Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Floppiness/hypotonia is a common neurologic symptom in infancy. A variety of neuromuscular disorders and central nervous system (CNS) disorders cause floppy infant syndrome (FIS). CNS disorders are the much more common causes of the syndrome than neuromuscular disorders. On long-term follow up, cerebral palsy and mental retardation turn out to be the 2 most common causes of FIS. This review focuses on neuromuscular causes of FIS. With the advent of molecular diagnosis, a few conditions can be diagnosed by DNA analysis of the peripheral lymphocytes (myotonic dystrophy, spinal muscular atrophy); however, for the most part, electrodiagnostic studies and muscle biopsy remain as essential diagnostic tools for FIS. Immunohistochemical study of the biopsied muscle also improves diagnostic capability. Management for most conditions remains supportive.
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PMID:Floppy infant syndrome. 1907 54

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission.
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PMID:Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy. 1954 92

We encountered a 53-year-old woman with myotonic dystrophy for a total abdominal hysterectomy. In patients with myotonic dystrophy, hypersensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative management. Combined spinal and epidural block was used in this patient to prevent the occurrence of potential postoperative complications associated with general anesthesia, including respiratory depression. In addition, dexmedetomidine was used for sedation during surgery, because the patient had mental retardation associated with this disease. Airway obstruction was observed after the initial administration of dexmedetomidine at 2 microg x kg(-1) x hr(-1). Therefore, the dose of the drug was reduced to a maintenance dose of 0.2% microg x kg(-1) x hr(-1), resulting in adequate sedation. Dexmedetomidine was proved to be useful in this case; however, use of the drug should be carefully started at a low initial dose in patients with myotonic dystrophy.
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PMID:[Anesthetic management in a case of myotonic distrophy with dexmedetomidine]. 1970 15

Congenital myotonic dystrophy type 1 (CDM1) affects patients from birth and is associated with mental retardation and impaired muscle development. CDM1 patients carry 1000-3000 CTG repeats in the DMPK gene and display defective skeletal muscles differentiation, resulting in reduced size of myotubes and decreased number of satellite cells. In this study, human myoblasts in culture deriving from control and DM1 embryos (3200 CTG repeats) were analyzed using both a biochemical and electron microscopic approach, in order to provide new insights into the molecular mechanisms underlying such alteration. Interestingly, electron microscopy analysis showed not only ultrastructural features of abnormal differentiation but also revealed the presence of autophagic vacuoles in DM1 myoblasts not undergoing differentiation. In accordance with the electron microscopic findings, the autophagic markers LC3 and ATG5, but not apoptotic markers, were significantly up regulated in DM1 myoblasts after differentiating medium addition. The induction of autophagic processes in DM1 myoblasts was concomitant to p53 over-expression and inhibition of the mTOR-S6K1 pathway, causatively involved in autophagy. Moreover biochemical alterations of the two main signal transduction pathways involved in differentiation were observed in DM1 myoblasts, in particular decreased activation of p38MAPK and persistent activation of the MEK-ERK pathway. This work, while demonstrating that major signaling pathways regulating myoblasts differentiation are profoundly deranged in DM1 myoblasts, for the first time provides evidence of autophagy induction, possibly mediated by p53 activation in response to metabolic stress which might contribute to the dystrophic alterations observed in the muscles of congenital DM1 patients.
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PMID:Altered signal transduction pathways and induction of autophagy in human myotonic dystrophy type 1 myoblasts. 2079 47

Not much is known about the neurocognitive deficits in the childhood phenotypic expression of DM1. Twenty-four children and adolescents with no mental retardation were administered an extensive neuropsychological battery to investigate cognition in terms of memory, executive functions and visuo-spatial abilities. The results showed discrepancies between Wechsler's indexes with higher scores in Verbal Comprehension than Perceptive Organization and Speed of Processing. Memory assessment using Signoret's Memory Battery revealed a clear difference between verbal and visuospatial memory but no impairment between short and long-term memory. Concerning executive abilities, DM1 subjects showed greater deficits in processing speed than in mental flexibility, inhibition or working memory. This pattern of deficits could implicate a frontoparietal circuit in accordance with the neural networks involved in the adult form of DM1 and reopens the question of a continuum between childhood and adulthood neurocognitive impairments.
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PMID:A new window on neurocognitive dysfunction in the childhood form of myotonic dystrophy type 1 (DM1). 2159 96

CCG repeats are highly over-represented in exons of the human genome. Usually they are located in the 5' UTR but are also abundant in translated sequences. The CCG repeats are associated with three tri-nucleotide repeat disorders: Huntington's disease, myotonic dystrophy type 1 and chromosome X-linked mental retardation (FRAXE). In this study, we present two crystal structures containing double-stranded CCG repeats: one of an RNA in the native form, and one containing LNA nucleotides. Both duplexes form A-helices but with strands slipped in the 5' (native structure) or the 3' direction (LNA-containing structure). As a result, one of two expected C-C pairs is eliminated from the duplex. Each of the three observed C-C pairs interacts differently, forming either one weak H-bond or none. LNA nucleotides have no apparent effect on the helical parameters but the base stacking is increased compared to the native duplex and the distribution of electrostatic potential in the major groove is changed. The CCG crystal structures explain the thermodynamic fragility of CCG runs and throw light on the observation that the MBNL1 protein recognises CCG runs, as well as CUG and CAG, but not the relatively stable CGG repeats.
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PMID:Crystallographic characterization of CCG repeats. 2271 80

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder with variable expression. DM1 results from a trinucleotide expansion in the 3' untranslated region or the gene for myotonic dystrophy protein kinase (DMPK). Severity tends to increase and it shows a younger onset age with vertical transmission, a phenomenon known as anticipation. Congenital myotonic dystrophy (CDM) is classified as the most severe form of DM1, and its phenotype, with severe hypotonia, neonatal respiratory distress and feeding difficulties, is completely different from that of adult-onset type. Involvement of respiratory muscles may be the major cause of mortality in affected infants. Facial weakness with a tented upper lip is often recognized. If infants survive the neonatal period, muscle involvement symptoms gradually improve and most children do not require respiratory support or tube feeding. As CDM patients grow older, mental retardation or a developmental disorder becomes prominent. Furthermore, the main problems in childhood-onset DM, with an onset age under 10 years, are developmental disorders or learning disabilities, rather than muscle symptoms. Early meticulous support and cooperation with teachers are necessary. Medications such as methylphenidate may be helpful in DM1 children with attention deficit/hyperactivity disorder.
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PMID:[Clinical features and care of patients with congenital and childhood-onset myotonic dystrophy]. 2319 84

Myotonic dystrophy (DM) encompasses two gene defects, DM1 (myotonic dystrophy type 1) being currently the sole disorder leading to a childhood form of the disease. As consequence of the non coding unstable CTG repeat expansion mutation, DM1 presents as an extremely wide and diverse clinical continuum ranging from antenatal to late adult forms, the complexity of the disease being reinforced by multisystemic involvement. The congenital form appears as the most severe end of the phenotypic spectrum and may include marked neonatal hypotonia, respiratory failure, facial diplegia, contractures, and mental retardation. Brain involvement is the hallmark of childhood-onset DM1, distinguished by a normal neonatal period, with learning difficulties as the main presenting symptom, resulting from various degrees of mental delay, psychopathological manifestations, speech defects, hypersomnolence, and fatigue. In contrast, muscle weakness remains usually moderate in childhood, limited to facial weakness, ptosis, and dysarthria, until a decline from the second decade. Orthopedic manifestations including kyphoscoliosis and equinovarus may require surgery. Other organs involvement includes frequent abdominal symptoms, whereas endocrine disturbance is rare. Symptomatic cardiac arrhythmia, mainly exercise-induced, can be observed. While current treatment is mainly symptomatic, future clinical trials are expected following significant progress in pathophysiology and the recent development of molecular therapy approaches.
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PMID:Congenital and infantile myotonic dystrophy. 2362 62

Myotonic dystrophy type 1 (DM-1) is a multi-system disorder affecting the muscles, brain, cardiovascular system, endocrine system, eyes and skin. Diagnosis is made by clinical, electrodiagnostic and genetic studies. This study aimed to determine the correlation between CTG expansion and distribution of muscle weakness and clinical and electrophysiological findings. Genetically confirmed DM-1 patients presenting to Shariati Hospital between 2005 and 2011 were included in this study. Clinical, electrodiagnostic and genetic testing was performed and the correlation between CTG expansion and distribution of muscle weakness and clinical and electromyographic findings was studied. Thirty-three genetically confirmed DM-1 patients were enrolled. Myotonia, bifacial weakness and distal upper limb weakness were seen in all patients. Diabetes mellitus was found in one patient (3%), cardiac disturbance in eight (24.2%), cataracts in eight (24.2%), hypogonadism in five (15.2%), frontal baldness in 13 (39.4%), temporalis wasting in 14 (42.4%), temporomandibular joint disorder in seven (21.2%) and mental retardation in eight (24.2%). The mean number of CTG repeats, measured by Southern blot, was 8780 (range 500-15,833). A negative correlation was found between CTG expansion and age of onset. Temporalis wasting and mental retardation were positively correlated with CTG expansion. No relationship was found between weakness distribution, electromyographic findings, other systemic features and CTG expansion. In this study of DM-1 in Iran, we found a correlation between CTG expansion and age of onset, temporalis wasting and mental disability. No correlation between CTG expansion and electrodiagnostic and other clinical findings were detected.
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PMID:Correlation between distribution of muscle weakness, electrophysiological findings and CTG expansion in myotonic dystrophy. 2441 93

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment.
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PMID:Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies. 2480 43


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