View source for Polymicrogyria

{{Infobox medical condition (new)
| name          = Polymicrogyria
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| image         = Polymicrogyria arrows.JPG
| caption       = This child presented with seizures. The coronal true inversion recovery sequence shows thickened and disordered cortex in superior frontal and cingulate gyri bilaterally (arrow). There are small convolutions visible at the corticomedullary junction. The appearance is that of cortical dysplasia, with polymicrogyria more likely than pachygyria due to the small convolutions visible. There are also small foci of grey matter signal in the corpus callosum, deep to the dysplastic cortex (double arrows). These probably represent areas of grey matter heterotopia.
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'''Polymicrogyria''' ('''PMG''') is a condition that affects the development of the human [[brain]] by multiple small [[Gyrus|gyri]] ([[Microgyrus|microgyri]]) creating excessive folding of the brain leading to an abnormally thick [[Cerebral cortex|cortex]]. This abnormality can affect either one region of the brain or multiple regions.

The time of onset has yet to be identified; however, it has been found to occur before birth in either the earlier or later stages of brain development. Early stages include impaired proliferation and migration of [[neuroblast]]s, while later stages show disordered post-migration development.

The symptoms experienced differ depending on what part of the brain is affected. There is no specific treatment to get rid of this condition, but there are medications that can control the symptoms such as [[Epileptic seizure|seizures]], delayed development or weakened muscles as some of the noted effects.

== Syndromes ==
{{Original research|section|date=March 2017}}

Significant technological advances have been made within the past few decades that have allowed more extensive studies to be made regarding syndromes from conditions such as polymicrogyria. Research, imaging, and analysis has shown that distribution of polymicrogyria does not always appear to be random, which revealed different types polymicrogyria. A summary of clinical manifestations of each syndrome can be found below, in the section labelled "[[#Signs and symptoms|Clinical presentation]]".{{citation needed|date=January 2021}}

The main patterns of polymicrogyria are: perisylvian (61%), generalised (13%), frontal (5%), and parasagittal parieto-occipital (3%) and 11% is associated with [[gray matter heterotopia]] ([[grey matter]] is located in the [[white matter]] instead of usual location in the [[cerebral cortex]]).<ref name="pmid20403963">{{cite journal | vauthors = Leventer RJ, Jansen A, Pilz DT, Stoodley N, Marini C, Dubeau F, Malone J, Mitchell LA, Mandelstam S, Scheffer IE, Berkovic SF, Andermann F, Andermann E, Guerrini R, Dobyns WB | title = Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients | journal = Brain: A Journal of Neurology | volume = 133 | issue = Pt 5 | pages = 1415–27 | date = May 2010 | pmid = 20403963 | pmc = 2859156 | doi = 10.1093/brain/awq078 | url = }}</ref>

=== Bilateral frontal polymicrogyria (BFP) ===
{{Infobox medical condition (new)
| name          = Polymicrogyria
| synonyms      = PMG
| image         = Polymicrogyria.jpg
| caption       = Bilateral perisylvian polymicrogyria
}}

BFP appears to be a symmetrical polymicrogyria that extends anteriorly from the frontal poles to the posterior precentral gyrus, and inferiorly to the frontal operculum. Patients who had polymicrogyria distribution similar to this also experienced similar symptoms including delayed motor and language developments, spastic hemiparesis or quadriparesis, and forms of mild intellectual disability.{{citation needed|date=January 2021}}

=== Bilateral frontoparietal polymicrogyria (BFPP) ===
{{Main|Bilateral frontoparietal polymicrogyria}}

BFPP was one of the first discovered forms of polymicrogyria to have a gene identified linking to the syndromes caused. This gene is called [[GPR56]]. Symmetrical distribution is also evident in this form, but more distinctly, patients with BFPP were found to have [[atrophy]] of the [[cerebellum]] and [[brain stem]], as well as bilateral [[white matter]] abnormalities. BFPP is characterized by [[esotropia]], global development delay, pyramidal signs, cerebral signs, and seizures. Esotropia is also known as dysconjugate gaze, and is a common feature of severe static [[encephalopathy]]. This differentiates BFPP from the other bilateral polymicrogyria syndromes.{{citation needed|date=January 2021}}

=== Bilateral perisylvian polymicrogyria (BPP) ===
BPP is similar to the other types of polymicrogyria in that it is usually symmetrical, but BPP can vary among patients. BPP is characterized by its location; the cerebral cortex deep in the sylvian fissures is thickened and abnormally infolded, as well as the sylvian fissures extending more posteriorly up to the parietal lobes and more vertically oriented.<ref name="Nathan Source">{{cite journal|last1=Jansen|first1=A.|last2=Andermann|first2=E.|title=Genetics of the polymicrogyria syndromes|journal=Journal of Medical Genetics|pages=369–378|doi=10.1136/jmg.2004.023952|date=1 May 2005|pmid=15863665|volume=42|issue=5|pmc=1736054}}</ref> BPP has been classified into a grading system consisting of four different grades that describe the variations in severity:{{citation needed|date=January 2021}}

{{ordered list|type=none
  | Grade 1: Perisylvian polymicrogyria extends to either one or both poles
  | Grade 2: Perisylvian polymicrogyria extends past the perisylvian region, but not to either of the poles
  | Grade 3: Perisylvian polymicrogyria is contained in the perisylvian region only
  | Grade 4: Perisylvian polymicrogyria is contained in the posterior perisylvian region only
}}

The grades move from most severe (Grade 1) to least severe (Grade 4). Although BFPP was the first form of polymicrogyria to be discovered, BPP was the first form to be described and is also the most common form of polymicrogyria. The clinical characterizations of BPP "include pseudobulbar palsy with diplegia of the facial, pharyngeal and masticory muscles (facio-pharyngo-glosso-masticatory paresis), pyramidal signs, and seizures."<ref name="Nathan Source" /> These can result in drooling, feeding issues, restricted tongue movement, and [[dysarthria]].<ref name="Nathan Source" /> Disorders in language development have also been associated with BPP, but the extent of language disorder depends on the severity of cortical damage. Patients who have BPP can also have pyramidal signs that vary in severity, and can be either unilateral or bilateral.<ref name="Nathan Source" />

The sodium channel SCN3A has been implicated in BPP.<ref name="Oral Motor Development 2018">{{cite journal |last1=Smith |first1=RS |last2=Kenny |first2=CJ |last3=Ganesh |first3=V |last4=Jang |first4=A |last5=Borges-Monroy |first5=R |last6=Partlow |first6=JN |last7=Hill |first7=RS |last8=Shin |first8=T |last9=Chen |first9=AY |last10=Doan |first10=RN |last11=Anttonen |first11=AK |last12=Ignatius |first12=J |last13=Medne |first13=L |last14=Bönnemann |first14=CG |last15=Hecht |first15=JL |last16=Salonen |first16=O |last17=Barkovich |first17=AJ |last18=Poduri |first18=A |last19=Wilke |first19=M |last20=de Wit |first20=MCY |last21=Mancini |first21=GMS |last22=Sztriha |first22=L |last23=Im |first23=K |last24=Amrom |first24=D |last25=Andermann |first25=E |last26=Paetau |first26=R |last27=Lehesjoki |first27=AE |last28=Walsh |first28=CA |last29=Lehtinen |first29=MK |title=Sodium Channel SCN3A (Na<sub>V</sub>1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development. |journal=Neuron |date=5 September 2018 |volume=99 |issue=5 |pages=905–913.e7 |doi=10.1016/j.neuron.2018.07.052 |pmid=30146301|pmc=6226006 }}</ref>

=== Bilateral parasagittal parieto-occipital polymicrogyria (BPOP) ===
BPOP is located in the parasagittal and mesial regions of the parieto-occipital cortex. This form has been associated with IQ scores that range from average intelligence to mild intellectual disability, seizures, and cognitive slowing. The age of seizure onset has been found to occur anywhere from 20 months to 15 years, and in most cases the seizures were intractable (meaning hard to control).<ref name="Nathan Source" />

=== Bilateral generalised polymicrogyria (BGP) ===
BGP is most severe in the perisylvian regions, but occurs in a generalised distribution. Associated factors include a reduced volume of white matter and [[ventriculomegaly]]. BGP tends to show excessively folded and fused gyri of an abnormally thin cerebral cortex, and an absence of the normal six-layered structure. The abnormally thin cortex is a key factor that distinguishes this form of polymicrogyria from the others, which are characterized by an abnormally thick cortex. Most of the patients have cognitive and motor delay, spastic hemi- or quadriparesis, and seizures in varying degrees. The seizures also vary at age of onset, type, and severity. There have been pseudobulbar signs reported with BGP, which are also seen in patients with BPP. This association leads to the belief that there is overlap between patients with BGP and patients with grade 1 BPP.<ref name="Nathan Source" />

=== Unilateral polymicrogyria ===
The region in which unilateral polymicrogyria occurs has been generalized into different cortical areas. Features associated with this form of polymicrogyria are similar to the other forms and include spastic hemiparesis, intellectual disability in variable degrees, and seizures. The features depend on the exact area and extent to which polymicrogyria has affected the cortex. Patients who have unilateral polymicrogyria have been reported to also have electrical status epilepticus during sleep (EPES), and all had seizures.<ref name="Nathan Source" />

==Signs and symptoms==
The diagnosis of PMG is merely descriptive and is not a [[disease]] in itself, nor does it describe the underlying cause of the brain malformation.{{citation needed|date=January 2021}}

Polymicrogyria may be just one piece of a [[syndrome]] of developmental abnormalities, because children born with it may have a wide spectrum of other problems, including global [[developmental disabilities]], mild to severe [[intellectual disabilities]], [[motor skills|motor]] dysfunctions including [[speech]] and [[swallowing]] problems, [[respiratory system|respiratory]] problems, [[seizures]].<ref name="pmid24888723" /> Though it is difficult to make a predictable [[prognosis]] for children with the diagnosis of PMG, there are some generalized clinical findings according to the areas of the brain that are affected.{{citation needed|date=January 2021}}
* Bilateral frontal polymicrogyria (BFP) – Cognitive and motor delay, spastic [[quadriparesis]], epilepsy
* Bilateral frontoparietal polymicrogyria (BFPP) – Severe cognitive and motor delay, seizures, dysconjugate gaze, [[cerebellar]] dysfunction
* Bilateral perisylvian polymicrogyria (BPP) – [[Pseudobulbar]] signs, cognitive impairment, epilepsy, some with [[arthrogryposis]] or lower motor neuron disease
* Bilateral parasagittal parieto-occipital polymicrogyria (BPPP) – Partial seizures, some with intellectual developmental disorder
* Bilateral generalized polymicrogyria (BGP) – Cognitive and motor delay of variable severity, seizures

Rates of symptoms in PMG include 78% for [[epilepsy]], 70% for global developmental delay, 51% for [[spasticity]], 50% for [[microcephaly]], 45% for [[dysmorphic feature]]s (e.g., abnormal facies or hand, feet, or digital anomalies), and 5% for [[macrocephaly]].<ref name="pmid24888723" /> In the BPP subtype of PMG, up to 75% may have mild to moderate intellectual disability.<ref name="pmid24888723" />

==Cause==
The cause of polymicrogyria is unclear. It is generally agreed that PMG occurs during late neuronal migration (when majority of the neurons arrived at cerebral cortex after their starting points around the [[ventricular system]] of the brain) or early cortical organization of fetal development. Evidence for both genetic and non-genetic causes exists.<ref name="pmid24888723"/>

Chromosomal abnormalities have been identified in PMG such as [[DiGeorge syndrome|22q11.2 deletion]] (characterised by bilateral perisylvian PMG, heart defects, facial dysmorphism, [[microcephaly]]) and [[1p36 deletion syndrome|1p36 deletion]] (bilateral perisylvian PMG, intellectual disability, dysmorphic facial features and microcephaly).<ref name="Stutterd 2022">{{cite book |last1=Stutterd |first1=CA |last2=Dobyns |first2=WB |last3=Jansen |first3=A |last4=Mirzaa |first4=G |last5=Leventer |first5=RJ |title=Polymicrogyria Overview |date=1993–2022 |publisher=[[GeneReviews]] |location=Seattle, US |pmid=20301504 |url=https://www.ncbi.nlm.nih.gov/books/NBK1329/ |access-date=3 April 2022}}</ref> Apart from that, mutations in more than 30&nbsp;[[gene]]s have been associated with PMG.<ref name="pmid24888723" /> Common genes associated with PMG are TUBA1A and PIK3R2.<ref name="pmid33604570">{{cite journal |vauthors=Stutterd CA, Brock S, Stouffs K, Fanjul-Fernandez M, Lockhart PJ, McGillivray G, Mandelstam S, Pope K, Delatycki MB, Jansen A, Leventer RJ |title=Genetic heterogeneity of polymicrogyria: study of 123 patients using deep sequencing |journal=Brain Communications |volume=3 |issue=1 |article-number=fcaa221 |date=2021 |pmid=33604570 |pmc=7878248 |doi=10.1093/braincomms/fcaa221 |url=}}</ref> Association with the gene [[WDR62]] (diffuse or asymmetric PMG) and [[SCN3A]] has also been identified,<ref name=pmid21496009>{{cite journal|last=Bhat|first=V |author2=Girimaji, SC |author3=Mohan, G |author4=Arvinda, HR |author5=Singhmar, P |author6=Duvvari, MR |author7=Kumar, A|title=Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations|journal=Clinical Genetics|date=Apr 15, 2011|pmid=21496009|doi=10.1111/j.1399-0004.2011.01686.x|pages=532–40|volume=80|issue=6|s2cid=45190332 }}</ref><ref name=Murdock2011>{{cite journal |vauthors = Murdock DR, Clark GD, Bainbridge MN, Newsham I, Wu YQ, Muzny DM, Cheung SW, Gibbs RA, Ramocki MB | year = 2011 | title = Whole-exome sequencing identifies compound heterozygous mutations in WDR62 in siblings with recurrent polymicrogyria | journal = Am J Med Genet A | volume = 155| issue = 9| pages = 2071–2077| doi = 10.1002/ajmg.a.34165 | pmid = 21834044| pmc = 3616765}}</ref><ref>{{cite journal |pmid=30146301 | doi=10.1016/j.neuron.2018.07.052 | pmc=6226006 | volume=99 | title=Sodium Channel SCN3A (Na<sub>V</sub>1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development | year=2018 | author=Smith RS, Kenny CJ, Ganesh V, Jang A, Borges-Monroy R, Partlow JN, Hill RS, Shin T, Chen AY, Doan RN, Anttonen AK, Ignatius J, Medne L, Bönnemann CG, Hecht JL, Salonen O, Barkovich AJ, Poduri A, Wilke M, de Wit MCY, Mancini GMS, Sztriha L, Im K, Amrom D, Andermann E, Paetau R, Lehesjoki AE, Walsh CA, Lehtinen MK | journal=Neuron | issue=5 | pages=905–913.e7}}</ref><ref name="Oral Motor Development 2018"/> as well as other ion channels such as KCN, CACNA, GRIN, and GABAR.<ref name="Ion Channel Functions in Early Brai">{{cite journal |last1=Smith |first1=RS |last2=Walsh |first2=CA |title=Ion Channel Functions in Early Brain Development. |journal=Trends in Neurosciences |date=February 2020 |volume=43 |issue=2 |pages=103–114 |doi=10.1016/j.tins.2019.12.004 |pmid=31959360 |pmc=7092371 }}</ref> Other genes implicated are: [[GPR56]] (Bilateral frontoparietal PMG), [[Tubulin|TUBB2B]] (anterior predominant PMG), [[NDE1]] (Diffuse PMG), [[AKT3]] (Bilateral perisylvian PMG), and [[P110α|PIK3CA]] (Bilateral perisylvian PMG).<ref name="Stutterd 2022"/>

Non-genetic causes include defects in placental oxygenation and in association with congenital infections, particularly [[cytomegalovirus]], [[syphilis]], and [[varicella zoster virus]].<ref name="pmid24888723"/>{{Additional citation needed|date=December 2020}}

== Pathology ==
Polymicrogyria is a disorder of [[neuronal]] migration, resulting in structurally abnormal [[cerebral hemispheres]]. The Greek roots of the name describe its salient feature: many [poly] small [micro] gyri (convolutions in the surface of the brain). It is also characterized by shallow [[sulcus (neuroanatomy)|sulci]], a slightly thicker [[Cerebral cortex|cortex]], neuronal [[Heterotopia (medicine)|heterotopia]] and enlarged [[Ventricular system|ventricles]]. When many of these small folds are packed tightly together, PMG may resemble [[pachygyria]] (a few "thick folds" - a mild form of [[lissencephaly]]).{{citation needed|date=December 2020}}

The pathogenesis of polymicrogyria is still being researched for understanding though it is historically [[heterogeneous]]-4. It results from both genetic and destructive events. While polymicrogyria is associated with genetic mutations, none of these are the sole cause of this abnormality. The cortical development of mammals requires specific cell functions that all involve [[microtubules]], whether it is because of [[mitosis]], specifically [[cell division]], [[cell migration]] or [[neurite]] growth. Some mutations that affect the role of microtubules and are studied as possible contributors, but not causes, to polymicrogyria include [[TUBA1A]] and TUBB2B.<ref>{{Cite journal|last=Kato|first=Mitsuhiro|date=2015-01-01|title=Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias|journal=Frontiers in Neuroscience|volume=9|page=181|doi=10.3389/fnins.2015.00181|issn=1662-4548|pmc=4439546|pmid=26052266|doi-access=free}}</ref> TUBB2B mutations are known to contribute to polymicrogyria either with or without congenital [[fibrosis]] or the external [[ocular]] muscles, as well as bilateral perisylvian.{{citation needed|date=December 2020}}

[[File:GPR56.png|thumb|GPR56 protein structuregreen: signal peptideyellow: N-Glycosylation siteblue: GPS motiforange bracket: 108-177 aa STPpink bracket: 27-160 aa Ligand binding domain Referenced article: {{cite journal | pmid=23001883 | doi=10.1007/s12035-012-8343-0 | volume=47 | issue=1 | title=GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration | pmc=3538897 | year=2013 | journal=Mol. Neurobiol. | pages=186–96 |vauthors=Singer K, Luo R, Jeong SJ, Piao X }}]]
The gene GPR56 is a member of the adhesion G protein-coupled receptor family and is directly related to causing Bilateral frontoparietal polymicrogyria, ([[Bilateral frontoparietal polymicrogyria|BFPP]])-6. Other genes in the G protein-coupled receptor family have effects with this condition as well such as the outer brain development, but not enough is known to carry out all the research properly so the main focus is starting with the specific GR56 gene within this category. This malformation of the brain is a result of numerous small gyri taking over the surface of the brain that should otherwise be normally convoluted. This gene is currently under studies to help identify and contribute to the knowledge about this condition. It is studied to provide information on the causes along with insight into the mechanisms of normal cortical development and the regional patterning of the cerebral cortex using magnetic resonance imagine, MRI. Specifically found to polymicrogyria due to mutation of this gene are myelination defects. GPR56 is observed to be important for myelinations due to a mutation in this gene results in reduced white matter volume and signal changes as shown in MRI's. While the cellular roles of GPR56 in myelination remains unclear, this information will be used to further other studies done with this gene.{{citation needed|date=December 2020}}

Another gene that has been associated with this condition is GRIN1 and GRIN2B.<ref name=Fry2018>{{cite journal|doi=10.1093/brain/awx358|title=De novo mutations in GRIN1 cause extensive bilateral polymicrogyria|year=2018|last1=Fry|first1=Andrew E.|last2=Fawcett|first2=Katherine A.|last3=Zelnik|first3=Nathanel|last4=Yuan|first4=Hongjie|last5=Thompson|first5=Belinda A N.|last6=Shemer-Meiri|first6=Lilach|last7=Cushion|first7=Thomas D.|last8=Mugalaasi|first8=Hood|last9=Sims|first9=David|last10=Stoodley|first10=Neil|last11=Chung|first11=Seo-Kyung|last12=Rees|first12=Mark I.|last13=Patel|first13=Chirag V.|last14=Brueton|first14=Louise A.|last15=Layet|first15=Valérie|last16=Giuliano|first16=Fabienne|last17=Kerr|first17=Michael P.|last18=Banne|first18=Ehud|last19=Meiner|first19=Vardiella|last20=Lerman-Sagie|first20=Tally|last21=Helbig|first21=Katherine L.|last22=Kofman|first22=Laura H.|last23=Knight|first23=Kristin M.|last24=Chen|first24=Wenjuan|last25=Kannan|first25=Varun|last26=Hu|first26=Chun|last27=Kusumoto|first27=Hirofumi|last28=Zhang|first28=Jin|last29=Swanger|first29=Sharon A.|last30=Shaulsky|first30=Gil H.|journal=Brain|volume=141|issue=3|pages=698–712|pmid=29365063|pmc=5837214|display-authors=29}}</ref><ref name="Ion Channel Functions in Early Brai"/>

==Diagnosis==
The effects of PMG can be either focal or widespread. Although both can have physiological effects on the patient, it is hard to determine PMG as the direct cause because it can be associated with other brain malformations. Most commonly, PMG is associated with Aicardi and Warburg micro syndromes.<ref name=":0">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK1329/|title=Polymicrogyria Overview|last1=Chang|first1=Bernard|last2=Walsh|first2=Christopher A.|last3=Apse|first3=Kira|last4=Bodell|first4=Adria|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301504|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora J.H.|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Fong|editor-first8=Chin-To|editor-last9=Mefford|editor-first9=Heather C.}}</ref> These syndromes both have frontoparieto polymicrogyria as their anomalies. To ensure proper diagnosis, doctors thus can examine a patient through neuroimaging or neuropathological techniques.<ref name=":0" />

===Neuroimaging techniques===
Pathologically, PMG is defined as "an abnormally thick cortex formed by the piling upon each other of many small gyri with a fused surface."<ref>{{Cite journal|last1=Squier|first1=Waney|last2=Jansen|first2=Anna|date=2014-01-01|title=Polymicrogyria: pathology, fetal origins and mechanisms|journal=Acta Neuropathologica Communications|volume=2|page=80|doi=10.1186/s40478-014-0080-3|issn=2051-5960|pmc=4149230|pmid=25047116 |doi-access=free }}</ref> To view these microscopic characteristics, [[magnetic resonance imaging]] (MRI) is used. First physicians must distinguish between polymicrogyria and pachygyria. Pachygria leads to the development of broad and flat regions in the cortical area, whereas the effect of PMG is the formation of multiple small gyri. Underneath a computerized tomography ([[CT scan]]) scan, these both appear similar in that the cerebral cortex appears thickened. However, MRI with a T1 weighted inversion recovery will illustrate the gray-white junction that is characterized by patients with PMG.<ref name=":0" /> An MRI is also usually preferred over the CT scan because it has sub-millimeter resolution. The resolution displays the multiple folds within the cortical area, which is continuous with the neuropathology of an infected patient.{{citation needed|date=December 2020}}

===Neuropathological techniques===
Gross examination exposes a pattern of many small gyri clumped together, which causes an irregularity in the brain surface.<ref name=":0" /> The cerebral cortex, which in normal patients is six cell layers thick, is also thinned. As mentioned prior, the MRI of an affected patient shows what appears to be a thickening of the cerebral cortex because of the tiny folds that aggregate causing a more dense appearance. However, gross analysis shows that an affected patient can have as few as one to all six of these layers missing.<ref name=":0" />

==Treatment==
The PMG malformation cannot be reversed, but the symptoms can be treated. The removal of affected areas through hemispherectomy has been used in some cases to reduce the amount a seizure activity. Few patients are candidates for surgery.<ref>{{cite journal|journal=Epilepsia|volume=57|issue=1|doi=10.1111/epi.13264|title=Surgical management of medically refractory epilepsy in patients with polymicrogyria|year=2016|last1=Wang|first1=Doris D.|last2=Knox|first2=Renatta|last3=Rolston|first3=John D.|last4=Englot|first4=Dario J.|last5=Barkovich|first5=A. James|last6=Tihan|first6=Tarik|last7=Auguste|first7=Kurtis I.|last8=Knowlton|first8=Robert C.|last9=Cornes|first9=Susannah B.|last10=Chang|first10=Edward F.|pages=151–161|pmid=26647903|pmc=5237579}}</ref> The global developmental delay that affects 94% can also be mitigated in some patients with occupational, physical, and speech therapies. The important aspect to realize is PMG affects each patient differently and treatment options and mitigation techniques will vary.<ref>Journal of Medical Genetics; London Vol. 42, Iss. 5,</ref>

== Epidemiology ==
The incidences of PMG and its different forms are unknown.<ref name="Villard2002–2004">{{citation | last1 = Villard | first1 = Laurent | title = Polymicrogyria | orig-date = October 2002 | date = August 2004 | encyclopedia = Orphanet Encyclopedia | publisher = Orphanet | url = https://www.orpha.net/data/patho/GB/uk-PMG.pdf}}</ref> However, the frequency of [[cortical dysplasia]] in general has been estimated to be 1 in 2,500 newborns.<ref name="Villard2002–2004" /> PMG is one of the best-known and most common malformations of cortical development, accounting for 20% of all cases.<ref name="Villard2002–2004" /><ref name="pmid24888723">{{cite journal | vauthors = Stutterd CA, Leventer RJ | title = Polymicrogyria: a common and heterogeneous malformation of cortical development | journal = Am J Med Genet C Semin Med Genet | volume = 166C | issue = 2 | pages = 227–39 | date = June 2014 | pmid = 24888723 | doi = 10.1002/ajmg.c.31399 | s2cid = 24534275 | url = }}</ref> In the largest series of PMG cases, the bilateral perisylvian pattern was the most common topological pattern (52% of cases) followed by the unilateral perisylvian pattern (9% of cases).<ref name="pmid24888723" />

== History ==
Limited information was known about cerebral disorders until the development of modern technologies. Brain imaging and [[DNA sequencing|genetic sequencing]] greatly increased the information known about polymicrogyria from the early 2000s onwards.<ref name=":1">{{Cite journal|last=Barkovich|first=A. James|date=2010-06-01|title=Current concepts of polymicrogyria|journal=Neuroradiology|volume=52|issue=6|pages=479–487|doi=10.1007/s00234-009-0644-2|issn=1432-1920|pmc=2872023|pmid=20198472}}</ref> Understanding about development, classification and localization of the disorder have greatly improved.<ref name=":1" /> For instance, localization of specific cortex regions affected by the disease was determined. This allowed for clinical symptoms of patients to be linked with localized cortex areas affected.<ref name=":1" /> A gene that was identified to be a contributor to [[bilateral frontoparietal polymicrogyria]] was [[GPR56]].{{citation needed|date=December 2020}}

==See also==
* [[Augmentative and alternative communication]]
* [[Bilateral frontoparietal polymicrogyria]] (genetic lesion)
* [[Epilepsy Phenome/Genome Project]]

==References==
{{Reflist}}

{{Medical resources
| DiseasesDB      = 33975
| ICD10           = Q04.3
| ICD9            = {{ICD9|742.2}}
| ICDO            =
| OMIM            =
| MedlinePlus     =
| eMedicineSubj   =
| eMedicineTopic  =
| MeshID          = D054220
| GeneReviewsNBK  = NBK1329
| GeneReviewsName = Polymicrogyria Overview
| Scholia         = Q2991265
| Orphanet        = 35981
}}
{{Congenital malformations and deformations of nervous system}}

[[Category:Congenital disorders of nervous system]]
[[Category:Tubulinopathies]]