[Chronic progressive external ophthalmoplegia, deafness, neurogenic muscular atrophy and hypergonadotropic hypogonadism (author's transl)].
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Results for “PROGRESSIVE MUSCULAR ATROPHY”
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[Endocrinological investigation in patients with progressive proximal spinal and bulbar muscular atrophy of late onset (Kennedy-Alter-Sung type) (author's transl)].
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Adult↗
[Problems in weaning from artificial ventilation: 'motor neuron disease'].
Three patients, two men aged 71 and one aged 73 years, were given artificial respiration because of acute respiratory failure. Subsequently they could not be weaned from artificial respiration, due to causes that were not immediately clear. It was ultimately found that the patients suffered from 'motor neuron disease', in two of them due to progressive spinal muscular atrophy, while the third, apart from loss of anterior horn motor cells, also had thoracic hydromelia. The patients died after termination of the artificial respiration.
Aged↗
[Adult form of GM2-gangliosidosis: a man and 2 sisters with hexosaminidase-A and -B deficiency (Sandhoff disease) and literature review].
Three adult siblings had atypical progressive spinal muscular atrophy of the limb-girdle type, predominantly sensory polyneuropathy and cerebellar ataxia. Hexosaminidase A and B activity was profoundly decreased in serum, leukocytes and cultured fibroblasts. GM2-gangliosidosis, variant O (Sandhoff disease) was diagnosed. Mechano-allodynia was the presenting symptom in two of the patients. After 50 years of disease evolution, the patients led an independent life and were intellectually normal. The literature on the adult form of GM2-gangliosidosis is reviewed.
Aged↗
[Neuropsychiatric approach to a child with spinal muscular atrophy. A study of relational problems].
Various years' experience of an extensive series of children suffering from progressive chronic spinal muscular atrophy have made it possible to elaborate a neuropsychiatric approach model conducted on the basis of a viewpoint capable of integrating the clinico-medical aspect and aptitude to empathic listening aimed at establishing a therapeutic alliance with the patient. With advancing age and the course of the disease, in most cases very different difficulties and problems are encountered. These change continuously in relation to the stage reached in emotional development. Entry to school and socialisation mark a particular moment in the confrontation with peers and present the ill child with his diversity. With the emergence of adolescent problems, there is also a dramatic new impact between the body image of a wounded, deteriorated self and the evolutionary effort aimed at identifying with the peer group, the autonomisation of parental figures, the integration of a sexed image of the self. Room can be found in this framework for the child neuropsychiatrist who is able to offer himself as a point of reference and set himself up as a model for elaborating disease anxieties. From personal experience it also emerges that in children suffering from a chronic, often fatal disease there is often the need for a physician to coordinate and integrate needs of both a clinical and sociorelational nature for the purpose of allowing the family to get closer to the needs of their child and prevent him from falling prey to destructive type anxieties.
Child↗
Juvenile muscular atrophy of distal upper extremity (Hirayama disease): focal cervical ischemic poliomyelopathy.
Hirayama disease is characterized by an initially progressive muscular weakness and atrophy of the distal upper limb(s) in adolescence, occurring predominantly in males, followed by spontaneous arrest within several years. Although the disease could be separated from motor neuron disease, some authors considered the illness to be a variant of degenerative motor neuron disease until the first autopsy case was reported which showed focal ischemic changes in the anterior horn of the lower cervical cord. Since then, many in Japan have recognized the disease as cervical ischemic poliomyelopathy; however, several authors in foreign countries did not or do not appreciate the pathologic findings of the disease, and still consider the illness a degenerative motor neuron disease. The pathology of the disease prompted neuroradiologic investigations, which have revealed dynamic changes of the cervical dural sac and spinal cord induced by neck flexion. The cause of these dynamic changes is unknown. However, as the number of patients is exceedingly large in Japan, there may be an ethnic factor.
Adolescent↗
Cloning and characterization of rat neuronal apoptosis inhibitory protein cDNA.
The human neuronal apoptosis inhibitory protein (NAIP) gene was originally discovered because of its deletion in infantile spinal muscular atrophy (SMA), a childhood genetic disorder characterized by motor neuron loss and progressive paralysis with muscular atrophy. Although SMA is now known to be caused by deletions of survival motor neuron (SMN), the fact that NAIP is an anti-apoptotic protein is consistent with the NAIP gene modifying SMA severity. Here we report the cloning of a 1.5 kb rat NAIP cDNA fragment which contains BIR-3 (third baculovirus inhibitory repeat) domain. This fragment shows 78% homology to the human NAIP and 86% homology to the murine counterpart. We have investigated the distribution of NAIP mRNA expressing neurons by in situ RT-PCR technique in the rat central nervous system (CNS). Although all of the neurons appeared to express NAIP mRNA ubiquitously, pronounced elevation of NAIP mRNA expression was observed in the areas innervated by glutamatergic neurons after kainic acid (KA) injection. We have raised an anti-rat NAIP antiserum in rabbits using NAIP cDNA and recombinant rat NAIP, and carried out an immunohistological investigation. We observed highly immunoreactive neuronal subpopulations in the retinal ganglion, cerebral cortex, hippocampus, basal forebrain, thalamus, areas of midbrain, Purkinje cells of the cerebellum, and motor neurons in the spinal cord. Increased immunoreactivity of glutamatergic neurons was also observed broadly in the CNS after KA treatment. This study provides additional evidence that expression of mRNA and gene products of NAIP seem to be regulated in response to excessive stimuli or injuries in rat CNS, and these results are compatible with an anti-apoptotic role of NAIP in acute SMA as well as in brain injuries.
Amino Acid Sequence↗
Autosomal dominant familial spinal and bulbar muscular atrophy with gynecomastia.
The proband, a 53-year-old man, developed progressive spinal and bulbar muscular atrophy and gynecomastia at the age of 50. His father had weakness of lower limbs, and his son had a nasal voice, ocular movement abnormalities, and gynecomastia, whereas two of the proband's brothers showed either gynecomastia or tongue fasciculations. None of the patients showed any expansion of CAG repeat in the androgen receptor gene or any hormonal abnormality. Thus, this family is affected by a form of autosomal dominant spinal and bulbar muscular atrophy with gynecomastia.
Chromosome Aberrations↗
The Hammersmith functional motor scale for children with spinal muscular atrophy: a scale to test ability and monitor progress in children with limited ambulation.
A functional motor scale was devised for use in children with spinal muscular atrophy type 2 and type 3, in particular those with limited mobility, to give objective information on motor ability and clinical progression. The scale, which has 20 scored activities, was designed to be self-explanatory, quick, easy to use, reproducible and reliable. In this paper we describe the development of the scale, reporting the criteria used to choose the items to be included, their application in a normal cohort and in a cohort of children with SMA and how we arrived to a final version of the scale in which the items are arranged in order of difficulty. The analysis of 120 assessments over 2 years from 51 children with type 2 and type 3 SMA also led to a more accurate profile of functional achievements in both type 2 and 3 SMA and to a more detailed sub-classification of type 2 SMA.
Adolescent↗
Progressive myoclonic epilepsy, nerve deafness and spinal muscular atrophy.
A boy of Finnish descent developed nerve deafness at six years of age, action myoclonus two years later, generalized myoclonic seizures when 16 years old and muscular atrophy at the age of 17 years. Bulbar palsy caused his death from inhalational pneumonia when he was 19 years old. Autopsy disclosed no significant changes in the cerebral cortex, thalamus, striatum, Purkinje cells or dentate nucleus. The most striking histological finding was degeneration of motor neurones in cranial nerves and anterior horns of the spinal cord, with neuroaxonal dystrophy of nucleus gracilis and cuneatus. While nerve deafness and spinal muscular atrophy have been recorded (each in different families) in association with progressive myoclonic epilepsy, the combination of these features has not previously been reported. Reasons are put forward for regarding all the system degenerations found in PME, including Unverricht-Lundborg disease (Baltic myoclonus) and the Ramsay Hunt syndrome, as variations of the same disorder.
Adult↗
Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3.
The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, 'hereditary motor and autonomic neuronopathy', and attribute the term, 'survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.
Chromosome Mapping↗
Identification and characterization of a spinal muscular atrophy-determining gene.
Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder characterized by degeneration of lower motor neurons, leading to progressive paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome 5q13, where large-scale deletions have been reported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is either lacking or interrupted in 226 of 229 patients, and patients retaining this gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.
Amino Acid Sequence↗
A rapidly progressive autosomal dominant scapulohumeral form of spinal muscular atrophy.
Three patients from a large pedigree are described who had autosomal dominant spinal muscular atrophy that became manifest between the end of the fourth and the sixth decade. The disease progressed rapidly without evidence of corticospinal tract dysfunction, and within 3 years the patients died from respiratory failure.
Adult↗
[An autopsy case with lower motor neuron disease showing a transient-appearance of anti-GM1 antibody and an improvement of conduction block after gamma-globulin administration].
We report a 63-year-old man who died of respiratory failure. He was well until 1992 (57 years of his age), when he had an onset of progressive weakness of the bilateral upper limbs. He showed no improvement with TRH administration in other hospital. On January 12, 1994, he admitted to our department because of the progressive muscle weakness. Neurologic examination revealed a muscular atrophy associated with severe weakness and hyporeflexia in both upper limbs, and fasciculation were seen in his tongue. Electrophysiological studies revealed mild conduction block in the left medial nerve, and F-waves were not evoked in the left ulnar nerve and bilateral median nerves. After an administration of 25 g/day of human gamma-immunoglobulin for 5 days, conduction block as well as F-wave abnormalities in the left median and left ulnar nerve were improved, yet no improvement of muscle weakness was seen. The anti-GM1 IgG titer was transiently elevated in the patient's serum after gamma-immunoglobulin therapy. On September 8, 1994, subtotal gastrectomy was performed because of the early stage gastric cancer. Histological examination showed poorly differentiated adenocarcinoma (signet-ring cell carcinoma). His muscle weakness had been gradually extended to the lower limbs and he couldn't walk himself on January, 1998. On March, 1998, he developed tetraplegia, mild dysphagia, dysuria and the respiratory disturbance. On April 12, 1998, he admitted to our department for the second time. Neurologic examination revealed a muscular atrophy and fasciculation associated with severe weakness in all of his limbs, tongue and musclus masseter. Neither deep tendon reflex nor pathologic reflex was evoked in his upper and lower extremities. His ocular movements and sensations were well preserved. He died of respiratory failure on May 1, 1998. The patient was presented in a neurological CPC. Neurological and laboratory findings suggested a spinal progressive muscular atrophy (SPMA). However, there were several unusual points as a typical SPMA in this case, that is, an improvement of the electrophysiological abnormalities by gamma-globulin treatment, as well as transient elevation of anti-GM1 antibody. The clinical neurologists have arrived at the conclusion that the patient had lower motor neuron syndrome associated with anti-ganglioside antibody and cause of death was ascribed to the respiratory failure. We discussed whether this case was SPMA or multifocal motor neuropathy. Postmortem examination revealed numerous diverticulums in the ascending colon and lymphothyroiditis. No recurrent carcinoma was detected. Neuropathologically, both severe atrophy of the anterior spinal roots, and severe gliosis and neuronal loss in the anterior horn of the spinal cord were observed. Onuf nuclei were not affected. Neurogenic muscular atrophy was detected in the tongue, diaphragm, and limb muscles. Motor neurons of the brainstem were relatively preserved, but skein-like inclusions as detected by anti-ubiquitin antibody, were present in the facial and hypoglossal nuclei. Neither motor cortex nor cortico-spinal tracts were affected. Demyelination, remyelination or cellular infiltrations were not apparent in the right median nerve and sciatic nerves. The neuropathologic features were compatible with SPMA.
Autoantibodies↗
Molecular genetics of spinal muscular atrophy: contribution of the NAIP gene to clinical severity.
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders characterized by degeneration of anterior horn cells in the spinal cord, and leads to progressive muscular weakness and atrophy. At least three SMA-related genes have been identified: SMN1, NAIP and p44t. We analyzed these genes in 32 SMA patients and found that the SMN1 gene was deleted in 30 of 32 patients (94 %), irrespective of clinical type. The NAIP gene was deleted in 6 patients and its deletion rate was higher in type I patients than that in type U or V. Further, in type I patients lacking the NAIP gene, deterioration in their respiratory function is more rapid than in those type I patients retaining the NAIP gene. Since complete p44t deletion was observed in only 3 patients, the correlation between the p44t deletion and severity of SMA remained ambiguous. We concluded that the NAIP deletion was closely related to the clinical severity of SMA and was a predictive marker of SMA prognosis, while the SMN1 deletion did not correlate with clinical severity.
Adult↗
[Molecular genetic diagnosis and deletion analysis in Type I-III spinal muscular atrophy].
Autosomal recessive spinal muscular atrophy (SMA) is, after cystic fibrosis, the second most common fatal monogenic disorder. The disease is characterized by degeneration of anterior horn cells leading to progressive paralysis with muscular atrophy. Depending on the clinical type (Werdnig-Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III), SMA causes early death or increasing disability in childhood. The SMA-critical region on the long arm of chromosome 5q13.1 contains many duplicated genes and polymorphisms. Recently, two presumptive SMA genes (survival motoneuron gene = SMN, and neuronal apoptosis inhibitory protein = NAIP) have been identified. Deletions involving critical regions of these genes are very often associated with SMA, and the extent of the deletions seems to correlate in part with disease severity. We have evaluated the diagnostic and prognostic value of molecular analysis in a large number of SMA patients. 57 patients and 78 healthy relatives were molecularly screened for deletions in the SMA critical region. We demonstrated homozygous deletions removing the SMN genes in over 90% of patients, whereas nearly 45% of patients exhibited NAIP gene deletions. Large deletions involving both genes on each chromosome are generally found in patients with severe SMA (Werdnig-Hoffman cases), while mildly affected Kugelberg-Welander cases frequently show only deleted SMN genes. Molecular classification based on combined deletion sizes, however, seems not to be exact, especially for the group with chronic SMA (type II and III). Direct DNA testing of patients in whom SMA is suspected is a highly reliable, fast, and noninvasive method. The ability to detect homozygous gene deletions in a high percentage of typical SMA patients will much improve genetic counselling and prenatal diagnosis in affected families.
Adult↗
[A case of spinal muscular atrophy with marked calf hypertrophy and adolescent onset].
We report on a 41-year-old male patient with spinal muscular atrophy (SMA). He had slowly progressive muscular weakness and hypertrophic calves since 14 years of age. The upper arms were slightly, and the thighs moderately atrophic, but the calves were remarkably hypertrophic. There was muscle weakness of both the upper and lower limbs, being more proximal in distribution. He had a positive Gowers' sign and his gait was slightly waddling. Serum creatine kinase level was elevated (518IU/l). Electromyogram revealed a neurogenic pattern. Muscle biopsy of the left biceps brachii showed chronic neurogenic changes. Immunohistochemical examination and Western blot analysis using anti-dystrophin antibodies showed no abnormality. DNA analysis with multiplex PCR proved no deletion in the dystrophin gene, while deletions of exons 7 and 8 of the telomeric copy of survival motor neuron gene were detected. In 1978, Pearn et al. described a new variant syndrome of SMA, characterized by adolescent onset, gross hypertrophy of calves, and a slowly progressive clinical course. The present case is compatible with this syndrome. Therefore, it is suggested that this syndrome, mimicking Becker muscular dystrophy, is not an independent clinical entity, although the phenotype of this syndrome is different from that of typical SMA.
Adolescent↗
Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.
Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior horn cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the same chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.
Adult↗