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)

Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.
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PMID:Changing facial phenotype in Cohen syndrome: towards clues for an earlier diagnosis. 2318 44

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
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PMID:[Psychomotor retardation with neutropenia for more than one year in a toddler]. 2997 26

An 11-year-old girl with a history of neutropenia, developmental delay, hypotonia, and intellectual disability was diagnosed with Cohen syndrome after genetic testing discovered homozygous mutation in the VPS13B gene. She was referred to a retinal specialist with a chief complaint of decreased peripheral vision. On examination, decreased visual acuity, pigmentary changes, and nonleaking cystoid macular edema were present in both eyes.
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PMID:Nonleaking cystoid macular edema in Cohen syndrome. 3014 85

Cohen syndrome was initially described as a syndrome including obesity, hypotonia, mental deficiency, and facial, oral, ocular and limb anomalies. Leukopenia, especially neutropenia, was later described as a feature of Cohen syndrome. Cohen syndrome is caused by an autosomal recessive (AR) mutation of the vacuolar protein sorting 13 homolog B (VPS13B, also referred to as COH1) gene on chromosome 8q22.2.
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PMID:Cohen Syndrome: Review of the Literature. 3047 63

Cohen syndrome is a rare autosomal recessive disorder characterized by hypotonia, obesity, developmental delay, mental retardation, and facial, oral, ophthalmic, and limb deformities. Mutations in VPS13B have been found to be responsible for this disorder. In the current report, we have assessed three Iranian families with developmental delay and skeletal deformities. Whole exome sequencing of the affected probands led to identification of the underlying genetic cause in these families. Three mutations were found in VPS13B gene. The detected mutations were c.4608_4609del (p.E1537Rfs*7), c.11486dupG (p.L3830Tfs*13), and c.10360dupC (p.L3454fs*7). The current study broadens the mutation spectrum of VPS13B gene and demonstrates different phenotypic features from classic Cohen syndrome. Moreover, the provided data can be used in genetic counseling and prenatal diagnosis of Iranian patients.
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PMID:Mutations in the VPS13B Gene in Iranian Patients with Different Phenotypes of Cohen Syndrome. 3144 3

Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19-year-old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole-genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene.
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PMID:A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome. 3182 61

Cohen syndrome (CS) is an autosomal recessive congenital disorder, characterized by hypotonia, intellectual disability, developmental delay, microcephaly, progressive retinopathy, neutropenia, truncal obesity, joint laxity, characteristic facial, ophthalmic, oral and appendage abnormalities, and an over friendly behavior. It has been linked to mutations in the VPS13B gene. The main purpose of this study was to determine the genetic cause of CS in an Indian family. Whole exome sequencing (WES) was used to identify the genetic cause of CS in the family. The WES analysis identified a homozygous novel duplication mutation c.5272dupG in the VPS13B gene, leading to formation of a truncating protein. The present study will be advantageous in genetic diagnosis and genetic counseling in CS, and increases the mutational spectrum of this gene.
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PMID:Whole Exome Sequencing Identifies a Novel Homozygous Duplication Mutation in the VPS13B Gene in an Indian Family with Cohen Syndrome. 3217 Jul 14