O termo lisencefalia abrange um grupo de malformações raras que compartilham a característica comum de anomalias no aparecimento de circunvoluções cerebrais (caracterizadas por simplificação ou ausência de dobramento) associadas à organização anormal das camadas corticais como resultado de defeitos de migração neuronal durante a embriogênese.
Introdução
O que você precisa saber de cara
O termo lisencefalia abrange um grupo de malformações raras que compartilham a característica comum de anomalias no aparecimento de circunvoluções cerebrais (caracterizadas por simplificação ou ausência de dobramento) associadas à organização anormal das camadas corticais como resultado de defeitos de migração neuronal durante a embriogênese.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 181 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 461 características clínicas mais associadas, ordenadas por frequência.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
24 genes identificados com associação a esta condição.
Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate
Phosphoglycerate dehydrogenase deficiency
An autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures.
The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, epithelial polarization, and epithelium branching morphogenesis (By similarity). Required for the formation of photoreceptor ribbon synapses, and long-term maintenance of inhibitory synapses in cerebellar Purkinje cel
Secreted, extracellular spaceSecreted, extracellular space, extracellular matrix, basement membraneSynapseCell membraneCytoplasm, cytoskeletonNucleus, nucleoplasmCell membrane, sarcolemmaPostsynaptic cell membrane
Muscular dystrophy-dystroglycanopathy limb-girdle C9
An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with intellectual disability without structural brain anomalies.
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral si
NucleusCytoplasmMelanosome
Transcriptional repressor (PubMed:12052894, PubMed:15231840). Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3' (PubMed:15231840). May act as a tumor suppressor (PubMed:20154726). Involved in development of head, face, limbs and ventral body wall (By similarity). Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses (PubMed:16269335). The specific target gene promoter association seems to be depend
Nucleus
Catalyzes the last irreversible step in the biosynthesis of L-serine from carbohydrates, the dephosphorylation of O-phospho-L-serine to L-serine (PubMed:12213811, PubMed:14673469, PubMed:15291819, PubMed:25080166, PubMed:9222972). L-serine can then be used in protein synthesis, to produce other amino acids, in nucleotide metabolism or in glutathione synthesis, or can be racemized to D-serine, a neuromodulator (PubMed:14673469). May also act on O-phospho-D-serine (Probable)
Cytoplasm, cytosol
Phosphoserine phosphatase deficiency
An autosomal recessive disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome.
Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3 (PubMed:28973932). Involved in the positive regulation of proteasomal protein degradation in the endoplasmic re
MembraneEndoplasmic reticulum
Lissencephaly 8
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive.
Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, hun
CytoplasmNucleusCell membranePerikaryonCell projection, lamellipodiumCell projection, growth conePostsynaptic densitySynapse
Lissencephaly 7, with cerebellar hypoplasia
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS7 patients manifest lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy.
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity)
Cytoplasm, cytoskeleton
Deafness, autosomal dominant, 20
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damage
Cytoplasm, cytoskeletonNucleus
Dystonia-deafness syndrome 1
An autosomal dominant form of dystonia with juvenile onset, associated with congenital or childhood-onset sensorineural deafness. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. Some DDS1 patients have dysmorphic features, skeletal anomalies, and/or mild developmental delay with impaired intellectual development.
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:24891604, PubMed:30970241). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:24891604, PubMed:30970241). RAB18 is required for the localization of ZFYVE1 t
Endoplasmic reticulum membraneGolgi apparatus, cis-Golgi network membraneLipid dropletApical cell membrane
Warburg micro syndrome 3
A rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine (PubMed:36851825, PubMed:37627284). Catalyzes the second step, that is the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate (PubMed:36851825, PubMed:37627284). Acts as an inhibitor of ferroptosis in response to interferon-gamma (IFNG) by promotin
Phosphoserine aminotransferase deficiency
Characterized biochemically by low plasma and cerebrospinal fluid concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation.
Plays an essential role in neuronal cell migration
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin
Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, flagellum axoneme
Lissencephaly 3
A classic type lissencephaly associated with psychomotor retardation and seizures. Features include agyria or pachygyria or laminar heterotopia, severe intellectual disability, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem.
Regulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins (PubMed:9733780, PubMed:39779760). The complex has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and has guanine nucleotide exchange factor (GEF) activity towards RAB18 (PubMed:9733780, PubMed:39779760, PubMed:24891604). The Rab3GAP com
CytoplasmEndoplasmic reticulum
Martsolf syndrome 1
An autosomal recessive disease characterized by congenital cataracts, intellectual disability, and hypogonadism.
Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule
CytoplasmCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindle poleCytoplasm, cytoskeletonCytoplasm, cytoskeleton, spindle
Lissencephaly 6, with microcephaly
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS6 features include hypoplasia of the corpus callosum, severe microcephaly and developmental delay.
Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the
Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, microtubule organizing center, centrosomeChromosome, centromere, kinetochoreCytoplasm, cytoskeleton, spindleCleavage furrowCytoplasmic vesicle membrane
Lissencephaly 4 with microcephaly
A neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly, and profound intellectual disability.
Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins (PubMed:9030515, PubMed:10859313, PubMed:39779760). Has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43 (PubMed:10859313, PubMed:9030515, PubMed:39779760). Additionally, it has guanine nucleotide exchange factor (GEF) activity towards RAB18
CytoplasmEndoplasmic reticulumGolgi apparatus, cis-Golgi network
Warburg micro syndrome 1
A rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarit
Cytoplasm, cytoskeletonCytoplasmGolgi apparatusCell membraneCell projection, ruffle membrane
Lissencephaly 9 with complex brainstem malformation
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly.
Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment. Regulates microtubule function in neurons and neuronal migration. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation. Affects migration of sympathetic preganglionic neurons in the spinal
Secreted, extracellular space, extracellular matrix
Lissencephaly 2
A classic type lissencephaly associated with ataxia, intellectual disability, seizures and abnormalities of the cerebellum, hippocampus and brainstem.
GTPase-activating protein (GAP) specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude (PubMed:23236136). Also shows GAP activity for RAB18 GTPase (PubMed:26063829). Promotes RAB18 dissociation from the endoplasmic reticulum (ER) membrane into the cytosol, probably through stimulating RAB18 GTP-hydrolysis (PubMed:26063829). Involved in maintaining endoplasmic reticulum structure (PubMed:24891604)
Membrane
Warburg micro syndrome 4
A form of Warburg micro syndrome, a rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, sign
CytoplasmCell projection, neuron projection
Lissencephaly, X-linked 1
A classic lissencephaly characterized by intellectual disability and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.
Transcription factor (PubMed:22194193, PubMed:31691806). Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of target genes, such as histone demethylase KDM5C (PubMed:22194193, PubMed:31691806). Positively modulates transcription of KDM5C (PubMed:31691806). Activates expression of KDM5C synergistically with histone lysine demethylase PHF8 and perhaps in competition with transcription regulator ZNF711; synergy may be related to enrichment of histone H3K4me3 in regulatory element
Nucleus
Lissencephaly, X-linked 2
A classic type lissencephaly associated with abnormal genitalia. Patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigra
Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindleNucleus membrane
Lissencephaly 1
A classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum.
Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Involved in the organization of the laminar architecture of the cerebral cortex (PubMed:23472759). It is probably required for the integrity of the basement membrane/glia limitans that serves as an anchor point for the endfeet of radial glial cells and as a physical bar
Secreted, extracellular space, extracellular matrix, basement membrane
Lissencephaly 5
An autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development.
Variantes genéticas (ClinVar)
375 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 979 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
120 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Lisencefalia
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Genetic landscape and phenotypic correlations of lissencephaly: prenatal and postnatal insights.
Lissencephaly (LIS) is a spectrum of cortical malformations including agyria, pachygyria and subcortical band heterotopia, which arises from aberrant neuronal migration and is associated with severe neurodevelopmental impairments. Despite advancements in prenatal imaging, diagnosing LIS remains challenging. Genetic factors play a crucial role in LIS, involving multiple genes and signalling pathways, yet research on prenatal diagnosis and the genetic basis is still limited. This study aimed to assess the diagnostic yield of whole exome sequencing (WES) in LIS and to examine genotype-phenotype correlations, addressing the challenge of 'phenotype lag' in prenatal LIS diagnosis. This study included 20 fetuses with LIS suggested by prenatal imaging and 20 children with LIS diagnosed after birth; all cases were diagnosed by magnetic resonance imaging and underwent genetic testing. In addition, a literature review was conducted and 80 studies were included, of which 1 was used to compare detection efficacy and 79 studies totalling 210 cases were used to assess genotype-phenotype correlation. In the prenatal cohort, 85.0% (17/20) of cases exhibited concurrent anomalies, predominantly ventriculomegaly (50.0%) and microcephaly (25.0%). In the postnatal cohort, the most common phenotypes were epilepsy (80.0%, 16/20) and global developmental delay (65.0%, 13/20), with half of the cases (10/20) showing no abnormalities in the prenatal period. The diagnostic yields were 55.0% (11/20) and 65.0% (13/20), respectively, with PAFAH1B1 point mutations or 17p13.3 microdeletions being the predominant genetic variant in both cohorts, accounting for 31.3% (prenatal) and 25.5% (postnatal) of cases, respectively. DARS2 and NPRL3 were reported to be associated with LIS for the first time in this study. Literature synthesis revealed an overall diagnostic yield of 79.04%, dominated by PAFAH1B1 (26.3%), DYNC1H1 (11.9%), and DCX (10.2%). By reviewing the prenatal images, up to 48.05% (74/154) of the cases had no specific findings in the prenatal period, and the most common presentations were ventriculomegaly/hydrocephalus (52.63%) and head circumference anomalies (29.82%). This study highlights the significant genetic heterogeneity, phenotypic complexity and diagnostic challenges of LIS by integrating data from our cohort and the published literature. We developed a comprehensive genetic aetiology classification framework for LIS and identified novel associations with non-canonical genes such as NPRL3 and DARS2. With a high molecular diagnostic yield of 79.04%, we recommend WES as the first-line genetic test. Furthermore, the establishment of an integrated prenatal imaging-molecular diagnostic system, along with a postnatal multidisciplinary model, is crucial for improving prognosis assessment, clinical decision-making and genetic counselling.
Bi-allelic variants in NRDC cause a neurodevelopmental disorder characterized by neonatal lethality, microcephaly, and brain abnormalities.
Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), eye/visual abnormalities (5/7), and abnormal brain imaging studies ranging from diffuse atrophy to lissencephaly (8/11). The identified variants include two splice, three frameshift, and three missense variants. RT-PCR from affected individual fibroblasts and a minigene assay in HEK293T cells demonstrate that the splice variants led to exon skipping of NRDC. To further investigate the pathogenicity of the variants in vivo, we used the Drosophila Nrdc (dNrdc) mutant model. dNrdc null mutants caused developmental lethality, which is fully rescued by wild-type human NRDC. Studies in the Drosophila dNrdc mutant models showed that both splice variants and frameshift variants cause severe loss of function, leading to lethality, whereas missense variants cause partial lethality and short lifespan, consistent with less severe phenotype. Our data establish that homozygous variants in NRDC are pathogenic, leading to highly lethal and severe neurodevelopmental disorder in humans.
Roles of microtubules and LIS1 in dynein transport machinery assembly.
Cytoplasmic dynein-1, a microtubule (MT)-based motor protein, requires dynactin and a coiled-coil adaptor to form the processive dynein-dynactin-adaptor (DDA) complex1,2. The roles of MTs and dynein regulator lissencephaly-1 (LIS1) in DDA assembly have remained elusive. Here we use cryo-electron microscopy to determine the structural basis of MT- and LIS1-mediated DDA assembly. We show that an adaptor-independent dynein-dynactin complex spontaneously forms on MTs with an intrinsic 2:1 stoichiometry in a highly efficient manner, driven by parallel alignment of dynein tails upon MT binding. Adaptors can wedge into and exchange within the assembled MT-bound dynein-dynactin complex; these processes are enabled by relative rotations between dynein and dynactin and facilitated by the dynein light-intermediate chains that assist the adaptor 'search' mechanism. Although LIS1 is dispensable for efficient DD(A)-MT assembly, its presence expands the conformational landscape of DD(A) assemblies on MTs. Cryo-electron microscopy reveals that LIS1 bridges dynactin p150glued and dynein in both the closed Phi-like and open prepowerstroke states, stabilizing low-MT-affinity intermediates that tether dynein molecules in proximity to MTs and prime them for subsequent DD(A) assembly through alternative pathways. These findings demonstrate the dynamic adaptability of the dynein transport machinery and the coordinated roles of MTs and LIS1 in DDA assembly.
Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders.
ASTN1 encodes astrotactin 1, a neuronal-glial ligand in the developing brain that promotes neuronal migration along radial glia in brain structures with laminar organization, such as the cerebral cortex, hippocampus, and cerebellum. In mouse models, disruption of Astn1 results in neuronal migration deficits, a mild reduction in cerebellar volume, and balance and coordination deficits. In humans, bi-allelic ASTN1 variants have been identified in nine individuals with neurodevelopmental disorders (NDDs) with or without brain malformations. ASTN1 additionally interacts with astrotactin 2 (ASTN2) to implement neuronal migration; ASTN2 deletions associate with NDDs with reduced penetrance. Here, we describe eighteen individuals with NDDs from twelve unrelated families with bi-allelic, ultra-rare, predicted damaging variants in ASTN1 and one individual with heterozygous variants in both ASTN1 and ASTN2. We expand the clinical phenotypic descriptions of ASTN1-related NDDs, which range from mild to profound developmental delay or intellectual disability and can be associated with autism, attention-deficient hyperactivity disorder (ADHD), and epilepsy. Other recurrent abnormalities include dysmorphic facial features, hypotonia, spasticity, and ataxia. Additionally, we add to the neuroradiographic phenotype of this condition, which can be normal, mildly dysmorphic (a thin corpus callosum and cerebellar dysgenesis), or severely dysmorphic (polymicrogyria and lissencephaly). Remarkably, three genetic models of multilocus pathogenic variation (MPV), including tri-allelic, double heterozygous, and double homozygous due to distributive absence of heterozygosity (AOH), were observed. This ASTN1 allelic series characterizes the consequences of perturbations in radial-glia-guided neuronal migration in humans, the phenotypic spectrum of ASTN1-related NDDs, and the contribution of MPV to the genetic basis of NDDs.
A rare complication of vagus nerve stimulation surgery: the Horner Syndrome. Case report and systematic review.
Vagus nerve stimulation (VNS) is a therapy used for drug-resistant epilepsy, refractory status epilepticus and treatment-resistant depression. VNS can reduce seizure severity and frequency, improving quality of life. It is generally well tolerated, with rare complications, which can be early (surgical) or late (device-related or stimulation-related). Common side effects include vocal cord issues, cough, and infections. We present Horner syndrome as a rare complication of VNS caused by damage to the sympathetic innervation of the ipsilateral eye and characterized by ptosis, miosis and rarely anhidrosis. MATERIALS AND METHODS: This was a case report and systematic review of the available literature according to PRISMA guidelines. The examined databases are Medline/PubMed, Scopus and Web of Science. RESULTS: A fourteen-year-old girl with drug-resistant epileptic encephalopathy and lissencephaly underwent VNS. Clinical signs of Horner syndrome appeared a few hours later. Our systematic review of the literature collected only three cases of Horner syndrome following VNS surgery out of 178 patients studied (one case report and two retrospective studies included in review). CONCLUSION: We report the fourth case in the literature, a case of permanent Horner.
Publicações recentes
Miller-Dieker Syndrome: Genetic Etiology, Neurocognitive Impact, and Clinical Implications in a Neuronal Migration Disorder.
Malformations of Cortical Development.
Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders.
CEP170 as a novel molecular link between centrosomal function and cerebral cortical development.
Genetic landscape and phenotypic correlations of lissencephaly: prenatal and postnatal insights.
📚 EuropePMC523 artigos no totalmostrando 197
Genetic landscape and phenotypic correlations of lissencephaly: prenatal and postnatal insights.
Brain communicationsBi-allelic variants in NRDC cause a neurodevelopmental disorder characterized by neonatal lethality, microcephaly, and brain abnormalities.
American journal of human geneticsMRI-based spectral analysis of fetal brain gyrification in typical development and in lissencephaly and polymicrogyria.
Scientific reportsRoles of microtubules and LIS1 in dynein transport machinery assembly.
NatureBiophysical modeling of anatomically realistic prenatal cortical folding development.
Research squareNeonatal-onset epileptic encephalopathy with lissencephaly associated with a SCN3A variant: The first case in Korea and literature review.
SeizureSelective Lis1 inactivation disrupts migration and positioning of cortical somatostatin interneurons.
Scientific reportsNeuro-ophthalmic disorders resulting from defects in the gamma tubulin ring complex: a clinically oriented review.
Ophthalmic geneticsBi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders.
American journal of human geneticsCobblestone lissencephaly in the setting of congenital cytomegalovirus infection: A case report and review of the literature.
Clinical neuropathologyThe Baraitser-Winter Cerebrofrontofacial Syndrome Recurrent R196H Variant in Cytoplasmic β-Actin Impairs Its Cellular Polymerization and Stability.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyA rare complication of vagus nerve stimulation surgery: the Horner Syndrome. Case report and systematic review.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyRethinking fetal central nervous system anomalies: predicting central nervous system anomalies with corpus callosum to head circumference and occipitofrontal diameter ratios.
BMC pregnancy and childbirthBiophysical basis for brain folding and misfolding patterns in ferrets and humans.
eLifeCOP9 signalosome and PRMT5 methylosome complexes are essential regulators of Lis1-dynein-based transport.
Cell reportsCompound Heterozygous PNKP Variants Causing Developmental and Epileptic Encephalopathy with Severe Microcephaly: Natural History of Two New Cases and Literature Review.
NeuroSciExpanding genetic and clinical spectra of β-tubulinopathies: A Korean study.
Journal of human geneticsSubcortical band heterotopia: electroclinical, radiological, and prognostic features in adults.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyDiagnosis of Lissencephaly in a Neonate After Antenatal Polyhydramnios and Suspicion of Fetal Esophageal Atresia: A Case Report.
CureusCapturing disease severity in LIS1-lissencephaly reveals proteostasis dysregulation in patient-derived forebrain organoids.
Nature communicationsPearls & Oy-sters: Acute Obstructive Hydrocephalus Co-Occurrence With Vigabatrin-Associated MRI Changes in an Infant With LIS1-Related Classical Lissencephaly.
NeurologyNeuropathological findings of very low-density lipoprotein receptor-related cerebellar hypoplasia in a full-term fetus.
Journal of neuropathology and experimental neurologyA clinical and genotype-phenotype analysis of MACF1 variants.
American journal of human geneticsA case of Baraitser-Winter cerebrofrontofacial syndrome diagnosed by whole-exome sequencing.
Human genome variationOverview and expansion of CEP85L-associated lissencephaly.
European journal of medical geneticsUnderstanding the Molecular Basis of Miller-Dieker Syndrome.
International journal of molecular sciencesPaediatric cranial ultrasound: abnormalities of the brain in term neonates and young infants.
Insights into imagingSpatial Proteomics Reveals Distinct Protein Patterns in Cortical Migration Disorders Caused by LIN28A Overexpression and WNT Activation.
Molecular & cellular proteomics : MCPDomain specific phenotypic expansion associated with variants in MACF1.
medRxiv : the preprint server for health sciencesTracheal Complications Following Prolonged Invasive Ventilation in Tracheostomized Pediatric Patients with Complex Chronic Conditions.
Children (Basel, Switzerland)Multiple steps of dynein activation by Lis1 visualized by cryo-EM.
Nature structural & molecular biologyDeep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review.
BMC medical genomicsIdentification of MACF1 as a causative gene of generalised epilepsy.
Journal of medical geneticsWDR62 controls cortical radial migration and callosal projection of neurons in the developing cerebral cortex.
Neurobiology of diseaseAltered extracellular matrix structure and elevated stiffness in a brain organoid model for disease.
Nature communicationsTwo New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants.
American journal of medical genetics. Part AManatee cognition and behavior: a neurobiological perspective on an unusual constellation of senses and a unique brain.
Frontiers in behavioral neuroscienceCorpus Callosotomy for Atonic Drop Seizures in Bilateral Malformations of Cortical Development: A Systematic Review of Literature.
CureusA Bioinformatic Investigation into a Unique Human FOXM1 Exon Variant and Its Relevance to Gyrencephaly.
Developmental neuroscienceMultidisciplinary approach to reach a foetal diagnosis of Walker-Warburg syndrome: From autopsy to genetics and back.
Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia"Hair-on-end" appearance in thickened cortex in a case of classic lissencephaly due to DCX gene mutation.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyP253 Next-generation phenotyping facilitates the identification of structural brain malformations in rare disorders through computational brain MRI analysis.
Genetics in medicine openThe response to anti-seizure medications and the development of pharmacoresistant epilepsy in malformations of cortical development.
BMC medicineA Novel Variant c.149G>A in CDK5 Gene Causing Lissencephaly Type 7.
Clinical geneticsUnilateral schizencephaly open lip with septo optic dysplasia in adult woman with glaucoma: A rare case.
Radiology case reportsThe fetal neurologist: Strategies to improve training, practice, and clinical care.
Developmental medicine and child neurologyFetal malformations of cortical development: review and clinical guidance.
Brain : a journal of neurologyCatatonia in a Patient With Lissencephaly Treated With ECT: A Case Report and Literature Review.
The journal of ECTTUBGCP2 variants cause lissencephaly spectrum disorders: a case report and literature review.
Frontiers in pediatricsNeonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro.
VirusesImmediate Therapeutic Response to Vigabatrin in Lissencephaly-Related Epileptic Spasms due to TUBA1A R402H Variant.
American journal of medical genetics. Part APt-LIS1 participates nuclear deformation and acrosome formation via regulating Dynein-1 during spermatogenesis in Portunus trituberculatus.
Scientific reportsDoublecortin restricts neuronal branching by regulating tubulin polyglutamylation.
Nature communicationsDNA ligase IV deficiency identified in a patient with hypergonadotropic hypogonadism: a case report.
Journal of pediatric endocrinology & metabolism : JPEMNuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends.
The Journal of cell biologyDab1 expression level controls Reelin-induced PI3K-Akt activation in early GABAergic neurons.
Biochemical and biophysical research communicationsA Novel MACF1 Gene Mutation: Expanding the Fetal and Neonatal Phenotype.
Pediatric neurologyCoexisting Congenital Mesoblastic Nephroma and Lissencephaly: Unique Case Report with Pathological Analysis and Its Clinical Significance.
BiomedicinesDysregulation of mTOR signalling is a converging mechanism in lissencephaly.
NatureBrain malformation, neurodevelopmental disorder and epilepsy in a case of two rare genetic diseases: overlapping phenotype.
NeurogeneticsHeterozygous inversion on chromosome 17 involving PAFAH1B1 detected by whole genome sequencing in a patient suffering from pachygyria.
European journal of medical geneticsCASP2 biallelic truncating variants: a new case supports the link with lissencephaly/pachygyria and expands the clinical spectrum.
European journal of human genetics : EJHGAnatomo-Electro-Clinical Phenotypes in Children With Epilepsy and DYNC1H1 Mutations.
Pediatric neurologyDoublecortin reinforces microtubules to promote growth cone advance in soft environments.
Current biology : CBLissencephaly with subcortical band heterotopia in an East African child: A case report.
Radiology case reportsRing Chromosome 17 Syndrome-A Case Report and Discussion of Diagnostic Methods.
American journal of medical genetics. Part AMorphometric Development of Medial Surface of Cerebrum in Fetal Cadavers.
Turkish neurosurgeryCryo-EM visualizes multiple steps of dynein's activation pathway.
bioRxiv : the preprint server for biologyThe Aggravation of Neuropsychiatric Symptoms in the Offspring of a Korean Family with Intellectual Disability and Developmental Delay Caused by a Novel ARX p.Lys385Ter Variant.
International journal of molecular sciencesA novel missense variant in the RELN gene in sheep with lissencephaly and cerebellar hypoplasia.
Veterinary pathology[Malformations of cortical development: what's new?].
MedicinaWalker-Warburg syndrome: A case report of congenital muscular dystrophy with hydrocephalus.
Radiology case reportsCobblestone lissencephaly (Type II), clinical, and neuroimaging: A case report and literature review.
Radiology case reports[Genetic analysis of a child with pachygyria due to variant of ADGRG1 gen].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticstubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model.
Molecular neurobiologyCharacterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.
NeuropediatricsA Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker-Warburg-like Features.
GenesExploring unsolved cases of lissencephaly spectrum: integrating exome and genome sequencing for higher diagnostic yield.
Journal of human geneticsSonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.
BiomedicinesMultiplex Consanguineous Family Highlights CLASP1 as a Candidate Gene for Lissencephaly.
Neurology. GeneticsRole of Physiotherapy in Pediatric Lissencephaly: A Case Report and Therapeutic Insights.
CureusDCX knockout ferret reveals a neurogenic mechanism in cortical development.
Cell reportsDe novo monoallelic Reelin missense variants cause dominant neuronal migration disorders via a dominant-negative mechanism.
The Journal of clinical investigationLissencephaly and Advanced-Stage Congenital Cytomegalovirus Infection in a Neonate.
CureusClinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.
EpilepsiaAltered thalamocortical tract trajectory growth with undisrupted thalamic parcellation pattern in human lissencephaly brain at mid-gestational stage.
Neurobiology of diseaseGamma-Tubulin 1 (TUBG1) Mutation-Associated Lissencephaly and Microcephaly in an Indian Child: A Rare Case.
CureusLissencephaly caused by a de novo mutation in tubulin TUBA1A: a case report and literature review.
Frontiers in pediatricsPhenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia.
International journal of molecular sciencesTotal callosotomy ameliorates epileptic activity and improves cognitive function in a patient with Miller-Dieker syndrome.
Epilepsy & behavior reportsLissencephaly: presentation of a clinical case of LIS 1 with a diagnosis confirmed by MLPA method and indications for rehabilitation treatment in childhood.
NeurocaseInfantile epileptic spasms syndrome in a child with lissencephaly associated with de novo PAFAH1B1 variant and coincidental CMV infection.
Epilepsy & behavior reportsPRDM16 co-operates with LHX2 to shape the human brain.
Oxford open neuroscienceMolecular mechanism of dynein-dynactin complex assembly by LIS1.
Science (New York, N.Y.)PAEDIATRIC SYMPTOMATIC SEIZURES IN INDIA: UNRAVELLING VARIED ETIOLOGIES AND NEUROIMAGING PATTERNS - A MULTICENTRIC STUDY.
Georgian medical newsDiagnostic utility of exome sequencing followed by research reanalysis in human brain malformations.
Brain communicationsNUDC is critical for rod photoreceptor function, maintenance, and survival.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyDiagnostic work-up in malformations of cortical development.
Developmental medicine and child neurologyClinical analysis of PAFAH1B1 gene variants in pediatric patients with epilepsy.
SeizureExtensive Phenotypic Variability in Syndrome Dysmorphic Facies, Renal Agenesis, Ambiguous Genitalia, Microcephaly, Polydactyly, and Lissencephaly (DREAM-PL): A Case Report Highlighting Diagnostic and Management Challenges.
CureusGenetic blueprint of congenital muscular dystrophies with brain malformations in Egypt: A report of 11 families.
NeurogeneticsA genetic variant in the MAST1 gene is associated with mega-corpus-callosum syndrome with hypoplastic cerebellar vermis, in a fetus.
Molecular genetics & genomic medicineThe people behind the papers - Meng-Han Tsai, Wan-Cian Lin and Jin-Wu Tsai.
Development (Cambridge, England)Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations.
Acta neuropathologicaA lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.
Development (Cambridge, England)Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography.
Brain sciencesLeveraging multiple approaches for the detection of pathogenic deep intronic variants in developmental and epileptic encephalopathies: A case report.
Epilepsia openExpanding association between BICD2 variants and brain malformations and associated lissencephaly.
Clinical and experimental pediatricsBálint syndrome in a patient with drug-resistant epilepsy having underlying X-linked lissencephaly with subcortical band heterotopia/"double cortex" syndrome.
Neurology perspectivesOPTIC NERVE HYPOPLASIA AND BILATERAL PERSISTENT FETAL VASCULATURE DUE TO TUBA1A TUBULINOPATHY.
Retinal cases & brief reportsMonogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.
Prenatal diagnosisAutomatic Quantification of Normal Brain Gyrification Patterns and Changes in Fetuses with Polymicrogyria and Lissencephaly Based on MRI.
AJNR. American journal of neuroradiologyDCX variants in two unrelated Chinese families with subcortical band heterotopia: Two case reports and review of literature.
HeliyonBi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly.
European journal of human genetics : EJHGFurther characterisation of ARX-related disorders in females due to inherited or de novo variants.
Journal of medical geneticsLissencephaly With Cerebellar Hypoplasia Due To a New RELN Mutation.
Pediatric neurologyExacerbated Zika virus-induced neuropathology and microcephaly in fetuses of dengue-immune nonhuman primates.
Science translational medicineHomozygous MFN2 variants causing severe antenatal encephalopathy with clumped mitochondria.
Brain : a journal of neurologyBrain pathology of lissencephaly type 2 with an ISPD pathogenic variant.
Neuropathology and applied neurobiologyThe people behind the papers - Matt Matrongolo and Max Tischfield.
Development (Cambridge, England)[Analysis of ARX gene variant in a child with X-linked lissencephaly with abnormal genitalia].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsFurther characterization of CEP85L-associated lissencephaly type 10: Report of a three-generation family and review of the literature.
American journal of medical genetics. Part AThe Control of Cortical Folding: Multiple Mechanisms, Multiple Models.
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatryLis1 relieves cytoplasmic dynein-1 autoinhibition by acting as a molecular wedge.
Nature structural & molecular biologyLoss of Twist1 and balanced retinoic acid signaling from the meninges causes cortical folding in mice.
Development (Cambridge, England)X-linked neuronal migration disorders: Gender differences and insights for genetic screening.
International journal of developmental neuroscience : the official journal of the International Society for Developmental NeuroscienceAcute Bowel Ischemia in a Premature Neonate with Miller-Dieker Syndrome and Anomalous Right Coronary Artery From the Pulmonary Artery.
Pediatric annalsPrenatal diagnosis of microcephaly with simplified gyral pattern: series of eight cases.
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyLong-term follow-up and novel variant in Suleiman-El-Hattab syndrome: Expanding the genotypic and clinical spectrum of a rare neurodevelopmental disorder.
European journal of medical geneticsNovel homozygous LAMB1 in-frame deletion in a pediatric patient with brain anomalies and cerebrovascular event.
American journal of medical genetics. Part ANovel loss of function mutation in TUBA1A gene compromises tubulin stability and proteostasis causing spastic paraplegia and ataxia.
Frontiers in cellular neuroscienceBilateral cryptophthalmos with overlapping features of Manitoba oculo-tricho-anal (MOTA) syndrome and Fraser syndrome 2.
BMJ case reportsMicrotubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport.
Nature structural & molecular biologyLIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways.
Nature communicationsAnesthetic Management and Bispectral Index in a Child with Miller-Dieker Syndrome: A Case Report.
Children (Basel, Switzerland)Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy - a Genotype/Phenotype Correlation.
Journal of neuromuscular diseasesSchizencephaly diagnosed after an episode of seizure during labor: A case report.
Clinical case reportsPAFAH1B1 Gene Deletion-Associated Classic Lissencephaly and Infantile Spasms.
Neurology IndiaDiagnosis of fetal cortical abnormalities by new reference charts for assessment of sylvian fissure biometry.
Prenatal diagnosisYWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.
Genetics in medicine : official journal of the American College of Medical GeneticsInsights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.
Molecular neurobiologyMAPping tubulin mutations.
Frontiers in cell and developmental biologyA likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome.
American journal of medical genetics. Part AMissed diagnosis of lissencephaly after prenatal diagnosis: A case report.
MedicineModeling congenital brain malformations with brain organoids: a narrative review.
Translational pediatricsLissencephaly with Congenital Hypothyroidism: A Case Report.
JNMA; journal of the Nepal Medical AssociationPrenatal diagnosis of SMPD4 loss - A neurodevelopmental disorder with microcephaly, arthrogryposis and structural brain anomalies.
Prenatal diagnosisStructures of human dynein in complex with the lissencephaly 1 protein, LIS1.
eLifeLissencephaly-1 mutations enhance traumatic brain injury outcomes in Drosophila.
GeneticsMalformation of the Cortical Development Associated with Severe Clusters of Epileptic Seizures.
Veterinary sciencesRanBP9 controls the oligomeric state of CTLH complex assemblies.
The Journal of biological chemistryAutosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in ASPM and WDR62 Genes.
Molecular syndromologyRole of intracortical neuropil growth in the gyrification of the primate cerebral cortex.
Proceedings of the National Academy of Sciences of the United States of AmericaDual Molecular Diagnoses of Recessive Disorders in a Child from Consanguineous Parents: Case Report and Literature Review.
GenesSpectrum of brain malformations in fetuses with mild tubulinopathy.
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyDoublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking.
eLifeFurther expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller-Dieker syndrome.
American journal of medical genetics. Part AHuman SERPINA3 induces neocortical folding and improves cognitive ability in mice.
Cell discoveryHistopathologic Findings Associated with Miller-Dieker Syndrome: An Autopsy Report.
Diseases (Basel, Switzerland)Familial posterior predominant subcortical band heterotopia caused by a CEP85L missense mutation.
SeizureBi-allelic CAMSAP1 variants cause a clinically recognizable neuronal migration disorder.
American journal of human geneticsLis1-dynein drives corona compaction and limits erroneous microtubule attachment at kinetochores.
Journal of cell scienceObsessive-compulsive symptoms in ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome.
Journal of neural transmission (Vienna, Austria : 1996)MiR-582 Down-Regulates Lissencephaly-1 (LIS1) via P-Akt and MMP-2 to Inhibit Cholangiocarcinoma Cell Proliferation and Invasion.
Iranian journal of biotechnologyPrenatal Diagnosis of Lissencephaly Associated with Biallelic Pathologic Variants in the COQ2 Gene.
Acta medica portuguesaAbnormal course of the corticospinal tracts in KIF5C-related encephalopathy.
European journal of medical geneticsImaging of Congenital Malformations of the Brain.
Clinics in perinatologyLIS1 interacts with CLIP170 to promote tumor growth and metastasis via the Cdc42 signaling pathway in salivary gland adenoid cystic carcinoma.
International journal of oncologyNovel frameshift mutation in LIS1 gene is a probable cause of lissencephaly: a case report.
BMC pediatricsFetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations.
Fetal and pediatric pathologyTubulin mutations in human neurodevelopmental disorders.
Seminars in cell & developmental biologyA homozygous loss-of-function variant in BICD2 is associated with lissencephaly and cerebellar hypoplasia.
Journal of human geneticsTubulinopathy Presenting as Developmental and Epileptic Encephalopathy.
Children (Basel, Switzerland)Seizures and EEG characteristics in a cohort of pediatric patients with dystroglycanopathies.
SeizureCatatonic syndrome and Baraitser Winter syndrome: Case report and review of the literature.
European journal of medical geneticsMonoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders.
Brain : a journal of neurologyFetal Brain Development: Regulating Processes and Related Malformations.
Life (Basel, Switzerland)Broadening the phenotypic spectrum of TUBA1A tubulinopathy to syndromic arthrogryposis multiplex congenita.
American journal of medical genetics. Part ALoss of BAF (mSWI/SNF) chromatin-remodeling ATPase Brg1 causes multiple malformations of cortical development in mice.
Human molecular geneticsGeneration of FLAG-tagged Arx knock-in mouse model.
Genesis (New York, N.Y. : 2000)Brain Organization and Human Diseases.
CellsPrenatal diagnosis of Miller-Dieker syndrome/PAFAH1B1-related lissencephaly: Ultrasonography and genetically investigative results.
European journal of obstetrics, gynecology, and reproductive biologyLissencephaly causing refractory neonatal seizures in a term neonate.
BMJ case reportsLack of association of TP73 with amyotrophic lateral sclerosis in a large cohort of cases.
Neurobiology of agingTUBA1A tubulinopathy mutants disrupt neuron morphogenesis and override XMAP215/Stu2 regulation of microtubule dynamics.
eLifeLIS1 and NDEL1 Regulate Axonal Trafficking of Mitochondria in Mature Neurons.
Frontiers in molecular neuroscienceQuantitative Structural Brain Magnetic Resonance Imaging Analyses: Methodological Overview and Application to Rett Syndrome.
Frontiers in neuroscienceA de novo Non-sense Nuclear Factor I B Mutation (p.Tyr290*) Is Responsible for Brain Malformation and Lung Lobulation Defects.
Frontiers in pediatricsPerioperative total intravenous anesthesia in a child with Walker-Warburg syndrome: A case report.
Saudi journal of anaesthesiaLong-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development: A Cohort Study.
NeurologyAmbiguous Genitalia and Lissencephaly in A 46,XY Neonate with a Novel Variant of Aristaless Gene.
Acta endocrinologica (Bucharest, Romania : 2005)Stem cell-based region-specific brain organoids: Novel models to understand neurodevelopmental defects.
Birth defects researchStructural Consequence of Non-Synonymous Single-Nucleotide Variants in the N-Terminal Domain of LIS1.
International journal of molecular sciencesNovel finding of lissencephaly and severe osteopenia in a Chinese patient with SATB2-associated syndrome and a brief review of literature.
American journal of medical genetics. Part A[Genetic and clinical analysis of KIF2A gene variant in a Chinese patient with complex cortical dysplasia and other brain malformations].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsFrameshift mutation S368fs in the gene encoding cytoskeletal β-actin leads to ACTB-associated syndromic thrombocytopenia by impairing actin dynamics.
European journal of cell biologyAbnormalities in Cortical GABAergic Interneurons of the Primary Motor Cortex Caused by Lis1 (Pafah1b1) Mutation Produce a Non-drastic Functional Phenotype.
Frontiers in cell and developmental biologyAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Genetic landscape and phenotypic correlations of lissencephaly: prenatal and postnatal insights.
- Bi-allelic variants in NRDC cause a neurodevelopmental disorder characterized by neonatal lethality, microcephaly, and brain abnormalities.
- Roles of microtubules and LIS1 in dynein transport machinery assembly.
- Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders.
- A rare complication of vagus nerve stimulation surgery: the Horner Syndrome. Case report and systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology· 2026· PMID 41486386mais citado
- Miller-Dieker Syndrome: Genetic Etiology, Neurocognitive Impact, and Clinical Implications in a Neuronal Migration Disorder.
- Malformations of Cortical Development.
- Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders.
- CEP170 as a novel molecular link between centrosomal function and cerebral cortical development.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:48471(Orphanet)
- MONDO:0018838(MONDO)
- GARD:12291(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Artigo Wikipedia(Wikipedia)
- Q1544416(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
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