Congenital muscular dystrophy: use of brain MR imaging findings to predict merosin deficiency.

Lamer, S; Carlier, Robert; Pinard, Jean-Marc; Mompoint, D.; Bagard, Christine; Burdairon, Emmanuel; Estournet, B.; Barois, A; Vallée, C.

doi:10.1148/radiology.206.3.9494506

Cited by 38 publications

(9 citation statements)

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“…Other relevant clinical hallmarks of MDC1A include elevated creatine kinase (CK) levels and dystrophic changes (necrosis and regeneration of fibers, chronic inflammation, and fibrosis) recognizable in muscle biopsies of these patients (Tomé et al., ). Diagnostically important features are the complete absence of laminin‐α2 staining evaluated by immunohistochemistry (IHC) performed in muscle or in skin biopsies (Sewry et al., ) using specific antibodies, and typical white matter changes (WMC) in brain detectable by magnetic resonance imaging (MRI; Lamer et al., ). WMC are related with alterations in the brain's water content, due to modifications in the maturation and/or function of the blood–brain barrier, and are detectable after the first six months to one year of life (Menezes et al., ).…”

Section: Introductionmentioning

confidence: 99%

LAMA2gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes

Oliveira

Gruber²,

Cardoso

et al. 2018

Human Mutation

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Congenital muscular dystrophy type 1A (MDC1A) is one of the main subtypes of early-onset muscle disease, caused by disease-associated variants in the laminin-α2 (LAMA2) gene. MDC1A usually presents as a severe neonatal hypotonia and failure to thrive. Muscle weakness compromises normal motor development, leading to the inability to sit unsupported or to walk independently. The phenotype associated with LAMA2 defects has been expanded to include milder and atypical cases, being now collectively known as LAMA2-related muscular dystrophies (LAMA2-MD). Through an international multicenter collaborative effort, 61 new LAMA2 disease-associated variants were identified in 86 patients, representing the largest number of patients and new disease-causing variants in a single report. The collaborative variant collection was supported by the LOVD-powered LAMA2 gene variant database (https://www.LOVD.nl/LAMA2), updated as part of this work. As of December 2017, the database contains 486 unique LAMA2 variants (309 disease-associated), obtained from direct submissions and literature reports. Database content was systematically reviewed and further insights concerning LAMA2-MD are presented. We focus on the impact of missense changes, especially the c.2461A > C (p.Thr821Pro) variant and its association with late-onset LAMA2-MD. Finally, we report diagnostically challenging cases, highlighting the relevance of modern genetic analysis in the characterization of clinically heterogeneous muscle diseases.

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Section: Introductionmentioning

confidence: 99%

LAMA2gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes

Oliveira

Gruber²,

Cardoso

et al. 2018

Human Mutation

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“…Two Class II studies 31,32 and 1 Class III study 33 demonstrated that abnormal findings on brain imaging studies can predict the subtype-specific diagnosis in some cases, especially in merosinopathy (white matter abnormalities) and some dystroglycanopathies (polymicrogyria, white matter lesions, pontine hypoplasia, and subcortical cerebellar cysts).…”

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confidence: 99%

Evidence-based guideline summary: Evaluation, diagnosis, and management of congenital muscular dystrophy

et al. 2015

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Objective: To delineate optimal diagnostic and therapeutic approaches to congenital muscular dystrophy (CMD) through a systematic review and analysis of the currently available literature.Methods: Relevant, peer-reviewed research articles were identified using a literature search of the MEDLINE, EMBASE, and Scopus databases. Diagnostic and therapeutic data from these articles were extracted and analyzed in accordance with the American Academy of Neurology classification of evidence schemes for diagnostic, prognostic, and therapeutic studies. Recommendations were linked to the strength of the evidence, other related literature, and general principles of care.Results: The geographic and ethnic backgrounds, clinical features, brain imaging studies, muscle imaging studies, and muscle biopsies of children with suspected CMD help predict subtype-specific diagnoses. Genetic testing can confirm some subtype-specific diagnoses, but not all causative genes for CMD have been described. Seizures and respiratory complications occur in specific subtypes. There is insufficient evidence to determine the efficacy of various treatment interventions to optimize respiratory, orthopedic, and nutritional outcomes, and more data are needed regarding complications. Recommendations: Multidisciplinary care by experienced teams is important for diagnosing andpromoting the health of children with CMD. Accurate assessment of clinical presentations and genetic data will help in identifying the correct subtype-specific diagnosis in many cases. Multiorgan system complications occur frequently; surveillance and prompt interventions are likely to be beneficial for affected children. More research is needed to fill gaps in knowledge regarding this category of muscular dystrophies. Neurology ® 2015;84:1369-1378 GLOSSARY AAN 5 American Academy of Neurology; AANEM 5 American Association of Neuromuscular & Electrodiagnostic Medicine; B3GALNT2 5 b-1,3-N-acetylgalactosaminyltransferase 2; B3GNT1 5 b-1,3-N-acetylglucosaminyltransferase 1; CK 5 creatine kinase; CMD 5 congenital muscular dystrophy; COL6A1 5 collagen 6a1; COL6A2 5 collagen 6a2; COL6A3 5 collagen 6a3; DAG1 5 a-dystroglycan; FKTN 5 fukutin; GMPPB 5 GDP-mannose pyrophosphorylase B; LAMA2 5 laminin a2; LMNA 5 lamin A/C; MD 5 muscular dystrophy; MDC 5 merosin-deficient congenital muscular dystrophy; SEPN1 5 selenoprotein 1; SGK196 5 protein-O-mannose kinase; TMEM5 5 TMEM5.

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“…In this autosomal‐recessive inherited congenital muscular dystrophy merosin, the α 2 laminin subunit, is mutated and either absent or greatly reduced 68–71 . There has been a milder clinical phenotype with a partial protein defect producing a truncated protein 72,73 .…”

Section: Merosinopathy (Figure 2g–i)mentioning

confidence: 99%

Diagnostic immunohistochemistry in neuromuscular disorders

Tews

Goebel

2005

Histopathology

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Most neuromuscular disorders display only non-specific myopathological features in routine histological preparations. However, a number of proteins, including sarcolemmal, sarcomeric, and nuclear proteins as well as enzymes with defects responsible for neuromuscular disorders, have been identified during the past two decades, allowing a more specific and firm diagnosis of muscle diseases. Identification of protein defects relies predominantly on immunohistochemical preparations and on Western blot analysis. While immunohistochemistry is very useful in identifying abnormal expression of primary protein abnormalities in recessive conditions, it is less helpful in detecting primary defects in dominantly inherited disorders. Abnormal immunohistochemical expression patterns can be confirmed by Western blot analysis which may also be informative in dominant disorders, although its role has yet to be established. Besides identification of specific protein defects, immunohistochemistry is also helpful in the differentiation of inflammatory myopathies by subtyping cellular infiltrates and demonstrating up-regulation of subtle immunological parameters such as cell adhesion molecules. The role of immunohistochemistry in denervating disorders, however, remains controversial in the absence of a reliable marker of muscle fibre denervation. Nevertheless, as well as the diagnostic value of immunocytochemical analysis it may also widen understanding of muscle fibre pathology as well as help in the development of therapeutic strategies.

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Congenital muscular dystrophy: use of brain MR imaging findings to predict merosin deficiency.

Abstract: Diffuse white matter changes resembling those seen with leukodystrophy may be a valuable criterion for diagnosis of merosin deficiency in patients with classic congenital muscular dystrophy.

Cited by 38 publications

References 0 publications

LAMA2gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes

LAMA2gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes

Evidence-based guideline summary: Evaluation, diagnosis, and management of congenital muscular dystrophy

Diagnostic immunohistochemistry in neuromuscular disorders

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