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

The migrational disorders are a rare group of congenital malformations of the brain. They consist of the following entities--lissencephaly (agyria-pachygyria), pachygyria, schizencephaly, heterotopia and polymicrogyria. We studied 40 children with migrational disorders radiologically with CT and MR. This article (part I) deals with our patients their characteristic CT and MR findings along with their clinical presentation and course. These patients presented with one or a combination of the following symptoms, hypotonia, seizures, failure to thrive, microcephaly and occasionally hydrocephalus. These two groups of migrational disorders have abnormalities affecting the gyral-sulcal pattern of the cortex and gray-white matter distribution of the brain. MR provided better delineation of these disorders than CT. Because some forms of the migrational disorders can be inherited, it is extremely important for the radiologist to understand the characteristic findings for correct diagnosis which is essential for parental counseling.
 ...
PMID:The CT and MR evaluation of migrational disorders of the brain. Part I. Lissencephaly and pachygyria. 271 49

From June. 1987 to Dec. 1988, data was collected from 12 cases with Congenital Brain Anomalies. The cases involved 7 girls and 5 boys with ages ranging from 2 days to 15 years old. Abnormalities diagnosed were Cavum-septi pellucidi; Cavum vergae; Cystic dilated cavum; Cavum veli interpositi; Lissencephaly with dysgenesis of the corpus callosum; Dysgenesis of the corpus callosum associated the midline dorsal cyst; Holoprosencephaly, alobar type; Schizencephaly associated with Hydranencephaly; Encephaloclastic porencephaly; Severe hydrocephalus; Variant type of Dandy-Walker cyst with dysgenesis of the corpus callosum; Arnold-Chiari malformation. The patients were initially seen OPD primarily for seizures and other complaints such as nystagmus with visual impairment, hypotonia, facial anomalies, Yolk-sac tumor, prematurity, dyspnea and hydrocephalus. Among these, Holoprosencephaly was easiest to diagnose because it was combined with facial anomalies. However the others required evaluation by CT. CT offers very efficient diagnostic modality which is better than a Cranial Echo. It is also safer than the invasive angiography and not as expensive as MRI.
 ...
PMID:[Congenital anomalies of the brain in computed tomography]. 276 27

In 1926, Foix, Chavany and Marie described an acquired syndrome of fasciopharyngoglossomasticatory diplegia resulting from bilateral infarction of the anterior operculum. Clinical features consisted of facial diplegia, dysarthria, pseudobulbar palsy, mild to severe mental retardation, and seizures. A developmental form, similar in presentation in adults with MRI findings consisting of bilateral perisylvian cortical malformation consistent with polymicrogyria involving the sylvian fissure and opercular cortex, has been recognized; but few pediatric cases of congenital bilateral perisylvian syndrome (CBPS) have been reported. Over the past four years, we have encountered 12 cases of CBPS presenting in childhood. Age ranges were from 1 week to 11 years with a median of 2.25 years; six were less than two years of age. Seven were male and five female. Ten had bilateral perisylvian polymicrogyria on MRI; two had unilateral perisylvian schizencephaly with contralateral perisylvian polymicrogyria. Clinical manifestations included developmental delay in 7; poor palatal function in 5; hypotonia in 4; arthrogryposis in 4; hemiparesis in 3; apnea in 3; paraparesis in 2; micrognathia in 2; pectus excavatum in 2; quadriparesis in 1; and hearing loss in 1. Seizures occurred in seven (58%) and consisted of infantile spasms (n = 1), generalized tonic-clonic (n = 1), complex partial (n = 2), partial motor (n = 2; 1 with secondary generalization), and febrile convulsions (n = 1). CBPS has different manifestations in the pediatric population than in adults. CBPS is more common than previously thought, is recognizable by MRI and should be suspected clinically in any infant or child presenting with oromotor dysfunction/pseudobulbar signs and developmental delay, especially if there are associated congenital malformations. Epilepsy is not a constant feature in the pediatric presentation and is variable in type and severity.
 ...
PMID:Pediatric congenital bilateral perisylvian syndrome: clinical and MRI features in 12 patients. 930 9

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.
 ...
PMID:Epilepsy and genetic malformations of the cerebral cortex. 1157 36

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.
 ...
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.
 ...
PMID:Neuronal migration disorders, genetics, and epileptogenesis. 1592 Dec 28

We describe 3 patients with bilateral operculum syndrome. They presented with various degrees of suprabulbar (pseudobulbar) signs in addition to delay in cognitive, motor, and speech development in 2 children and developmental language disorder in the third one. A patient with schizencephaly in the left perisylvian area and contralateral polymicrogyria had spastic hemiparesis on the right side, whereas another patient showed bilateral underdevelopment of the opercula in association with axial hypotonia and spastic diplegia. Both of them had epileptiform discharges on the electroencephalogram without clinical manifestations of seizures. The magnetic resonance imaging of the third child with developmental language disorder was normal; however, his electroencephalogram showed frequent bilateral subclinical centrotemporal epileptiform discharges, probably responsible for the speech delay. Structural or functional involvement of the opercula bilaterally was a common finding in all the 3 patients and they had symptoms similar to those described in the developmental type of Foix-Chavany-Marie and Worster-Drought syndromes.
 ...
PMID:Bilateral operculum syndrome in childhood. 1919 75

Schizencephaly is a rare and severe congenital brain defect. Its etiology is not unequivocal and its clinical course differs with every case. The aim of the study was to analyze correlations between clinical and radiologic features of schizencephaly in Polish patients. The study group consisted of 25 children. Epileptic seizures were observed in 60% of cases and in 32% epilepsy was drug resistant. Generalized hypotonia was found in 24%, spastic diparesis in 48%, and spastic hemiparesis in 28% of cases. Seizures were more frequent in the bilateral than unilateral schizencephaly subgroup (72% vs 29%, P = .045). There was a correlation between the presence of the bilateral type II schizencephaly and the occurrence of seizures (P = .002, r = 0.578). There is a correlation between the type of schizencephaly and the presence of seizures in Polish pediatric patients. In most of the patients, schizencephaly leads to developmental retardation and epileptic seizures.
 ...
PMID:Clinical and radiologic features of unilateral and bilateral schizencephaly in polish pediatric patients. 2350 83