Table 1

Clinical and imaging features of patients with variants in TUBB2A

Patient123456789101112
SexMMFMFMMFFFMM
Nucleotide sequence variationc.145G>Ac.1186C>Tc.146T>Gc.267C>Ac.5G>Ac.1070C>Tc.1070C>Tc.743C>Tc.743C>Tc.1228G>Ac.689C>Tc.743C>T
Protein sequence variationp.(Val49Met)p.(His396Tyr)p.(Val49Gly)p.(Asn89Lys)p.(Arg2His)p.(Pro357Leu)p.(Pro357Leu)p.(Ala248Val)p.(Ala248Val)p.(Glu410Lys)p.(Ser230Leu)p.(Ala248Val)
InheritanceDe novoDe novoDe novoDe novoDe novoDe novoDe novoDe novoDe novoDe novoDe novoDe novo
Age at examination5 years7 years2 years 6 months6 years 8 months2 years 8 months15 years11 years8 years 2 months3 years4 years 2 months32 years4 years 8 months
MircocephalyNoYesYesNoYesYesNon/an/aNoNoYes
Dysmorphic featuresYesn/aNoFacial dysmorphisms, abnormal dermatoglyphsFacial dysmorphisms, clinodactyly of toesMild dysmorphismsNoNon/aEpicanthusFacial asymmetryNo
IDYesYesYesYesYesYesYesYesYesYesYesYes
Motor impairmentAmbulant>2 yearsNon-ambulatoryNon-ambulatoryBroad-based gait, stereotypesAmbulant at 26 months, broad-based gaitSevere impairmentNon-ambualtory, GMFCS5Walks with supportAmbulated at 38 monthsNoAmbulated at 2 yearsAmbulated at 25 months
SpeechNon-verbalNon-verbalNon-verbalNon-verbalSingle wordsNon-verbalNon-verbalNon-verbalNon-verbalDelayed and impairedDelayed and impairedDelayed and impaired
SocialAutistic traitsn/aPoor contactASD, short attention span, impulsive behaviourShort attention span, startle response to noisesPoor eye contactn/aAutistic traits, short attention spanPoor eye contactWell-integrated in a Montessori kindergardenHyperactive behaviour, autistic features as adultNormal
EpilepsyYesYesYesYesYesYesYesYesYesClinically suspected, normal EEGYesYes
Age at seizure onset8 months5 years5 months7 months10 months6 months2 months6 monthsNeonataln/a3 years4 years
Seizure typeConvulsive febrile and non-febrile seizuresGeneralised tonic–clonic seizures, myoclonian/aInfantile spasms, myoclonic seizuresFebrile seizures, multifocal seizuresInfantile spasms, tonic seizuresInfantile spasms, tonic seizuresInfantile spasms, intractable epilepsyCrytopgenic generalised epilepsy/Complex focal seizures with tonic–clonic generalisationFocal seizures
RefractoryNoNoNoYesYesNoYesYesn/a/NoNo
Brain imaging
Age at MRI5 yearsn/a2 months 3 weeks1 years 11 months and 7 years10 monthsn/a10 months8 years1 month3 years 7 months4 years 5 months and 12 years8years 4months17 months/25 months/4.5 years
Gyral patternNormalDysgyriaDysgyriaDysgyriaNormalDysgyriaDysgyriaNormalNormalDysgyriaCortical heterotopiaDysgyria
Severity/MildSevereMild/SevereSevere//Mild/n/a
Gradient/TemporoparietalInsular, parietalAnterior>posterior/DiffuseDiffuse//NormalRight parietal regionInsular, parietal
White matterNormalNormalNormalProminent Virchow-Robin spacesReducedSeverely reducedReducedNormalMildly reduced, posterior>anteriorNormalNormalProminent Virchow-Robin spaces
Lateral ventriclesNormalNormalEnlarged (left>right)EnlargedEnlargedEnlarged, hooked frontal hornsDilated, hooked frontal hornsEnlarged, asymmetric septal regionEnlarged occipital horns (left>right)NormalEnlarged occipital horns (left>right)Normal
Corpus callosumNormalDysmorphicPartial agenesisMildly dysmorphicHypoplasiaPartial agenesisDiffuse hypoplasiaHypoplasiaNormalNormalNormalThin body
Basal gangliaNormalNormalDysplasiaNormalNormalDysmorphicDysmorphicNormalMildly dysmorphicNormalNormalNormal
HippocampusNormalNormalNormalNormalNormalDysplasticNormalNormalNormalNormalNormalNormal
BrainstemNormalNormalNormalNormalNormalNormalNormalNormalNormalNormalNormalNormal
CerebellumNormalNormalSmall haemorrhage (left hemisphere)NormalNormalVermis hypoplasia and asymmetry, mild cortical atophyVermis hypoplasia and dysplasiaMild vermis hypoplasiaNormalNormalDysplastic vermisNormal
  • /, not applicable; ASD, autistic spectrum disorder; DCDA, dichorionic–diamniotic; EEG, electroencephalogram; GMFCS, Gross Motor Function Classification Scale; n/a, not available.