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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal muscular atrophy is a genetic disorder of the motor neurons that causes profound hypotonia, severe weakness, and often fatal restrictive lung disease. Patients with spinal muscular atrophy present a spectrum of disease from the most severe infantile-onset type, called Werdnig-Hoffmann disease (type 1), associated with a mortality rate of up to 90%, to a late-onset mild form (type 3), wherein patients remain independently ambulatory throughout adult life. Although many clinicians agree that patients with spinal muscular atrophy lose motor abilities with age, it is unknown whether progressive weakness occurs in all patients with spinal muscular atrophy. We present here results of the first prospective study of muscle strength in patients with spinal muscular atrophy. There was no loss in muscle strength as determined by a quantitative muscle test during the observation period. However, motor function diminished dramatically in some patients with spinal muscular atrophy. Explanations for this loss of function could not be determined from our data. Decrease in motor function could be caused by factors other than loss of strength. Therefore, it is not clear from our results whether spinal muscular atrophy is a neurodegenerative disease. We conclude that treatment trials in spinal muscular atrophy should be designed with consideration of the natural history of strength and motor function in this disorder.
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PMID:Prospective analysis of strength in spinal muscular atrophy. DCN/Spinal Muscular Atrophy Group. 1069 94

The classical form of severe spinal muscular atrophy (SMA type 1; Werdnig-Hoffmann disease) has a very consistent clinical phenotype that is well recognized by paediatricians. It usually presents at birth or within the first few months of life. There is general hypotonia, with axial and limb weakness; the legs are affected more than the arms and proximal muscles more than distal, leaving residual spontaneous activity in the feet and in the forearms and hands. Facial muscles are spared so that the infant usually has a bright normal expression. The intercostal muscles are always affected, whereas the diaphragm is spared, allowing adequate spontaneous respiratory activity until the infants are precipitated into respiratory failure by an incidental respiratory infection, or aspiration. With rare exception they die by 2 years of age with a median around 7 months and with about 80% of the children dying by the time they are 1 year old. There is a consistent homozygous deletion in exons 7 and 8 of the telomeric copy of the survival motor neuron (SMN) gene. In the current issue of the journal, MacLeod and her colleagues have documented five cases of more severe spinal muscular atrophy, with a history of diminished fetal movements in utero and presenting at birth with asphyxia and severe weakness.
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PMID:Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. 1070 May 41

We report the association of pontocerebellar hypoplasia and anterior horn cell disease in three female siblings. One child presented with the classical clinical and neuropathological features of pontocerebellar hypoplasia with associated anterior horn cell disease, described by Barth as pontocerebellar hypoplasia type I. This patient showed polyhydramnios, congenital contractures, respiratory insufficiency, hypotonia, areflexia, listlessness and myoclonic seizures. Postmortem examination revealed a loss of neurons and reactive gliosis in the pontocerebellum and in addition anterior horn cell atrophy resembling Werdnig-Hoffmann disease. Another sibling demonstrated the same clinical symptoms. However neuropathological findings showed evidence for pontocerebellar hypoplasia only. The third sibling was examined after induced fetal abortion because of prenatally diagnosed arthrogryposis. Anterior horn cell disease was obvious histologically whereas pontocerebellar hypoplasia could not be demonstrated due to cerebral autolysis. The similar clinical and neuropathological findings in the three reported siblings suggest a common genetic defect with different patterns of pontocerebellar hypoplasia and associated anterior horn cell disease. The gene defect of this rare disorder is still unknown. The 'survival motor neuron' gene of spinal muscular atrophy was not found in these three siblings.
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PMID:Familial pontocerebellar hypoplasia type I with anterior horn cell disease. 1072 90

Congenital hypotonia with favorable outcome is characterized by an early neonatal onset and a benign clinical course. The old term, proposed by Walton, was benign congenital hypotonia, denoting the presence of muscle weakness and hypotonia, with the exception of Werdnig-Hoffmann disease. It has been clear that this term includes congenital myopathies with definite changes in the muscle fiber. However, many cases remain unclarified. The term congenital hypotonia with favorable outcome includes only these last cases. A long-term follow-up study of children with congenital hypotonia with favorable outcome is presented, and a hypothetical mechanism underlying muscle shortening is discussed. The study was carried out at the Department of Child Neuropsychiatric Sciences, University "La Sapienza" of Rome, during the period 1985-2000, and included 41 patients with congenital hypotonia. Our study confirms the good prognosis of congenital hypotonia with favorable outcome and suggests a correlation with joint hyperlaxity, which is observed in many parents of our children, as if the latter developed from the former. On the basis of experimental changes occurring in the muscles, we believe that in our cohort the main cause of shortening is caused by an increase in joint mobility, which keeps muscles shortened in both the passive and active states for a long time. If this view is confirmed by other studies, we suggest continuous muscle exercise as a preventive treatment.
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PMID:Congenital hypotonia with favorable outcome. 1205

Type I spinal muscular atrophy or Werdnig-Hoffman disease is rarely described in black populations. We report five such cases diagnosed in a paediatric outpatient clinic in Dakar. We conducted a retrospective study relating to patients examined for hypotonia progressing since birth for whom the electromyogram had made it possible to confirm an involvement of the peripheral nerve without nerve conduction anomaly. Mean age of diagnosis was 12.3 +/- 7.6 months. Respiratory distress was noted for 2 patients. A family background of similar symptomatology was found in 1 case and consanguinity in 2 cases. Only 1 case of death occurred whereas the 4 other patients were lost to follow-up. The diagnosis of spinal muscular atrophy must be considered in the presence of any severe hypotonia in infants.
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PMID:[Progressive spinal amyotrophy type I or Werdnig-Hoffman disease. Apropos of 5 cases in Dakar (Senegal)]. 1214 64

Pontocerebellar hypoplasia (PCH) is rarely associated with anterior horn cell disease and designated as PCH-1. This phenotype is characterized by severe muscle weakness and hypotonia starting prenatally or at birth with a life span not exceeding a few months in most cases. Milder disease courses with later onset and longer survival are normally not diagnosed as PCH-1. We describe the clinical and neuroradiological findings in nine patients out of six siblingships with evidence of cerebellar defects and early onset spinal muscular atrophy (SMA), representing a broad spectrum of clinical variability. In all patients, the diagnosis of SMA (Werdnig-Hoffmann disease) was made on the basis of electrophysiological data and muscle biopsy; however, genetic testing failed to confirm the diagnosis of infantile SMA with a gene defect on chromosome 5q and resulted in clinical reevaluation. Age at onset was after a normal period in the first months of life in three siblingships and pre- and postnatally in the other three families. Life span was 2-4 years in patients with later onset, and age at death occurred after birth or within months in the more severe group. Two siblingships showed discordant ages at death despite similar treatment. In contrast to the previous definition of PCH-1, our observations suggest the existence of milder phenotypes with pontocerebellar hypoplasia or olivopontocerebellar atrophy in combination with anterior horn cell loss. A pontine involvement is not necessarily seen by neuroimaging methods. The genetic basis of PCH-1 remains to be determined. The gene locus for infantile SMA on chromosome 5q could be excluded by linkage studies. Parental consanguinity and affected siblings make autosomal recessive inheritance most likely.
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PMID:Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. 1254 34

Spinal Muscular Atrophy (SMA) is an autosomal recessive disease characterized by diffuse proximal and distal weakness due to deletions of the survival motor neuron (SMN) gene localised on chromosome 5q13. Pathological studies show decreased numbers of motorneurons in spinal cord. SMA was initially sub-classified clinically into three types base on age at onset and clinical course. SMA type 1, Werdnig-Hoffmann disease, has an onset within the first 6 months and death within the first two years. In contrast, SMA type II has an onset after six months of life and the children achieve the ability to sit unaided. Children with SMA type III (Kugelberg-Welander) usually have normal milestones in the first year and achieve the ability to walk but then show evidence of mild weakness. The prognosis is good and the clinical course is not (or very slowly) progressive. Recently, Dubowitz described a new form of SMA called type 0 with a neonatal onset, facial weakness, progressive and fatal clinical course. These infants show generalised hypotonia, the lower limbs are more affected than the upper with marked weakness of all axial muscles. We report a case of SMA, uncommon for the early onset and the respiratory difficulties. The diagnosis has been done by genetic analyses showing a SMN mutation.
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PMID:[Neonatal muscular spinal atrophy: a case report]. 1570 Jul 40

Werdnig-Hoffmann Disease: Report of the first case clinically identified and genetically confirmed in Central Africa (Kinshasa-Congo): Type 1 spinal muscular atrophy (SMA1) or Werdnig-Hoffman disease is rarely described in black populations. We report on one black patient diagnosed in Kinshasa. This patient was referred to Paediatric consultation at the age of 5 months 1/2 with extreme hypotonia progressing since birth, severe muscular weakness in his trunk and proximal parts of the extremities, ASD type II, and repeated episodes of pulmonary infections. He died of severe respiratory failure at the age of 10 months. EMG analysis revealed motor neuron a defect without nerve conduction anomaly, suggesting the diagnosis of spinal muscular atrophy disease. The diagnosis of SMA1 was definitely confirmed by a quantitative PCR-based testing that demonstrated homozygous deletion of SMN1, the primary disease-causing gene for spinal muscular atrophy, while two normal SMN2 alleles were present. There was a history of similar clinical symptomatology in a patient's older brother, suggesting a familial involvement. To the best of our knowledge, this is the first documented Werdnig-Hoffman case ever reported from Central Africa people.
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PMID:Werdnig-Hoffmann disease: report of the first case clinically identified and genetically confirmed in central Africa (Kinshasa-Congo). 2016 70

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic severity going from high mortality within the first year for SMA type 1 to no mortality for the chronic and later onset forms.
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PMID:Spinal muscular atrophy. 2204 5


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