Supplementary Table 1: Summary of the key clinical, imaging and genetic features of the main polymicrogyria syndromes*
Syndrome
% of all
PMG
Clinical features
Bilateral
perisylvian
52
Without extension beyond
perisylvian cortex:
 Pseudobulbar palsy
 Speech delay (expressive)
 Feeding problems
 Mild intellectual disability
 Epilepsy (~ 80%) with onset
usually > 2 years
With extension beyond perisylvian
cortex:
 Infantile hypotonia
progressing to spastic
quadriplegia
 Global developmental delay
 Moderate to severe
intellectual disability
 Microcephaly (~ 50%)
 Occasional arthrogryposis
or talipes
 Epilepsy (~ 80%) with onset
usually in first year
Topography
Imaging features
Aetiology
Bilateral PMG maximal in the perisylvian
cortex with a severity spectrum from PMG
restricted to the posterior perisylvian
region to PMG extending variable
distances anteriorly, posteriorly and
inferiorly from the perisylvian region
X-linked with loci at:
 Xq28
 Xq21.33-q23
(SRPX2 gene)
 Xq27-q28
Autosomal loci at multiple
locations including:
 22q11.2
 1p36
? Asymmetric forms
secondary to mutations in the
TUBB2B gene at 6p25.2
Death of co-twin during
pregnancy (? ischaemic)
Peroxisomal disorders
Sylvian fissures extended posteriorly and
often oriented superiorly
Occasional asymmetric forms
Imaging features
Aetiology
Congenital hemiparesis
Mild or no intellectual disability
Epilepsy (~ 75%) with onset usually
> 5 years
Unilateral PMG maximal in the perisylvian
cortex, but may extend beyond into frontal,
parietal and temporal lobes
Sylvian fissures extended posteriorly and
often orientated superiorly
Occasional ipsilateral lateral ventricle
dilatation, white matter thinning,
Prominent subarachnoid space or septum
pellucidum agenesis
 Uncertain
 Possible locus at 22q11.2
Moderate to severe global
developmental delay
Microcephaly
Feeding problems
Spastic quadriplegia
Cortical visual impairment
Epilepsy (~ 80%) with onset usually
in first year
Bilateral symmetric PMG with a
generalised or near-generalised distribution
No gradient or region of maximal severity
Sylvian fissures often open anteriorly
White matter occasionally mildly thinned
Frequent lateral ventricular dilatation or
dysmorphism
Frequent corpus callosum abnormalities
 Uncertain
 Autosomal recessive or Xlinked possible
Syndrome
% of all
PMG
Clinical features
Unilateral
perisylvian
9
Generalised with
normal white
matter
5
Topography
Imaging features
Aetiology
Moderate to severe global
developmental delay
Microcephaly
Feeding problems
Spastic quadriplegia
Cortical visual impairment
Occasional sensorineural hearing loss
Epilepsy (~ 80%) with onset usually
in first year
Bilateral symmetric PMG with a
generalised or near-generalised distribution
No gradient or region of maximal severity
Sylvian fissures often open anteriorly
Diffuse high T2 signal in white matter
White matter often thinned
Occasional periventricular calcification
Frequent lateral ventricular dilatation or
dysmorphism
Frequent corpus callosum abnormalities
Occasional cerebellar vermis hypoplasia
 Autosomal recessive
 Peroxisomal disorders
 In utero cytomegalovirus
infection
Speech delay (expressive)
Mild to moderate intellectual
disability
Gross motor delay
Axial hypotonia during infancy
progressing later to mild spastic
quadriplegia
Microcephaly
Occasional visual impairment
Epilepsy in ~ 80%, usually
presenting in first year
Bilateral symmetric or asymmetric PMG
with an anterior > posterior gradient
Maximal in the frontal lobes
PMG does not extend beyond the central
sulcus and spares most of the perisylvian
region
Occasional lateral ventricular dilatation
Occasional thinning of frontal white matter
Occasional thinning of anterior corpus
callosum
Prominent perivascular spaces
 Uncertain
 X-linked or autosomal
recessive inheritance
possible
Syndrome
% of all
PMG
Clinical features
Generalised with
abnormal white
matter
8
Frontal only
5
Topography
Imaging features
Aetiology
Moderate to severe global
developmental delay
Spastic quadriplegia
Dysconjugate gaze secondary to
esotropia
Frequent cerebellar signs
Microcephaly (20%)
Seizures in ~ 100%, usually
presenting in the first year
Bilateral symmetric PMG with an anterior
> posterior gradient
Maximal in the frontal lobes
PMG extends beyond the central sulcus
into the parietal lobes and may involve the
superior bank of the Sylvian fissure
Frequent patchy high signal in white
matter
Frequent lateral ventricle dilatation
Frequent hypoplasia of pons
Frequent hypoplasia of cerebellar vermis
 Autosomal recessive
 GPR56 gene on 16q12.221
Moderate to severe global
developmental delay
Microcephaly (30%)
Occasional arthrogryposis or talipes
Axial hypotonia in infancy
progressing to spastic quadriplegia
Epilepsy in ~ 65%, usually before
age 5 years
Bilateral perisylvian PMG, which may
extend beyond Sylvian fissures (usually
into frontal lobes)
Perisylvian PMG may be asymmetric
Bilateral periventricular grey matter
heterotopia lining the bodies of the lateral
ventricles, usually with an anterior >
posterior predominance
Occasional hypoplasia of corpus callosum
Occasional hypoplasia of cerebellar vermis
 Uncertain
 Possible X-linked
inheritance
Syndrome
% of all
PMG
Clinical features
Frontoparietal
1
Periventricular
nodular heterotopia
/ bilateral
perisylvian
5
Topography
Imaging features
Aetiology
Mild to moderate global
developmental delay
Occasional macrocephaly
Axial hypotonia in infancy
Multiple congenital anomaly
syndrome in ~ 10%
Epilepsy in ~ 50%, with onset in first
or second decade
Periventricular grey matter heterotopia in
posterior bodies, atria or temporal horns of
lateral ventricles
Heterotopia usually bilateral but frequently
asymmetric
PMG in the cortex overlying the
periventricular grey matter
White matter thinned between
periventricular grey matter and PMG
Lateral ventricle dilated and dysmorphic
Abnormalities of posterior corpus callosum
common
Abnormalities of cerebellar vermis or
hemispheres common
 unknown
Mild global developmental delay
Normal intellect or mild intellectual
disability
Epilepsy in 100%, usually with onset
in the second decade
PMG lining the mesial occipital and
parietal gyri, often with extension
anteriorly into deep irregular gyri
PMG may be bilateral symmetric,
asymmetric or unilateral
Occasional mild thinning of adjacent white
matter
 unknown
Syndrome
% of all
PMG
Clinical features
Periventricular
nodular heterotopia
/ posterior
4
Parasagittal
parieto-occipital
4
Topography
* The information in this table is a synthesis of findings from the current study and those of previous studies.