Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital cerebellar ataxia is usually thought to be of cerebellar origin. We report two children with congenital cerebellar ataxia, in whom neuroimaging investigations suggest the possibility of a parietal etiology. The two boys showed hypotonia, delayed motor and cognitive development followed by marked, truncally pronounced ataxia. In one case infantile spasms were treated successfully with adrenocorticotropic hormone, although in follow-up the child suffered from occasional seizures. Magnetic resonance imaging showed in one case parieto-occipital pachygyria and in the other there was marked pachygyria, most pronounced over the parieto-occipital area. In both children cerebellar structures were normal. Cerebello-parietal connections are known to be responsible for acquired parietal limb ataxia. Although not proven, parietal lesions are the most likely etiology of congenital cerebellar ataxia in these two children. Therefore, cerebral, especially parietal pathology must be considered in children with congenital ataxia.
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PMID:Congenital ataxia of parietal origin? Report of two cases. 966 70

We report on 2 families with diffuse pachygyria and cerebellar hypoplasia, who presented hypotonia, ataxia, seizures, and developmental delay since infancy. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed decreased gyral formation in the cerebral cortex and marked hypoplasia in the cerebellum. Cerebellar hypoplasia is often associated with type 2 lissencephaly; however, our cases showed no polymicrogyria, and their clinical findings were quite mild compared with those of microlissencephaly. Their characteristic phenotype suggested a new genetic syndrome, which was possibly inherited as an autosomal recessive trait.
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PMID:Diffuse pachygyria with cerebellar hypoplasia: a milder form of microlissencephaly or a new genetic syndrome? 1051 6

Lissencephaly (agyria-pachygyria) is the most severe neuronal migration disorder, characterized by total or partial absence of gyri. In this study, 21 patients with lissencephaly type I (9 girls, 12 boys) with a mean age of 19 +/- 21 months (2 weeks-8 years) were evaluated clinically and graded according to neuroradiological findings (19 patients by magnetic resonance imaging MRI and 2 by computed tomography CT). Three patients were classified as lissencephaly grade 2 and 18 patients as grade 3 or 4. Clinically, 12 patients (57%) had microcephaly, and eight (38%) had facial dysmorphism. All the patients had prominent psychomotor retardation, moderate to severe; the most frequent neurological findings were spastic guadriplegia (36.4%) and hypotonia with exaggerated tendon reflexes (27.3%). Seventy-eight percent of the patients had epileptic seizures resistant to conventional treatment. Lissencephaly is a cerebral cortical malformation that should be considered in children with developmental delay with or without microcephaly and facial dysmorphism. In addition, it should be investigated in the etiology of early-onset childhood epilepsy.
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PMID:Clinical features of 21 patients with lissencephaly type I (agyria-pachygyria). 1110 19

Neuronal migration disorders of the cerebral cortex form a heterogeneous group of abnormalities, characterised by mental retardation, epilepsy and hypotonia. They are prevalent in 1% of the population and in 20-40% of the untreatable forms of epilepsy. Disorders at the start of the migration result in nodular heterotopias. Bilateral periventricular nodular heterotopias are X-linked disorders, in which cortical neurons are unable to leave their position at the ventricular surface due to the absence of filamin 1. The large group of lissencephalies can be divided into a number of syndromes, each of which is characterised by a gene mutation (LIS1, DCX, RELN). These mutations result in agyria and pachygyria, which are characteristic for this group. A number of these abnormalities, especially the smaller nodular heterotopias and focal cortical dysplasia, may be treated by neurosurgical excision.
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PMID:[Development and developmental disorders of the human brain. III. Neuronal migration disorders of the cerebrum]. 1126 8

Malformations of the cerebral cortex are an important cause of developmental disabilities and epilepsy. Here we review those malformations for which a genetic basis has been elucidated or is suspected and the types of associated epilepsy. Schizencephaly (cleft brain) has a wide anatomo-clinical spectrum, including partial epilepsy in most patients. Familial occurrence is rare. Heterozygous mutations in the EMX2 gene were reported in 13 patients. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in females and prenatal lethality in males. About 88% of patients have partial epilepsy. Filamin A mutations, all leading to a truncated protein, have been reported in three families and in sporadic patients. The most frequent forms of lissencephaly (agyria-pachygyria) are caused by mutations of LIS1. XLIS mutations cause classical lissencephaly in hemizygous males and subcortical band heterotopia (SBH) in heterozygous females. The thickness of the heterotopic band and the degree of pachygyria correlate with the likelihood of developing Lennox-Gastaut syndrome. Mutations of the coding region of XLIS were found in all reported pedigrees and in 38-91% of sporadic female patients with SBH. With few exceptions, children with LIS1 mutations have isolated lissencephaly, with severe developmental delay and infantile spasms. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe developmental delay, seizures, and hypotonia has been associated with mutations of the reelin gene. Fukuyama congenital muscular dystrophy is due to mutations of the fukutin gene and is accompanied by polymicrogyria. Febrile seizures and epilepsy with generalized tonic-convulsions appear in about 50% of children but are usually not severe. Tuberous sclerosis (TS) is caused by mutations in at least two genes, TSC1 and TSC2; 75% of cases are sporadic; 60% of patients have epilepsy, manifested in 50% of them as infantile spasms. TSC1 mutations seem to cause a milder disease with fewer cortical tubers and lower frequency of seizures. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria had familial occurrence on several occasions. Genetic heterogeneity is likely, including autosomal recessive, X-linked dominant, X-linked recessive inheritance, and association with 22q11.2 deletions. About 65% of patients have severe epilepsy, often Lennox-Gastaut syndrome.
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PMID:Epilepsy and genetic malformations of the cerebral cortex. 1157 36

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.
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PMID:X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 1189 29

We reviewed the epileptogenic cortical malformations for which a causative gene has been cloned or a linkage obtained. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in female patients and prenatal lethality in most males. About 90% of patients have focal epilepsy. Filamin A mutations have been reported in all families and in approximately 20% of sporadic patients. A rare recessive form of BPNH also has been reported. Most cases of lissencephaly-pachygyria are caused by mutations of LIS1 and XLIS genes. LIS1 mutations cause a more severe malformation posteriorly. Most children have isolated lissencephaly, with severe developmental delay and infantile spasms, but milder phenotypes have been recorded. XLIS usually causes anteriorly predominant lissencephaly in male patients and subcortical band heterotopia (SBH) in female patients. Thickness of the band and severity of pachygyria correlate with the likelihood of developing Lennox-Gastaut syndrome. Mutations of the coding region of XLIS are found in all reported pedigrees and in 50% of sporadic female patients with SBH. Autosomal recessive lissencephaly with cerebellar hypoplasia; accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the RELN gene. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene need confirmation. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to Xq28 in some pedigrees, autosomal recessive inheritance in others, and association with 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy, often Lennox-Gastaut syndrome. Recessive bilateral frontal polymicrogyria has been linked to chromosome 16q12.2-21.
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PMID:Genetic malformations of the cerebral cortex and epilepsy. 1581 77

Several malformation syndromes with abnormal cortical development have been recognized. Specific causative gene defects and characteristic electroclinical patterns have been identified for some. X-linked periventricular nodular heterotopia is mainly seen in female patients and is often associated with focal epilepsy. FLN1 mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of periventricular nodular heterotopia owing to ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay, and early-onset seizures. Lissencephaly-pachygyria and subcortical band heterotopia represent a malformative spectrum resulting from mutations of either the LIS1 or the DCX (XLIS) gene. LIS1 mutations cause a more severe malformation posteriorly. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior subcortical band heterotopia owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in male patients and subcortical band heterotopia in female patients. Mutations of the coding region of DCX were found in all reported pedigrees and in about 50% of sporadic female patients with subcortical band heterotopia. Mutations of XLIS have also been found in male patients with anterior subcortical band heterotopia and in female patients with normal brain magnetic resonance imaging. The thickness of the band and the severity of pachygyria correlate with the likelihood of developing severe epilepsy. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and infantile spasms with suppression-burst electroencephalograms. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene have not been confirmed. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene.
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PMID:Neuronal migration disorders, genetics, and epileptogenesis. 1592 Dec 28

The malformations of the cerebral cortex represent a major cause of developmental disabilities, severe epilepsy and reproductive disadvantage. The advent of high-resolution MRI techniques has facilitated the in vivo identification of a large group of cortical malformation phenotypes. Several malformation syndromes caused by abnormal cortical development have been recognised and specific causative gene defects have been identified. Periventricular nodular heterotopia (PNH) is a malformation of neuronal migration in which a subset of neurons fails to migrate into the developing cerebral cortex. X-linked PNH is mainly seen in females and is often associated with focal epilepsy. FLNA mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of PNH due ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay and early seizures. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) are disorders of neuronal migration and represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior SBH owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Mutations of DCX have also been found in male patients with anterior SBH and in female relatives with normal brain magnetic resonance imaging. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and seizures with suppression-burst EEG. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. Epilepsy is often present in patients with cortical malformations and tends to be severe, although its incidence and type vary in different malformations. It is estimated that up to 40% of children with drug-resistant epilepsy have a cortical malformation. However, the physiopathological mechanisms relating cortical malformations to epilepsy remain elusive.
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PMID:Genetic malformations of cortical development. 1672 81

Pachygyria is a malformation of the cerebral cortex characterized by an insufficient development of the gyri and cerebral sulci within the anomalies of neuronal migration. Clinically, can cause seizures, mental retardation and motor deficits. We report a rare clinical case of pachygyria in a newborn with persistent hypotonia and sub-clinical seizures in which early diagnosis was possible thanks to cranial magnetic resonance imaging.
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PMID:A case of isolated pachygyria with unusual clinical onset in the neonatal period. 1921 4


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