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Life (Basel, Switzerland) May 2022This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The... (Review)
Review
This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes. We specifically address neural tube defects, holoprosencephaly, malformations of cortical development (including microcephaly, megalencephaly, lissencephaly, cobblestone malformations, gray matter heterotopia, and polymicrogyria), disorders of the corpus callosum, and posterior fossa malformations. Fetal ventriculomegaly, which frequently accompanies these disorders, is also reviewed. Each malformation is described with reference to the etiology, genetic causes, prenatal sonographic imaging, associated anomalies, differential diagnosis, complimentary diagnostic studies, clinical interventions, neurodevelopmental outcome, and life quality.
PubMed: 35743840
DOI: 10.3390/life12060809 -
Orphanet Journal of Rare Diseases Aug 2006Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide... (Review)
Review
Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.
Topics: Abnormalities, Multiple; Brain; Child, Preschool; Dystrophin; Eye Abnormalities; Female; Glycoproteins; Humans; Infant; Infant, Newborn; Mannosyltransferases; Muscular Dystrophies; Mutation; Pregnancy; Prenatal Diagnosis; Prognosis; Syndrome
PubMed: 16887026
DOI: 10.1186/1750-1172-1-29 -
Neurology India 2018
Topics: Abnormalities, Multiple; Brain; Child; Female; Humans; Magnetic Resonance Imaging; Muscular Dystrophies; Walker-Warburg Syndrome
PubMed: 30504606
DOI: 10.4103/0028-3886.246262 -
Frontiers in Bioscience (Scholar... Jan 2010Lissencephaly has been long maintained a malformation involving only the brain. Classic lissencephaly includes agyria and pachygyria and it is the most severe form of... (Review)
Review
Lissencephaly has been long maintained a malformation involving only the brain. Classic lissencephaly includes agyria and pachygyria and it is the most severe form of malformations derived from abnormal neuronal migration. It is defined as a smooth or nearly smooth cerebral surface with absence of normal sulci and gyria. It encompasses a group of syndromes which show many different clinical conditions. Four groups are actually distinguished: classic lissencephaly variants, other lissencephalies including forms with unknown pathogenesis, microlissencephaly spectrum and Cobblestone cortical malformations. Several genes and proteins are involved in this syndromic spectrum and each year new molecular data are reported in the literature: classifications in this sense are always in progress. Lissencephaly now is recognised to involve not only the brain but also several other organs and districts including eyes, face, muscles, genital organs, heart and bones. Mental retardation and different form of epilepsies usually drug-resistant are the main clinical signs. The Authors in this topic discuss on this subject, underlying the different forms of lissencephaly their wide heterogeneity and the complex involvement of several organs.
Topics: Brain; Cell Movement; Cerebral Cortex; Humans; Lissencephaly; Neurons; Syndrome
PubMed: 20036930
DOI: 10.2741/s47 -
The Neurologist May 2008Malformations of cortical development (MCD) are increasingly recognized as an important cause of epilepsy and developmental delay. MCD encompass a wide spectrum of... (Review)
Review
BACKGROUND
Malformations of cortical development (MCD) are increasingly recognized as an important cause of epilepsy and developmental delay. MCD encompass a wide spectrum of disorders with various underlying genetic etiologies and clinical manifestations. High resolution imaging has dramatically improved our recognition of MCD.
REVIEW SUMMARY
This review will provide a brief overview of the stages of normal cortical development, including neuronal proliferation, neuroblast migration, and neuronal organization. Disruptions at various stages lead to characteristic MCD. Disorders of neurogenesis give rise to microcephaly (small brain) or macrocephaly (large brain). Disorders of early neuroblast migration give rise to periventricular heterotopia (neurons located along the ventricles), whereas abnormalities later in migration lead to lissencephaly (smooth brain) or subcortical band heterotopia (smooth brain with a band of heterotopic neurons under the cortex). Abnormal neuronal migration arrest give rise to over migration of neurons in cobblestone lissencephaly. Lastly, disorders of neuronal organization cause polymicrogyria (abnormally small gyri and sulci). This review will also discuss the known genetic mutations and potential mechanisms that contribute to these syndromes.
CONCLUSION
Identification of various gene mutations has not only given us greater insight into some of the pathophysiologic basis of MCD, but also an understanding of the processes involved in normal cortical development.
Topics: Cell Differentiation; Cell Movement; Cerebral Cortex; Genetic Predisposition to Disease; Humans; Mutation; Nervous System Malformations
PubMed: 18469675
DOI: 10.1097/NRL.0b013e31816606b9 -
Frontiers in Neuroscience 2015Neuronal migration disorders are human (or animal) diseases that result from a disruption in the normal movement of neurons from their original birth site to their final... (Review)
Review
Neuronal migration disorders are human (or animal) diseases that result from a disruption in the normal movement of neurons from their original birth site to their final destination during early development. As a consequence, the neurons remain somewhere along their migratory route, their location depending on the pathological mechanism and its severity. The neurons form characteristic abnormalities, which are morphologically classified into several types, such as lissencephaly, heterotopia, and cobblestone dysplasia. Polymicrogyria is classified as a group of malformations that appear secondary to post-migration development; however, recent findings of the underlying molecular mechanisms reveal overlapping processes in the neuronal migration and post-migration development stages. Mutations of many genes are involved in neuronal migration disorders, such as LIS1 and DCX in classical lissencephaly spectrum, TUBA1A in microlissencephaly with agenesis of the corpus callosum, and RELN and VLDLR in lissencephaly with cerebellar hypoplasia. ARX is of particular interest from basic and clinical perspectives because it is critically involved in tangential migration of GABAergic interneurons in the forebrain and its mutations cause a variety of phenotypes ranging from hydranencephaly or lissencephaly to early-onset epileptic encephalopathies, including Ohtahara syndrome and infantile spasms or intellectual disability with no brain malformations. The recent advances in gene and genome analysis technologies will enable the genetic basis of neuronal migration disorders to be unraveled, which, in turn, will facilitate genotype-phenotype correlations to be determined.
PubMed: 26052266
DOI: 10.3389/fnins.2015.00181 -
The Neuroradiology Journal Jun 2015The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the... (Review)
Review
The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies.
Topics: Abnormalities, Multiple; Arachnoid Cysts; Arnold-Chiari Malformation; Cerebellar Diseases; Cerebellum; Cranial Fossa, Posterior; Dandy-Walker Syndrome; Eye Abnormalities; Hamartoma Syndrome, Multiple; Humans; Kidney Diseases, Cystic; Mesencephalon; Retina; Rhombencephalon; Walker-Warburg Syndrome
PubMed: 26246090
DOI: 10.1177/1971400915576665 -
American Journal of Human Genetics Dec 2012Cobblestone lissencephaly is a peculiar brain malformation with characteristic radiological anomalies. It is defined as cortical dysplasia that results when neuroglial...
Cobblestone lissencephaly is a peculiar brain malformation with characteristic radiological anomalies. It is defined as cortical dysplasia that results when neuroglial overmigration into the arachnoid space forms an extracortical layer that produces agyria and/or a "cobblestone" brain surface and ventricular enlargement. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal-recessive diseases characterized by cerebral, ocular, and muscular deficits. These include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama muscular dystrophy. Mutations in POMT1, POMT2, POMGNT1, LARGE, FKTN, and FKRP identified these diseases as alpha-dystroglycanopathies. Our exhaustive screening of these six genes, in a cohort of 90 fetal cases, led to the identification of a mutation in only 53% of the families, suggesting that other genes might also be involved. We therefore decided to perform a genome-wide study in two multiplex families. This allowed us to identify two additional genes: TMEM5 and ISPD. Because TMEM has a glycosyltransferase domain and ISPD has an isoprenoid synthase domain characteristic of nucleotide diP-sugar transferases, these two proteins are thought to be involved in the glycosylation of dystroglycan. Further screening of 40 families with cobblestone lissencephaly identified nonsense and frameshift mutations in another four unrelated cases for each gene, increasing the mutational rate to 64% in our cohort. All these cases displayed a severe phenotype of cobblestone lissencephaly A. TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies.
Topics: Alleles; Cobblestone Lissencephaly; Consanguinity; Exons; Family; Fetus; Gene Order; Genotype; Humans; Introns; Membrane Proteins; Mutation; Nucleotidyltransferases; Pentosyltransferases
PubMed: 23217329
DOI: 10.1016/j.ajhg.2012.10.009