Mutations in tubulin genes can have a severe impact on microtubule function and result in heterogeneous clinical presentations. [karger.com]

We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. [ejpn-journal.com]

[…] rare disease Polymicrogyria Disease definition Polymicrogyria (PMG) is a heterogenous group of cerebral cortical malformations characterized by excessive cortical folding and abnormal cortical layering that, depending on its topographic distribution, presents [orpha.net]

The remaining mutants all generated products present in the WT control, but in varying yield (d,e). Figure 4. [pubmed.ncbi.nlm.nih.gov]

• Epilepsy

  Polymicrogyria, a malformation of the cerebral cortex, frequently causes epilepsy. [ncbi.nlm.nih.gov]

  Myoclonic epilepsy of infancy Neonatal epilepsy syndrome Rare epilepsy West syndrome [se-atlas.de]

  In the majority of cases, epilepsy manifests in the first year of life with infantile spasms as the most common epilepsy syndrome. [gimjournal.org]

  Baulac and collaborators performed homozygosity mapping with subsequent exome sequencing in a family with temporo-occiopital polymicrogyria and epilepsy. [epilepsygenetics.net]

• Trisomy 21

  PKU), perinatal anoxia, toxic agents ( inc. drugs, alcohol (fetal alcohol syndrome), malnutrition, infectious agents (German measles, toxoplasmosis, chicken pox). o Down syndrome/Trisomy 21: � Most common single cause of birth defects. � Chromosome 21 [www2.gsu.edu]

• Strabismus

  […] interna, gene, psychomotor disorder, exon, caudate nucleus, structural protein, article, tubulin, female, head circumference, putamen, human, metabolism, gene sequence, nucleotide sequence, basal ganglia, chemistry, dyneins, neuroimaging, convergent strabismus [linknovate.com]

  Strabismus and nystagmus were the most common ocular motility disorders. Congenital fibrosis of the extraocular muscles (CFEOM) was exclusively depicted in the TUBB2B cohort. [gimjournal.org]

• Myopathy

  distal, CAP myopathy, Nemaline myopathy TPM3 CAP myopathy, Myopathy, congenital, with fiber- disproportion, Nemaline myopathy TRPV4 Brachyolmia (autosomal dominant type), Charcot-Marie-Tooth disease, Familial Digital arthropathy with brachydactyly, [genda.com.ar]

  MRE11A related Microcephaly, MSMO1 related Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy Microcephaly, TUBB2B related Miller Dieker lissencephaly syndrome Mitochondrial complex III deficiency, nuclear type 7 Mitochondrial myopathy [qlinics.com]

  […] research laboratories of Boston Children’s and other institutions, focuses on the description of novel mutations in patients with neuromuscular diseases and the application of new technologies to explore the pathogenesis and treatment of congenital myopathies [books.google.com]

  […] type 2 CEP57 Mulibrey nanism TRIM37 Multiple congenital anomalies-hypotonia-seizures syndrome type 1 PIGN Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects B3GAT3 Myhre syndrome SMAD4 Native American myopathy [centogene.com]

• Muscular Atrophy

  He is currently involved in multiple clinical trials of novel genetic interventions for the treatment of spinal muscular atrophy and Duchenne muscular dystrophy. [books.google.com]

  […] dystrophy, Myopathy with postural muscle atrophy, Reducing bod myopathy FKTN Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy, Muscular dystrophy-dystroglycanopathy (limb-girdle) GBA Gaucher disease GBE1 Glycogen storage disease GFPT1 [genda.com.ar]

• Suggestibility

  Patients and methods Patients We selected 128 consecutive patients (61 females and 67 males) with a cortical pattern that was either clearly suggestive of polymicrogyria or pachygyria. [nature.com]

  We propose that the cortical malformations associated with these genes represent a recognizable tubulinopathy-associated spectrum that ranges from lissencephalic to polymicrogyric cortical dysplasias, suggesting shared pathogenic mechanisms in terms of [ncbi.nlm.nih.gov]

  These observations suggest that the etiology for the neurological features must also be due to genes located proximal to SHANK3. [symbiosisonlinepublishing.com]

  Pathophysiology [ edit ] The genetic basis and pathophysiology of microlissencephaly are still not completely understood. [19] Most cases of microlissencephaly are described in consanguineous families suggesting an autosomal recessive inheritance. [7] [en.wikipedia.org]

  The authors suggest that YVS may represent the most extreme FIG4-related phenotype, while PMG and CTM4J might be milder phenotypes with deficits of different functional segments of the protein. [epilepsygenetics.net]

• Dystonia

  Our patient manifested juvenile-onset dystonia. Only 1 previously reported case with a TUBB2B p.R380P mutation presented with childhood-onset dystonia [13]. In contrast, dystonia has been more commonly associated with TUBB4A mutations [7]. [karger.com]

  TUBB2B mutation in an adult patient with myoclonus-dystonia. Case Rep Neurol. 2017; 9: 216-221 Wang H. Li S. Li S. et al. De novo mutated TUBB2B associated pachygyria diagnosed by medical exome sequencing and long-range PCR. Fetal Pediatr. [ejpn-journal.com]

  H-ABC- and dystonia-causing TUBB4A mutations show distinct pathogenic effects. Krajka V, Vulinovic F, Genova M, Tanzer K, Jijumon AS, Bodakuntla S, Tennstedt S, Mueller-Fielitz H, Meier B, Janke C, Klein C, Rakovic A. Krajka V, et al. [pubmed.ncbi.nlm.nih.gov]

  Accordingly, abnormalities of the muscular tone such as spastic di- or tetraplegia, muscular hypo- and dystonia occurred more frequently in the TUBA1A cohort (89.6% vs. 48.0%; P < 0.001). [gimjournal.org]

• Stroke

  She has a special interest in neonatal stroke and brain plasticity. Her work has been published in >400 publications. [books.google.com]

  Saundersfoot Medical Centre Skewen Medical Centre South East Wales Cancer Network South West Wales Cancer Network Speech & Language Therapists (Wales) - Autism St Mark's Dee View Surgery St Thomas and West Cross Surgeries St Thomas Surgery (Pembrokeshire) Stroke [wales.nhs.uk]

  This causes problems with functioning in the body much like how the effects of a stroke can affect the brain. The impairments that are seen as a result of PMG depend on what part of the brain is involved and how severe the deformity is. [pmgawareness.org]

  Funding Sources This work was supported by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke; project No.: NS003154). [karger.com]

• Encephalopathy

  Tubulinopathy Presenting as Developmental and Epileptic Encephalopathy. Hung KL, Lu JF, Su DJ, Hsu SJ, Wang LC. Hung KL, et al. Children (Basel). 2022 Jul 23;9(8):1105. doi: 10.3390/children9081105. Children (Basel). 2022. [pubmed.ncbi.nlm.nih.gov]

  Estopia is also known as dysconjugate gaze, and is a common feature of severe static encephalopathy. This differentiates BFPP from the other bilatieral polymicrogyria syndromes. [ipfs.io]

  ARID1A Coffin-Siris syndrome, Mental retardation ARID1B Coffin-Siris syndrome, Mental retardation ARSE Chondrodysplasia punctata X-linked recessive, brachytelephalangic type (CDPX1) ARX Corpus callosum, agenesis of, with abnormal genitalia, Epileptic encephalopathy [genda.com.ar]

  Evrard P, de Saint-Georges P, Kadhim HJ, Gadisseux J-F (1989) Pathology of prenatal encephalopathies. In: French J (ed) Child neurology and developmental disabilities. Paul H. Brookes, Baltimore, pp 153–176 Google Scholar 5. [link.springer.com]

• Meningism

  There is diffuse disorganization of the cortical plate with massive overmigration of cells within the meningeal spaces (I). From: Tubulinopathies Overview Copyright © 1993-2019, University of Washington, Seattle. [ncbi.nlm.nih.gov]

  Third, focal neuroglial ectopias into the meningeal spaces are often observed, indicating that tubulinopathies result from both abnormal lamination and overmigration through a defective glia limitans. [actaneurocomms.biomedcentral.com]

  M: meninges. Scale bars: (k–n) 500 μm, (o–r) 100 μm. Figure 2. [pubmed.ncbi.nlm.nih.gov]

He is currently involved in multiple clinical trials of novel genetic interventions for the treatment of spinal muscular atrophy and Duchenne muscular dystrophy. [books.google.com]

Treatment and management of PMG depend on the needs of the individual. Commonly used, but not limited too, are physical therapy for gross motor impairment, orthotic devices and surgery for those with spastic motor impairment. [pmgawareness.org]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

10: Q04.8 MeSH: D054220 OMIM: 606854 615752 300388 610031 613180 614833 612691 616531 Reference PMID: 18262290 Authors Guerrini R, Dobyns WB, Barkovich AJ Title Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment [genome.jp]

There is no specific treatment to get rid of this condition, but there are medications that can control the symptoms such as seizures, delayed development or weakened muscles as some of the noted effects. [en.wikipedia.org]

Diffuse bilateral polymicrogyria (DBP) is related to poor epilepsy prognosis, but most patients with DBP are not good candidates for resective epilepsy surgery and effectiveness of corpus callosotomy (CC), a palliative surgery, for patients without resective [ncbi.nlm.nih.gov]

Prognosis is developmental arrest at P3-5 mos. � Fatal by age 2 on average for MDS, by age 10 for ILS, usually due to pneumonia. � LIS1 controls the orientation of the mitotic spindle during corticogenesis by affecting dynein, affecting whether daughter [www2.gsu.edu]

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. [ipfs.io]

[…] usually present not present (MSGP is usually isolated) Prognosis [ edit ] Microlissencephaly usually leads to an early fatal outcome during the neonatal period. [28] Epidemiology [ edit ] Microlissencephaly is listed in Orphanet database as a rare disease [en.wikipedia.org]

However gross analysis shows an infected patient can have as little as one to all six of these layers missing. [4] Etiology The etiology of polymicrogyria is unclear. [ipfs.io]

Polymicrogyria can result from both genetic and environmental etiologies. It can occur as an isolated event, or as a symptom or part of other brain abnormalities. [pmgawareness.org]

These clinical features might have characterized a subpopulation with a specific subtype of polymicrogyria or a specific etiology, which is certainly not representative of the larger population of individuals with polymicrogyria, in which varied etiologic [ajnr.org]

These observations suggest that the etiology for the neurological features must also be due to genes located proximal to SHANK3. [symbiosisonlinepublishing.com]

Missense mutations in the absence of nonsense mutations, frameshifts, or genomic deletions support altered protein function, rather than haploinsufficiency, as the primary genetic etiology of these tubulin-related disorders[ 28 ]. [bmcresnotes.biomedcentral.com]

[15] There is not much information available about the epidemiology of microlissencepahly in literature. [en.wikipedia.org]

Thereby, we provide clinical and epidemiological data that are of particular interest for future diagnostic and therapeutic trials. [gimjournal.org]

Genetic epidemiology and nonsyndromic structural birth defects: from candidate genes to epigenetics. JAMA pediatrics, 168(4), 371-377. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Correa A (2010). [centogene.com]

Pathophysiology [ edit ] The genetic basis and pathophysiology of microlissencephaly are still not completely understood. [19] Most cases of microlissencephaly are described in consanguineous families suggesting an autosomal recessive inheritance. [7] [en.wikipedia.org]

Until recently, the different possible pathophysiological mechanisms underlying microlissencephaly remained poorly understood. [actaneurocomms.biomedcentral.com]

Article CAS Google Scholar Friocourt G, Marcorelles P, Saugier-Veber P, Quille ML, Marret S, Laquerrière A : Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly. Acta Neuropathol 2011; 121: 149–170. [nature.com]

PubMed PubMed Central View Article Google Scholar Friocourt G, Marcorelles P, Saugier-Veber P, Quille ML, Marret S, Laquerriere A: Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly. [bmcresnotes.biomedcentral.com]

The principal focus of his research has been elucidation of the pathogenesis of the major forms of brain injury in the newborn, and prevention of this injury. [books.google.com]

RELATED : Grant : Fondazione Cassa di Risparmio Pisa, Pisa, Italy (Project 133/11)*; European Union Seventh Framework Programme FP7/2007–2013 under the project DESIRE (Development and Epilepsy: Strategies for Innovative Research to improve diagnosis, prevention [ajnr.org]