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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)