An autopsy case of spinal muscular atrophy type III (Kugelberg‐Welander disease)

Kuru, Satoshi; Sakai, Motoko; Konagaya, Masaaki; Yoshida, Mari; Hashizume, Yoshio; Saito, Kayoko

doi:10.1111/j.1440-1789.2008.00910.x

Cited by 62 publications

(57 citation statements)

References 22 publications

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“…Genetic tests to confirm homozygous deletion of SMN1 were performed in 5 patients (4%) and confirmed in 4 [47, 86, 88, 89, 91]. It remains unclear whether this one patient might have had a hemizygous deletion in combination with an intragenic SMN1 point mutation, or ‘non-5q’ SMA [88].…”

Section: Resultsmentioning

confidence: 99%

Cardiac pathology in spinal muscular atrophy: a systematic review

Wijngaarde

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Stam

et al. 2017

Orphanet J Rare Dis

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BackgroundHereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models.MethodsWe systematically reviewed reported cardiac pathology in relation to SMN deficiency. To investigate the relevance of the possible association in more detail, we used clinical classification systems to characterize structural cardiac defects and arrhythmias.ConclusionsSeventy-two studies with a total of 264 SMA patients with reported cardiac pathology were identified, along with 14 publications on SMA mouse models with abnormalities of the heart. Structural cardiac pathology, mainly septal defects and abnormalities of the cardiac outflow tract, was reported predominantly in the most severely affected patients (i.e. SMA type 1). Cardiac rhythm disorders were most frequently reported in patients with milder SMA types (e.g. SMA type 3). All included studies lacked control groups and a standardized approach for cardiac evaluation.The convergence to specific abnormalities of cardiac structure and function may indicate vulnerability of specific cell types or developmental processes relevant for cardiogenesis. Future studies would benefit from a controlled and standardized approach for cardiac evaluation in patients with SMA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0613-5) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Cardiac pathology in spinal muscular atrophy: a systematic review

Wijngaarde

Blank

Stam

et al. 2017

Orphanet J Rare Dis

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“…It is critical that a therapeutic relationship with an experience pulmonary specialist familiar with pediatric neuromuscular disorders is established at the time of initial diagnosis. There is early involvement of the expiratory muscles of ventilation with relative sparing of the diaphragm [34, 35]. In infants with type 1 SMA, the early implementation of noninvansive ventilatory support has been show to improve survival and quality of life [10, 36].…”

Section: Clinical Managementmentioning

confidence: 99%

Spinal Muscular Atrophy

2015

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Incidence The incidence of SMA is 1:11,000 live births [1]. Prevalence The prevalence of the carrier state is approximately 1 in 54 [1]. Severity The clinical severity of SMA correlates inversely with SMN2 gene copy number and varies from an extreme weakness and paraplegia of infancy to a mild proximal weakness of adulthood. Natural History The natural history of SMA is complex and variable. For this reason, clinical subgroups have been defined based upon best motor function attainment during development. Type 1 SMA infants never sit independently. Type 2 SMA children sit at some point during their childhood, but never walk independently. And Type 3 SMA children and adults are able to walk independently at some point in their childhood.

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“…In contrast to ALS, microglia and T‐cells have been mainly overlooked while some reports have highlighted the contributions of astrocytes to disease pathogenesis. More specifically, increased astrogliosis was observed in necropsies of patients74, 75, 76, 77 and in the Smn ∆7 mouse model at both presymptomatic and symptomatic stages 78. SMA patient induced pluripotent stem cell‐derived astrocytes revealed abnormal calcium regulation, decreased glial cell‐derived neurotrophic factor (GDNF) production but normal GLT1 expression 78.…”

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 99%

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

Deguise

Kothary

2017

Ann Clin Transl Neurol

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Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor neuron degeneration, although defects in multiple cell types and tissues have also been implicated. Three independent laboratories recently identified immune organ defects in SMA. We therefore propose a novel pathogenic mechanism contributory to SMA, resulting in higher susceptibility to infection and exacerbated disease progression caused by neuroinflammation. Overall, compromised immune function could significantly affect survival and quality of life of SMA patients. We highlight the recent findings in immune organ defects, their potential consequences on patients, our understanding of neuroinflammation in SMA, and new research hypotheses in SMA pathogenesis.

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An autopsy case of spinal muscular atrophy type III (Kugelberg‐Welander disease)

Cited by 62 publications

References 22 publications

Cardiac pathology in spinal muscular atrophy: a systematic review

Cardiac pathology in spinal muscular atrophy: a systematic review

Spinal Muscular Atrophy

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

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