156200) MBD5 3S 100 % (N = 14) Talkowski et al. 2011 [40] Common
Autosomal Dominant Mental Retardation 5 (#612621) SYNGAP1 1S 60 % (N = 10) Hamdan et al. 2011 [41] Common
Carvill et al. 2013 [42]
Berryer et al. 2013 [43]
Autosomal Dominant Mental Retardation 12 (#614562) ARID1B S 63 % (N = 8) Halgren et al. 2012 [44] Variable
Autosomal Dominant Mental Retardation 23 (#615761) SETD5 1S ≤71 % (N = 7) Grozeva et al. 2014 [45] No evidence
Autosomal Dominant Mental Retardation 24 (#615828) DEAF1 2S 75 % (N = 4) Vulto-van Silfhout et al. 2014 [46] No evidence
Autosomal Dominant Mental Retardation 26 (#615834) AUTS2 3 41 % (N = 17) Beunders et al. 2013 [47] Variable
Autosomal Dominant Mental Retardation 30 (#616083) ZMYND11 3 29 % (N = 7) Coe et al. 2014 [48] Variable
Autosomal Recessive Mental Retardation 3 (#608443) CC2D1A 3 31 % (N = 16) Manzini et al. 2014 [49] Variable
Autosomal Recessive Mental Retardation 38 (#615516) HERC2 NS 86 % (N = 7) Puffenberger et al. 2012 [50] Common
Athabaskan Brainstem Dysgenesis Syndrome (#601536) HOXA1 S 22 % (N = 9) Tischfield et al. 2005 [51] Variable
Branched-chain Ketoacid Dehydrogenase Kinase Deficiency (#614923) BCKDK 3 100 % (N = 6) Novarino et al. 2012 [52] Variable
Brunner Syndrome (#300615) MAOA 4 71 %, males (N = 7) Piton et al. 2014 [53] Uncommon
Palmer et al. 2016 [54]
Cardiofaciocutaneous Syndrome 1 (#115150) BRAF NS 20 % (N = 15) Nava et al. 2007 [55] Common
Cardiofaciocutaneous Syndrome 3 (#615279) MAP2K1 NI 63 % (N = 8) Nava et al. 2007 [55] Common
Cerebral Creatine Deficiency Syndrome 1 (#300352) SLC6A8 4 68 % (N = 28) Dunbar et al. 2014 [56] Common
Cerebral Creatine Deficiency Syndrome 2 (#612736) GAMT NI 43 % (N = 7) Cheillan et al. 2012 [57] Common
Cerebral Creatine Deficiency Syndrome 3 (#612718) GATM NS 35 % (N = 20) Mercimek-Mahmutoglu et al. 2014 [58] Variable
CHARGE Syndrome (#214800) CHD7 S 60 % (N = 10) Smith et al. 2005 [59] Variable
Childhood-onset Epileptic Encephalopathy (#615369) CHD2 2S 50 % (N = 6) Chénier et al. 2014 [60] Common
Christian-type of X-linked Syndromic Mental Retardation (#300243) SLC9A6 S 89 %, males (N = 9) Pescosolido et al. 2014 [61] Common
Chromosome 2p16.3 Deletion Syndrome (#614332) NRXN1 2 50 % (N = 40) Dabell et al. 2013 [62] Variable
Schaaf et al. 2012 [63]
Cohen Syndrome (#216550) VPS13B S 49 % (N = 45) Howlin et al. 2005 [64] Common
Congenital Rett Syndrome (#613454) FOXG1 5 100 % (N = 26) Kortüm et al. 2011 [65] Common
Cornelia de Lange Syndrome 1-5 (#122470, 300590, 610759, 614701, 300882) NIPBL NI 62 % (N = 34) Moss et al. 2008 [66] Variable
SMC1A
SMC3
RAD21
HDAC8
Early Infantile Epileptic Encephalopathy 4 (#612164) STXBP1 NS 29 % (N = 7) Barcia et al. 2014 [67] Common
Early Infantile Epileptic Encephalopathy 6 (#607208) SCN1A S 24 % (N = 37) Li et al. 2011 [68] Common
Early Infantile Epileptic Encephalopathy 9 (#300088) PCDH19 S 22 %, females (N = 27) Scheffer et al. 2008 [69] Common
Early Infantile Epileptic Encephalopathy 24 (#615871) HCN1 NS 66 % (N = 6) Nava et al. 2014 [70] Common
Fragile X Mental Retardation Syndrome (#300624) FMR1 S 45 % (N = 64) Clifford et al. 2007 [71] Common
Glass Syndrome (#612313) SATB2 4 29 % (N = 7) Balasubramanian et al. 2011 [72] Common
Helsmoortel-Van der AA Syndrome (#615873) ADNP 1 100 % (N = 11) Helsmoortel et al. 2014 [73] Common
Pescosolido et al. 2014 [61]
KBG Syndrome (#148050) ANKRD11   33 % (N = 9) Ockeloen et al. 2014 [74] Uncommon
Kleefstra Syndrome (#610253) EHMT1 3S most, % unknown (N = 20) Willemsen et al. 2012 [75] Common
Lowe Oculocerebrorenal Syndrome (#309000) OCRL NS 71 %, males (N = 52) Oliver et al. 2011 [76] Common
Lubs X-linked Mental Retardation Syndrome (#300260) MECP2 S 100 %, males (N = 18) Ramocki et al. 2009 [77] Common
Lujan-Fryns Syndrome (#309520) MED12 6 ≤62 %, males (N = 32) Williams 2006 [78] Common
Marshall-Smith Syndrome (#602535) NFIX NI 83 % (N = 6) van Balkom et al. 2011 [79] Variable
Mental Retardation with Language Impairment and Autistic Features (#613670) FOXP1 3 75 % (N = 4) Le Fevre et al. 2013 [80] Variable
Mowat-Wilson Syndrome (#235730) ZEB2 NI 40 % (N = 6) Evans et al. 2012 [81] Common
Mucopolysaccharidosis, Type IIIA (#252900) SGSH NI 29 % (N = 73) Héron et al. 2011 [82] Common
Muscular Dystrophy-dystroglycanopathy (Congenital with Mental Retardation), Type B3 (#613151) POMGNT1 NS 22 % (N = 9) Hehr et al. 2007 [83] Variable
Myhre Syndrome (#139210) SMAD4 NS 25 % (N = 8) Caputo et al. 2012 [84] Variable
Myotonic Dystrophy 1 (#160900) DMPK S 49 % (N = 57) Ekström et al. 2008 [85] Variable
Neurodegeneration due to Cerebral Folate Transport Deficiency (#613068) FOLR1 NI 35 % (N = 20) Ramaekers and Blau 2004 [86] Common
Steinfeld et al. 2009 [87]
Nicolaides-Baraitser Syndrome (#601358) SMARCA2 NI 28 % (N = 18) Sousa et al. 2009 [88] Common
Noonan Syndrome 3 (#609942) KRAS NI 33 % (N = 6) Nava et al. 2007 [55] Uncommon
Nonphotosensitive Trichothiodystrophy 1 (#234050) MPLKIP NI 60 % (N = 5) Heller et al. 2015 [89] Variable
Noonan Syndrome 3 (#609942) KRAS NI 33 % (N = 6) Nava et al. 2007 [55] Variable
Norrie Disease (#310600) NDP NI 27 %, males (N = 56) Smith et al. 2012 [90] Uncommon
Phelan-McDermid Syndrome (#606232) SHANK3 1S 52 % (N = 130) Phelan et al. 2001 [91] Common
Cusmano-Ozog et al. 2007 [92]
Dhar et al. 2010 [93]
Pitt-Hopkins Syndrome (#610954) TCF4 NS 75 % (N = 8) van Balkom et al. 2011 [79] Vommon
Renpenning Syndrome 1 (#309500) PQBP1 NI 38 %, males (N = 13) Germanaud et al. 2011 [94] Variable
Rett Syndrome (#312750) MECP2 S 100 %, females (N = 35) Hagberg et al. 1983 [95] Common
Schaaf-Yang Syndrome (#615547) MAGEL2 NS 100 % (N = 6) Schaaf et al. 2013 [96] Common
Soden et al. 2014 [97]
Smith-Lemli-Opitz Syndrome (#270400) DHCR7 S 75 % (N = 14) Sikora et al. 2006 [98] Common
Smith-Magenis Syndrome (#182290) RAI1 S 90 % (N = 26) Laje et al. 2010 [99] Common
Temtamy Syndrome (#218340) C12orf57 NS 100 % (N = 10) Akizu et al. 2013 [100] Common
Tuberous Sclerosis 2 (#613254) TSC2 S 40 % (N = 103) Numis et al. 2011 [101] Common
Warburg Micro Syndrome 4 (#615663) TBC1D20 NI 100 % (N = 7) Liegel et al. 2013 [102] Common
Wiedemann-Steiner Syndrome (#605130) KMT2A 2S 33 % (N = 6) Jones et al. 2012 [103] Variable
Wu Type of X-linked Syndromic Mental Retardation (#300699) GRIA3 NI 32 %, males (N = 6) Philips et al. 2014 [104] Common
X-linked Mental Retardation 1 (#309530) IQSEC2 NI 55 %, males (N = 9) Tran Mau-Them et al. 2013 [105] Uncommon
Shoubridge et al. 2010 [106]
X-linked Mental Retardation 72 (#300271) RAB39B 4 33 %, males (N = 9) Russo et al. 2000 [107] Common
Giannandrea et al. 2010 [108]
X-linked Mental Retardation 98 (#300912) KIAA2022 NS 43 %, males (N = 7) van Maldergem et al. 2013 [109] Common
X-linked Mental Retardation with or without Seizures (#300419) ARX S 50 %, males (N = 6) Turner et al. 2002 [110] Variable
X-linked Syndromic Mental Retardation 14 (#300676) UPF3B S 50 %, males (N = 8) Tarpey et al. 2007 [111] Variable
  1. Thirty-two of these genes are either not included in the SFARI Gene Database, are unscored, or are scored as a “6”. SFARI rating system: S = syndromic; 1 = high confidence; 2 = strong evidence; 3 = suggestive evidence; 4 = minimal evidence; 5 = hypothesized; 6 = not supported; NI = not included, NS = included but not scored (see Additional file 2 for references used to estimate comorbidities)