Dilated cardiomyopathy with conduction defects in a patient with partial merosin deficiency due to mutations in the laminin‐α2‐chain gene: A chance association or a novel phenotype?

Carboni, Nicola; Marrosu, Giovanni; Porcu, Maurizio; Mateddu, Anna; Solla, E; Cocco, Eleonora; Maioli, Maria Antonietta; Oppo, Valentina; Piras, Romano; Marrosu, Maria Giovanna

doi:10.1002/mus.22228

Cited by 32 publications

(24 citation statements)

References 6 publications

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“…However, as previously indicated, regular cardiac monitoring is recommended from diagnosis and in particular after the third decade, when more severe cardiac abnormalities and sudden death have been more often described. 9,[40][41][42][43][44][45] While seizures have been reported in up to 30% of LAMA2-RD patients older than six years regardless of LAMA2 expression on muscle biopsy, 46,47 seizures were not common in this cohort of CD patients and absent in PD subjects. Also, no correlation between structural brain changes, epilepsy or learning difficulties were noted in our cohort.…”

Section: Discussionmentioning

confidence: 60%

LAMA2‐related muscular dystrophy: Natural history of a large pediatric cohort

Zambon

Ridout

Main

et al. 2020

Ann Clin Transl Neurol

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Objective: To characterize natural history of Laminin-a2 related muscular dystrophies (LAMA2-RD) to help anticipating complications and identifying reliable outcome measures for clinical trial design and powering. Methods: We conducted a retrospective, single-center, cross-sectional and longitudinal study on 46 LAMA2-RD pediatric patients (37 families). Patients were seen at the Dubowitz Neuromuscular Centre, London between 1985 and 2019. Data were collected by case note reviews. Time-to-event analysis was performed to estimate median age at complications occurrence. Results: Forty two patients had complete deficiency of Laminin-a2 (CD) and four had partial deficiency (PD). Median age at first and last assessment was 2 years and 12.1 years, respectively. Median follow-up length was 7.8 years (range 0-18 years). Seven CD patients died at median age 12 years. One CD and two PD subjects achieved independent ambulation. We observed a linear increase in elbow flexor contractures in CD subjects. Thirty-two CD and one PD patient developed scoliosis, nine underwent spinal surgery. Twenty-two CD required nocturnal noninvasive ventilation (median age 11.7 years). CD subjects showed a 2.9% linear annual decline in forced vital capacity % predicted. Nineteen CD and one PD patient required gastrostomy insertion for failure to thrive and/or unsafe swallow (median age 10.9 years). Four CD patients had partial seizures. Mild left cardiac ventricular dysfunction and rhythm disturbances were identified in seven CD patients. Interpretation: This retrospective longitudinal study provides longterm natural history of LAMA2-RD. This will help management and identification of key milestones of disease progression that could be considered for future therapeutic intervention.

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Section: Discussionmentioning

confidence: 60%

LAMA2‐related muscular dystrophy: Natural history of a large pediatric cohort

Zambon

Ridout

Main

et al. 2020

Ann Clin Transl Neurol

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“…In 2010, Germanyeh et al [11] reported 5 patients with absent laminin α2 staining and cardiac abnormalities including mitral regurgitation, pulmonary hypertension, palpitations and wall motion hypokinesia on echocardiogram (Table 2). More recently, 3 patients (Table 2) have been described with cardiopathy: 2 with dilated cardiomyopathy, one of whom with ventricular arrhythmia [9] and one with impaired left ventricular contractility [34]. All of these reports combined with our patients (Patients #1 and #3) suggest that laminin α2 deficiency may indeed lead to an overt cardiomyopathy.…”

Section: Discussionmentioning

confidence: 58%

Laminin α2 Deficiency-Related Muscular Dystrophy Mimicking Emery-Dreifuss and Collagen VI related Diseases

Nelson

Stojkovic

Allamand

et al. 2015

JND

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Background: Laminin α2 deficient congenital muscular dystrophy, caused by mutations in the LAMA2 gene, is characterized by early muscle weakness associated with abnormal white matter signal on cerebral MRI. Objective: To report on 4 patients with LAMA2 gene mutations whose original clinical features complicated the diagnosis strategy. Methods: Clinical, electrophysiological, muscle imaging and histopathological data were retrospectively collected from all patients. DNA samples were analysed by next-generation sequencing or direct gene sequencing. Laminin α2 was analysed by western-blot and immunohistochemistry. Results: The four patients achieved independent walking. All had proximal muscle weakness with scapular winging and prominent joint contractures without peripheral neuropathy. During follow-up, two patients suffered from refractory epilepsy associated with brain leukoencephalopathy in one, polymicrogyria and lissencephaly without white matter changes in the other. In two patients, the distribution of fatty infiltration resembles that of collagen-VI related myopathies. Dilated cardiomyopathy contstartabstractwith conduction defects, suggestive of Emery-Dreifuss myopathy, emerged in two of them within the 4th decade. Molecular diagnosis remained elusive for many years. Finally, targeted capture-DNA sequencing unveiled the involvement of the LAMA2 gene in two families, and led us to further identify LAMA2 mutations in the remaining family using Sanger sequencing.Conclusions: This report extends the clinical and radiological features of partial Laminin α2 deficiency since patients showed atypical manifestations including dilated cardiomyopathy with conduction defects in 2, epilepsy in 2, one of whom also had sole cortical brain abnormalities. Importantly, clinical findings and muscle imaging initially pointed to collagen-VI related disorders and Emery-Dreifuss muscular dystrophy.

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“…Symptomatic and subclinical cardiac involvement has been previously reported, notably in typical cases with absent laminin-a2 staining [4,6,7]. Regarding partial defects, cardiac involvement was documented only in one patient [8].…”

Section: Introductionmentioning

confidence: 76%

“…To the best of our knowledge, only one case of partial defect of laminin-a2 with cardiac involvement was previously reported [8]. Long-term evaluation led to a diagnosis of dilated cardiomyopathy with ventricular arrhythmias, requiring implantation of an intracardiac defibrillator.…”

Section: Discussionmentioning

confidence: 99%

Atypical phenotype in two patients with LAMA2 mutations

Marques¹,

Duarte

Costa

et al. 2014

Neuromuscular Disorders

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Congenital muscular dystrophy type 1A is caused by mutations in the LAMA2 gene, which encodes the a2-chain of laminin. We report two patients with partial laminin-a2 deficiency and atypical phenotypes, one with almost exclusive central nervous system involvement (cognitive impairment and refractory epilepsy) and the second with marked cardiac dysfunction, rigid spine syndrome and limb-girdle weakness. Patients underwent clinical, histopathological, imaging and genetic studies. Both cases have two heterozygous LAMA2 variants sharing a potentially pathogenic missense mutation c.2461A>C (p.Thr821Pro) located in exon 18. Brain MRI was instrumental for the diagnosis, since muscular examination and motor achievements were normal in the first patient and there was a severe cardiac involvement in the second. The clinical phenotype of the patients is markedly different which could in part be explained by the different combination of mutations types (two missense versus a missense and a truncating mutation).

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Dilated cardiomyopathy with conduction defects in a patient with partial merosin deficiency due to mutations in the laminin‐α2‐chain gene: A chance association or a novel phenotype?

Cited by 32 publications

References 6 publications

LAMA2‐related muscular dystrophy: Natural history of a large pediatric cohort

LAMA2‐related muscular dystrophy: Natural history of a large pediatric cohort

Laminin α2 Deficiency-Related Muscular Dystrophy Mimicking Emery-Dreifuss and Collagen VI related Diseases

Atypical phenotype in two patients with LAMA2 mutations

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