SEARCH · PubMed Health

Results for “Muscular Atrophy, Spinal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMedDate not supplied

[Changes in the neural conduction in spinal muscular atrophy of the Kennedy type].

Sensory conduction velocity of median and sural nerves was examined in 6 patients with spinal muscular atrophy (SMA) of Kennedy type. In all patients, except the youngest one, slight slowing of sensory conduction velocity and marked decrease of potential amplitude was observed. These changes might suggest that the Kennedy type of SMA differs from another types of SMA and, may be, does not fit into "pure" motoneuron disease.

Adult↗

PubMed1996

Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5.

The survival motor neuron (SMN) gene has been described as a determining gene for spinal muscular atrophy (SMA). SMN has a closely flanking, nearly identical copy (cBCD541). Gene and copy gene can be discriminated by sequence differences in exons 7 and 8. The large majority of SMA patients show homozygous deletions of at least exons 7 and 8 of the SMN gene. A minority of patients show absence of SMN exon 7 but retention of exon 8. This is explained by results of our present analysis of 13 such patients providing evidence for apparent gene-conversion events between SMN and the centromeric copy gene. Instead of applying a separate analysis for absence or presence of SMN exons 7 and 8, we used a contiguous PCR from intron 6 to exon 8. In every case we found a chimeric gene with a fusion of exon 7 of the copy gene and exon 8 of SMN and absence of a normal SMN gene. Similar events, including the fusion counterpart, were observed in a group of controls, although in the presence of a normal SMN gene. Chimeric genes as the result of fusions of parts of SMN and cBCD541 apparently are far from rare and may partly explain the frequently observed SMN deletions in SMA patients.

Chromosomes, Human, Pair 5↗

PubMed1978

Preliminary immunological studies in spinal muscular atrophy.

Evidence of impaired cell-mediated immunity in children with spinal muscular atrophy was obtained using lymphocyte transformation with PHA (20 children) and skin tests with tuberculin and DNCB (35 children). Laryngological examination of 16 children demonstrated hypoplasia of lymphatic tissue in Waldeyer's ring and the cervical lymph nodes. An ectodermal defect involving both spinal cord and thymus is suggested.

Adolescent↗

PubMed1981

Functional classification and orthopaedic management of spinal muscular atrophy.

The majority of patients with chronic infantile and juvenile forms of spinal muscular atrophy survive to adult life. Forty-four patients have been reviewed at an average of 17 years after diagnosis. The subdivision of patients into four groups, based on the maximal physical function developed by the individual, correlates well with the onset and severity of secondary deformity of the limbs and spine. This information allows anticipation of the problems and plans for their treatment to be made from early childhood. After analysis of the orthotic and surgical treatment received by these patients, a specific programme of care is recommended for each of the functional groups.

Adolescent↗

PubMedDate not supplied

Correlation of flexion contractures with upper extremity function and pain for spinal muscular atrophy and congenital myopathy patients.

To ascertain the patients' perception of the consequences of elbow flexion contractures and better understand the circumstances at their inception, we surveyed 405 spinal muscular atrophy and congenital myopathy patients. Diagrams of various elbow angles and questions concerning the effect of elbow contractures on daily activities were part of the survey. Of 108 completed responses, effectively a 24% response rate, 49 reported elbow flexion contractures. Thirteen of the 49 patients reported first noting them during extended periods of inactivity. Elbow flexion contractures greater than 25 degrees were intractable and were reported to hamper 17% (77 of 410) of specifically considered daily activities for the 49 subjects. Twenty-nine of the 49 (59%) subjects with contractures complained of contracture-associated hindrance of at least one daily function. Perceived contracture-associated difficulties increased significantly as a function of contracture severity. Elbow contractures were perceived to be useful by 12% of the respondents. The correlation between contracture severity and upper limb discomfort was also striking. We conclude that elbow flexion contractures are common and perceived to be associated with disability and discomfort for about one-half of spinal muscular atrophy and congenital myopathy patients.

Activities of Daily Living↗

PubMed1985

Hexosaminidase-A deficiency presenting as atypical juvenile-onset spinal muscular atrophy.

Three patients from two families had an unusual phenotypical variant of late-onset hexosaminidase-A deficiency. The clinical picture was dominated by spinal motor neuron involvement mimicking juvenile-onset spinal muscular atrophy. Atypical features included prominent muscle cramps, postural and action tremor, recurrent psychosis, incoordination, corticospinal and corticobulbar involvement, and dysarthria. The presence of these atypical features in patients whose lower motor neuron involvement would otherwise be consistent with juvenile-onset spinal muscular atrophy should raise the suspicion of the presence of hexosaminidase-A deficiency and GM2 gangliosidosis that can be proved by appropriate enzyme assays.

Adult↗

PubMed1998

Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene.

Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMN(T)) gene, although an isolated deletion of SMN(T) exon 8 has never been found. We now report on 2 patients with the typical features of SMA types II and III, who carried a homozygous deletion of SMN(T) exon 8 but retained SMN(T) exon 7. Importantly, to exclude a sequence conversion event of telomeric exon 8, we amplified a fragment that spanned exons 7 and 8 of the SMN gene. The resulting 1,010-base pair (bp) fragments were subjected to nested polymerase chain reaction (PCR) of exon 7. The subsequent restriction analysis failed to show any products of telomeric exon 7, as the site for primer 541C1120 was lost in both alleles. These findings indicate a homozygous deletion of SMN(T) exon 8. Direct sequencing of the cloned 1,010-bp fragment further confirmed that these 2 SMA patients did not possess telomeric exon 8. The more severely affected child also showed a deletion of the neuronal apoptosis inhibitory protein (NAIP) gene. The present findings provide evidence that an isolated deletion of SMN(T) exon 8 is associated with the milder subtypes of SMA. Our data also demonstrate that the additional deletion of the NAIP gene exacerbates the severity of the disease.

Adult↗

PubMed1995

Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases.

Prenatal prediction in families at risk for autosomal recessive proximal spinal muscular atrophy (SMA) mainly of type I is often requested due to the high incidence and the fetal outcome of the disease. So far, only indirect genotype analysis can be performed in SMA families, since the gene has not yet been identified. We present our experience of 109 prenatal diagnoses obtained in 91 families by use of single- and multi-locus polymorphic microsatellites of the region 5q11.2-q13.3. The marker combinations and specific features of the closest microsatellites are described in detail. From 137 requests for prenatal prediction of SMA between October 1991 and August 1994, 28 families were excluded, mostly because the clinical diagnosis was uncertain or doubtful. Others had to be classified as 'SMA-variants' or showed autosomal dominant transmission of SMA. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at high risk (> 99 per cent) of developing the disease, while in seven additional pregnancies no exact prediction could be made due to a recombination event in one parental haplotype. Altogether, recombinations between closely flanking markers were observed in 14 cases. In 35 cases, the parents decided to terminate the pregnancy. Of the remaining pregnancies, 32 could be followed beyond term. All infants were reported to develop normally without signs of SMA. Two children were born with transverse reduction defects of one hand, which was most likely related to early chorionic villus sampling at 9 and 10 weeks' gestation. No further abnormalities could be detected. The limits of indirect genotype analysis and the problems of diagnostic accuracy and heterogeneity of proximal SMA are discussed.

Alleles↗

PubMed1992

Pregnancy and spinal muscular atrophy.

We investigated the course and outcome of pregnancy and its influence on muscle weakness in 12 females with proximal spinal muscular atrophy (SMA) who delivered a total of 17 infants when aged 18-32 years. In 4 females the SMA clearly followed an autosomal recessive mode of inheritance. The disease was autosomal dominantly inherited in 2 patients; the other 6 were sporadic cases. Ages of onset of SMA ranged from 8 months to 29 years; all the females learned to walk, and 10 out of 12 are still ambulatory aged 30-60 years. Pregnancy and delivery were complicated in 10 out of 12 patients by premature labour (4), prolonged labour (3) and delayed postpartum recovery (6). Caesarean section was performed in 3 cases. No deleterious effects on fetal outcome could be detected. Exacerbation of muscle weakness after the second trimester of pregnancy was experienced by 8 females: 5 noticed a persistent deterioration of SMA; in 3 muscle weakness worsened temporarily during pregnancy and was followed by marked improvement in the puerperium. The psychological perceptions, in retrospect, of 10 females concerning their decision to have children were evaluated.

Adult↗

PubMed2004

Joint range of motion limitations in children and young adults with spinal muscular atrophy.

OBJECTIVES: To elicit descriptive data about limited joint range of motion (ROM) in subjects with type II or III spinal muscular atrophy (SMA) and to examine the relation between the number of motions with limited range and both age and functional ability. DESIGN: Descriptive cross-sectional study. SETTING: Neurologic pediatric outpatient clinic at a hospital in Taiwan. PARTICIPANTS: Twenty-seven subjects with SMA type II (mean age, 9.8+/-6.5y) and 17 with SMA type III (mean age, 12.2+/-8.7y). Intervention Measurement with transparent goniometers of joint ROM bilaterally of the shoulder, elbow, wrist, hip, knee, and ankle. MAIN OUTCOME MEASURES: The proportion of participants with each ROM limitation compared with all participants with the same SMA type, age distribution of the participants with each ROM limitation, mean range loss of each motion limitation, and the contracture index (risk index of joint contracture). RESULTS: Eighty-nine percent of the participants with SMA type II experienced knee extension limitation. Approximately 50% of the participants with both types of SMA had ankle dorsiflexion limitation. The motions of knee and hip extension and ankle dorsiflexion also had a relatively high contracture index. The number of motions with limited range positively correlated ( P <.001) with age and upper-extremity functional grade (the higher the functional grade, the poorer the functional ability) for SMA type II. CONCLUSIONS: We found varying degrees of joint ROM limitation. Certain motions were noted to be high risks for the development of contractures. This risk was higher mostly in younger children.

Adolescent↗

PubMed2001

Enuresis and urinary incontinence in children and adolescents with spinal muscular atrophy.

OBJECTIVE: To assess the rate and type of urinary incontinence in a large sample of children and adolescents with spinal muscular atrophy (SMA), a genetic disorder characterized by loss of motor function caused by anterior horn degeneration. PATIENTS, SUBJECTS AND METHODS: The study included 96 severely incapacitated patients with SMA (aged 6.0-18.11 years) who were examined in detail, including a structured interview (Kinder-DIPS), the Child Behaviour Checklist (CBCL) and a specific questionnaire for urinary incontinence. They were compared with two control groups of unaffected siblings and normal children. RESULTS: In all, 29% of the patients were wet at night and/or during the day; mostly younger children with SMA types I and II only were affected. The results of the interview were more reliable than the CBCL. The specific questionnaire revealed a variety of possible functional and neurogenic forms of wetting, including nocturnal enuresis, voiding postponement, dysfunctional voiding, stress, symptomatic (urinary tract infections, UTIs) and neurogenic incontinence. Many patients were constipated, soiled or had UTIs. The rate of behavioural problems was twice as high (32%) as normal (15%; CBCL). CONCLUSION: Children with SMA have a high rate of urinary incontinence which is often overlooked, and not diagnosed and treated adequately. These problems should be addressed routinely by paediatricians in children referred to paediatric urological specialists.

Adolescent↗

PubMed1995

Isolation of microsatellites from the spinal muscular atrophy (SMA) candidate region on chromosome 5q and linkage analysis in Spanish SMA families.

A locus responsible for autosomal recessive spinal muscular atrophy (SMA) on chromosome 5q11.2-q13.3 has been mapped to a critical interval delimited by markers D5S435 and D5S557. By a modification of the Vectorette-(GT)n method, we have isolated three polymorphic CA repeats from two YACs of the SMA region. Two of them (D5S1417 and D5S1416) map within the SMA critical region, and the other (D5S1415) is centromeric to D5S435. Linkage analysis in Spanish SMA families with eleven markers showed that in our families the disease is linked to this region and confirmed that the novel markers are tightly linked to the SMA locus. The most likely order of markers was 5cen-(D5S63/D5S1356)-(D5S125/D5S465)- (D5S435/D5S1417/D5S1416/D5S557)-D5S610- D5S112-D5S127-5qter, with odds against alternative orders > 1,000:1. Genetic distances are in agreement with those previously published. However, the recombination fraction between D5S610 and D5S112 is remarkably greater than expected from the physical distance, suggesting a hot spot for recombination in this region. Our results from haplotype and multipoint analyses show that the SMA locus must lie between D5S465 and D5S112, and lend further support to the current location of the SMA locus.

Base Sequence↗

PubMed2004

In vivo selection reveals combinatorial controls that define a critical exon in the spinal muscular atrophy genes.

Humans have two near identical copies of the survival of motor neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to an inhibitory mutation at position 6 (C6U mutation in transcript) of exon 7. We have recently shown that C6U creates an extended inhibitory context (Exinct) that causes skipping of exon 7 in SMN2. Previous studies have shown that an exonic splicing enhancer associated with Tra2 (Tra2-ESE) is required for exon 7 inclusion in both SMN1 and SMN2. Here we describe the method of in vivo selection that determined the position-specific role of wild-type nucleotides within the entire exon 7. Our results confirmed the existence of Exinct and revealed the presence of an additional inhibitory tract (3'-Cluster) near the 3'-end of exon 7. We also demonstrate that a single nucleotide substitution at the last position of exon 7 improves the 5' splice site (ss) such that the presence of inhibitory elements (Exinct as well as the 3'-Cluster) and the absence of Tra2-ESE no longer determined exon 7 usage. Our results suggest that the evolutionary conserved weak 5' ss may serve as a mechanism to regulate exon 7 splicing under different physiological contexts. This is the first report in which a functional selection method has been applied to analyze the entire exon. This method offers unparallel advantage for determining the relative strength of splice sites, as well as for identifying the novel exonic cis-elements.

Base Sequence↗

PubMed1995

[Pregnancy and delivery in a woman with neuromuscular disease. Spinal muscular atrophy and severely reduced pulmonary function].

Pregnancy and delivery are described in a 22-year-old woman suffering from spinal muscular atrophy. In spite of severe respiratory insufficiency with a vital capacity of 0.6 litre, pregnancy and planned caesarean section in general anaesthesia went without complications. Some explanations for this are presented. Teams involving respiratory centres specialized in the treatment of patients with neuromuscular diseases, obstetricians and neurologists are recommended. These teams may carry out individual counselling, frequent controls, respiratory support and planning of delivery.

Adult↗

PubMed2002

Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1.

Alteration of correct splicing patterns by disruption of an exonic splicing enhancer may be a frequent mechanism by which point mutations cause genetic diseases. Spinal muscular atrophy results from the lack of functional survival of motor neuron 1 gene (SMN1), even though all affected individuals carry a nearly identical, normal SMN2 gene. SMN2 is only partially active because a translationally silent, single-nucleotide difference in exon 7 causes exon skipping. Using ESE motif-prediction tools, mutational analysis and in vivo and in vitro splicing assays, we show that this single-nucleotide change occurs within a heptamer motif of an exonic splicing enhancer, which in SMN1 is recognized directly by SF2/ASF. The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype.

Amino Acid Motifs↗

PubMed1994

Fine mapping of human PI 3-kinase associated p85 alpha transcripts in the YAC contig surrounding the spinal muscular atrophy gene.

During a search for transcribed sequences within the gene region for autosomal recessive spinal muscular atrophy (SMA), two cDNA clones were isolated from a human fetal brain and an adult spinal cord cDNA library, respectively, by use of the cosmid LA96B (LAS96). The clones sized 950 bp and 1733 bp detect a 7.7-kb transcript in all tested human tissues. An additional transcript of 6.6 kb is detectable in brain and kidney, and faintly in skeletal muscle and liver. Using comparative human Northern blot analysis, the isolated LA96B cDNA clones could be identified as parts of the 3' untranslated region from the phosphatidylinositol 3 (PI3)-kinase associated p85 alpha transcripts; these were unknown up to now. The 5' end of the gene was mapped to YAC-EFTA:A, whereas the 3' end was localized within the distal overlapping YAC 85 flanking the SMA candidate gene region.

Adult↗

PubMed2002

Spinal muscular atrophy with progressive myoclonic epilepsy: report of new cases and review of the literature.

Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterised by loss of motor function and muscle atrophy due to anterior horn cell degeneration. The most common variant is chromosome 5-linked proximal SMA, ranging in severity from congenital onset and infantile death to onset in adult life. Genetically separate variants with different distribution of weakness and/or additional features such as central nervous system involvement have been described. A rare variant with associated myoclonic epilepsy and lower motor neuron disease had been previously described in three families before the SMN gene, responsible for the common form of SMA, was isolated. We report four patients from two additional families affected by a syndrome characterised by severe and progressive myoclonic epilepsy and proximal weakness, tremor and lower motor neuron disease proven by electrophysiologic and muscle biopsy findings. Extensive metabolic investigations were normal and genetic analysis excluded the SMN gene. This study confirms that the association of myoclonic epilepsy and motor neuron disease represents a separate clinical and genetic entity from chromosome 5-linked SMA, the primary defect of which remains unknown.

Biopsy↗

PubMed2002

Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy.

We have previously shown that myofibers formed by fusion of muscle satellite cells from spinal muscular atrophy (SMA) I or II undergo degeneration 1 to 3 weeks after innervation by rat embryonic spinal cord explants, whereas normal myofibers survive for several months. In the "muscle component" of the coculture, the only cells responsible for the degeneration are the SMA muscle satellite cells. Moreover, SMA muscle satellite cells do not fuse as rapidly as do normal muscle satellite cells. To determine whether death of muscle cells precedes that of motor neurons, we studied the origin and kinetics of release of apoptotic microparticles. In SMA cocultures, motor neuron apoptosis occurred before myofiber degeneration becomes visible, indicating that SMA myofibers were unable to sustain survival of motor neurons. In normal cocultures, motor neuron apoptosis occurred 4 days after innervation. However, it did not continue beyond 2 days. These results strengthen the hypothesis that SMA is due to a defect in neurotrophic muscle cell function.

Animals↗