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)

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene, with apparent lethality in male embryos. However, recent studies indicate that mutations in the MECP2 gene can cause congenital encephalopathy, an Angelman-like phenotype and even nonspecific mental retardation in males. We report on a 10-year-old boy with moderate mental retardation, hypotonia, obesity and gynaecomastia and a de novo 2-bp deletion in the MECP2 gene that resulted in a frameshift and premature stop codon. As some of the clinical features were suggestive of the Prader-Willi syndrome, it might be worthwhile screening for MECP2 mutations in patients with an atypical Prader-Willi phenotype but without the characteristic abnormalities on chromosome 15q. This report contributes to the phenotypic knowledge of male patients with MECP2 mutations. Moreover, this is the first reported male case of a de novo MECP2 mutation.
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PMID:De novo MECP2 frameshift mutation in a boy with moderate mental retardation, obesity and gynaecomastia. 1208 20

Rett syndrome (RTT) is classically defined by meeting certain clinical diagnostic criteria. It affects mostly females, and one possible pathogenic mechanism was considered to involve mitochondrial function. This was based on the finding of ultrastructural alterations in the mitochondria and decreased respiratory chain enzyme activity. However, the principal etiology of RTT has since been found to be mutations in the MECP2 gene, which is located on the X chromosome. Molecular analysis has allowed the phenotype of MECP2 mutations to be broadened beyond RTT to include girls who have mild mental retardation, autism, and an Angelman syndrome phenotype, as well as males with severe encephalopathy. We present a girl with a previously described mutation in the MECP2 gene whose phenotype is of atypical RTT. She presented with hypotonia and developmental delay in infancy without a clear period of normal development. As part of her evaluation for hypotonia, a muscle biopsy and respiratory chain enzyme analysis showed a slight decrease in respiratory chain enzyme activity consistent with previous reports. This report supports broadening the phenotype of patients who should be considered for MECP2 mutation analysis to include cases of developmental delay and hypotonia without evidence of an initial period of normal development. Furthermore, it supports the hypothesis of an underlying secondary defect in energy metabolism contributing to the pathogenesis of RTT.
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PMID:Infantile hypotonia as a presentation of Rett syndrome. 1221 Mar 19

Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder. Rett syndrome occurs almost exclusively in females and for a long time was thought to be an X-linked dominant condition lethal in hemizygous males. Since the discovery of the MECP2 gene as the cause of Rett syndrome in 1999, MECP2 mutations have, however, also been reported in males. These males phenotypically have classical Rett syndrome when the mutation arises as somatic mosaicism or when they have an extra X chromosome. In all other cases, males with MECP2 mutations show diverse phenotypes different from classical Rett syndrome. The spectrum ranges from severe congenital encephalopathy, mental retardation with various neurological symptoms, occasionally in association with psychiatric illness, to mild mental retardation only. We present a 21-year-old male with severe mental retardation, spastic tetraplegia, dystonia, apraxia and neurogenic scoliosis. A history of early hypotonia evolving into severe spasticity, slowing of head growth, breathing irregularities and good visual interactive behaviour were highly suggestive of Rett syndrome. He has a de novo missense mutation in exon 3 of the MECP2 gene (P225L). The clinical spectrum and molecular findings in males with MECP2 mutations are reviewed.
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PMID:Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). 1261 69

Mutations in a gene on the X-chromosome encoding methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome. We examined clinical symptoms of 27 patients with Rett syndrome (aged 2 to 37 years), diagnosed by the criteria of the Rett Syndrome Diagnostic Criteria Work Group. having MECP2 gene mutations. Two novel MECP2 mutations, 119 del AG resulting in amino acid frame-shift 40fs43X and C to G transversion resulting in amino acid change of F157L, were found. All patients had the most important symptoms of this syndrome, including loss of acquired purposeful hand skills followed by stereotyped hand movements. Two patients had mild perinatal abnormalities. Nine showed psychomotor delay or hypotonia before 6 months. Five patients over 4 years old did not have microcephaly. Speech was preserved in five patients. According to the criteria, 18 cases were diagnosed as Rett syndrome variants. Sixteen out of 26 patients over 3 years old were able to walk (61.5%), and 22 had epilepsy (84.6%). Mutations of the 5 patients without microcephaly were R133C, P225R, R255X, R306C and 376fs386X, whereas those of the 5 variants with preserved speech were 34fs123X, R133C, R255X and R270. Common T158M mutation was detected in 4 patients, R255X in 7 and R270X in 4. Patients with the same mutations showed different phenotypes. Patients with R133C and R306C presented a mild phenotype without microcephaly. Of the proposed diagnostic criteria, the following three may not be essential: apparently normal prenatal and perinatal period, apparently normal psychomotor development through the first 6 months, and deceleration of head growth between 5 months and 4 years.
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PMID:[Clinical symptoms of the Rett syndrome patients with MECP2 gene abnormalities]. 1567 58

Assessment of the development of motor function of Rett syndrome (RTT) revealed hypotonia with failure of crawling and disturbance in skillful hand manipulation are shown as early motor signs. Clinical evaluation has revealed the former as postural hypotonia with failure in locomotion and neurophysiological examinations have showed this to be due to hypofunction of the aminergic neurons of the brainstem. The latter signs are considered to indicate dysfunction of the corticospinal tract at higher levels. As the signs appear along with deceleration of head growth, dysfunction of the noradrenergic neuron, which is involved in synaptogenesis in the cerebral cortex, is postulated as the cause. The characteristic stereotyped hand movements appear in early childhood after loss of purposeful hand use and are underlain by rigid hypertonus. Neurophysiological examinations have indicated that these are due to hypofunction of the nigrostriatal (NS) dopamine (DA) neuron. By comparison with animal experimental work the neurohistochemical changes in the substantia nigra of the autopsied brain of RTT suggest a lesion caused by the dysfunction of the pedunculopontine nucleus, induced by dysfunction of the brainstem aminergic neurons which modulate postural tone and locomotion. Hypofunction of the aminergic neurons also cause 'leakage' of atonia into non-REM stages which lead to disturbances in the autonomic nervous system through inhibition of the reflex system. The grade of disturbance of locomotion closely matches the grade in abnormalities of higher cortical function as indicated by the development of meaningful words. The loci of missense mutation of methyl CPG binding domain of MECP 2gene which affect locomotion severely also markedly impaired their effects on the formation of the heterochromatin. Thus, dysfunction of the aminergic neurons of the brainstem which regulate postural tone and locomotion is proposed as the primary lesion.
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PMID:Early motor disturbances in Rett syndrome and its pathophysiological importance. 1618 86

We describe a clinical profile of a male with Rett syndrome who presented initially with significant axial and peripheral hypotonia, head and truncal titubation and global delay. He is non-ambulatory, lost the few words he had learned and gradually developed hand stereotypes, breathing difficulties, seizures, scoliosis and has osteoporosis sleep problems and sludging in his gall bladder. Prior to diagnosis he underwent comprehensive neurological, metabolic and genetic investigations. After his older sister was diagnosed with atypical Rett syndrome; MECP2 mutation studies on him revealed a pathogenic mutation. His mother is a Rett carrier with a skewed inactivation of chromosome X. Clinical signs and symptoms required to meet the criteria for diagnosis of Rett syndrome have gradually evolved over time. This case demonstrates an unusual family history for Rett syndrome and alerts readers to the utility of screening males for Rett syndrome.
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PMID:Clinical profile of a male with Rett syndrome. 1618 90

This paper reviews the early features of Rett syndrome (RTT). The behavioral characteristics of RTT were analyzed retrospectively by taking history and asking about early infancy behaviors. The earliest behavioral characteristics are thought to be autistic features and hypotonia of trunkal muscles. Analysis of sleep-wake rhythm and all-night polysomnography suggested that the initial lesion is serotonergic and noradrenargic hypofunction at brainstem level. Dopaminergic (DA) hypofunction associated with DA receptor supersensitivity follows as the brain matures. Characteristic symptoms developing at specific age ranges are based on the neuronal connections of the brainstem aminergic neurons and DA neurons with the pedunculo-pontine nuclei, projecting to specific cortical areas.
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PMID:Early behavior characteristics and sleep disturbance in Rett syndrome. 1618 96

Rett syndrome is a unique neurodevelopmental disorder, with onset of hypotonia, autistic tendency, and abnormalities of fine finger movements and gross movements of the arms in early infancy. Clinical features include specific age-dependent symptoms. Studies of early and late signs correlated locomotive dysfunction to language disability and stereotypy to regression of higher cortical functions. Studies of sleep parameters revealed early hypofunction of brainstem aminergic neurons and late occurrence of hypofunction of dopaminergic neurons, followed by receptor supersensitivity. The syndrome's pathophysiology suggests that early hypofunction of aminergic neurons interferes with the development of higher neuronal systems. Particular symptoms surface at different ages throughout the natural course of Rett syndrome, with regressional and static periods.
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PMID:Natural history of Rett syndrome. 1622 33

A 20-year-old female with an established diagnosis of Rett syndrome was found dead in bed. There had been no history of recent deterioration in health and at autopsy no acute lesions were found. There was no evidence of trauma. Toxicological analysis of blood revealed therapeutic levels of carbamazepine and clonazepam. Death was attributed to the complications of Rett syndrome, an uncommon developmental disorder characterized by autistic type behaviour, hypotonia, stereotyped movements, seizures and growth failure, caused by mutations in the MECP2 gene on the X chromosome. Establishing the precise cause of sudden death in individuals with Rett syndrome may be difficult as epilepsy, defective autonomic nervous system control and cardiac arrhythmias may relate more to functional problems rather than to defects that can be demonstrated at autopsy. Thus, although there are a variety of well-documented underlying mechanisms that may cause sudden death in this condition, determining the exact sequence of events in an unwitnessed death may be more by inference and elimination, given the absence of pathognomonic and acute lethal lesions that are able to be found histopathologically. 'Complications of Rett syndrome' may, therefore, be the most accurate designation when individuals with this condition are found unexpectedly dead and no anatomical cause of death can be identified at autopsy.
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PMID:Forensic issues and possible mechanisms of sudden death in Rett syndrome. 1626 20

Individuals with Rett syndrome (RS) present a vast array of orthopedic and neurological difficulties. Typical problems, which may need to be addressed, when treating this population are functional limitations, low cardiovascular capacity, hypotonia, ataxia, apraxia, loss of transitional movements, spasticity, scoliosis and/or kyphosis, loss of ambulation, loss of hand function, foot deformities, and spatial disorientation. Coping with such difficulties and overcoming the associated limitations carry a wearisome task for the individual with Rett as well as for her family. An informed and intensely applied physical therapy regime can help the child and the family cope and even overcome the above-mentioned limitations. The present article presents some insights regarding the intervention with individuals with RS, an overview of typical neuromuscular problems associated with RS, and appropriate suggestions pertaining to clinical intervention that have been found to contribute to this population's well-being. The information presented is mainly based on the clinical knowledge of the authors.
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PMID:Physical therapy intervention for individuals with Rett syndrome. 1704 20


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