Abstract
Alterations in the LMNA gene cause a wide spectrum of diseases collectively called laminopathies. LMNA-associated congenital muscular dystrophy is a form of laminopathy, which usually
causes infantile onset of muscle weakness, predominantly in the cervical-axial muscles,
and motor developmental retardation. Cardiac symptoms during the first decade of life
are rare. We report a case of LMNA-associated congenital muscular dystrophy in which the patient did not achieve head
control and experienced facial muscle weakness. Cardiac dysrhythmias were observed
at 5 years with development of dilated cardiomyopathy and ischemic strokes at 7 years.
Despite intensive medical intervention, he died suddenly at 9 years. This report broadens
the spectrum of phenotypes of this disorder with the most severe symptoms during the
first decade of life. Our case underscores the need for early genetic testing for
LMNA in patients with congenital muscular dystrophy to screen for cardiac manifestations
and intervene as necessary.
Abbreviations:
CMD (congenital muscular dystrophy), EDMD (Emery–Dreifuss muscular dystrophy), L-CMD (LMNA-associated congenital muscular dystrophy), LGMD1B (limb-girdle muscular dystrophy type 1B), CK (creatine kinase)Keywords
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References
- Gene expression, chromosome position and lamin A/C mutations.Nucleus. 2011; 2: 162-167
- Phenotype-genotype analysis of Chinese patients with early-Onset LMNA-related muscular dystrophy.PLoS ONE. 2015; 10
- LMNA-associated myopathies: the Italian experience in a large cohort of patients.Neurology. 2014; 83: 1634-1644
- De novo LMNA mutations cause a new form of congenital muscular dystrophy.Ann Neurol. 2008; 64: 177-186
- Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy.Neurology. 2012; 78: 1258-1263
- International retrospective natural history study of LMNA-related congenital muscular dystrophy.Brain Commun. 2021; 3: fcab075
- Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death?.J Mol Med (Berl). 2005; 83: 79-83
- Cardiac involvement in patients with lamin A/C gene mutations: a cohort observation.Muscle Nerve. 2012; 46: 187-192
- Importance of early diagnosis in LMNA-related muscular dystrophy for cardiac surveillance.Muscle Nerve. 2019; 60: 668-672
- Surgical treatment of 125 cases of congenital diaphragmatic eventration in a single institution.BMC Surg. 2020; 20: 270
- Neonatal diaphragmatic dysfunction.AJR Am J Roentgenol. 1976; 127: 617-622
- Unilateral elevation of the diaphragm in dystrophia myotonica.Thorax. 1954; 9: 67-70
- Neonatal-onset nemaline myopathy mimicking congenital diaphragmatic hernia.J Pediatr Surg. 2007; 42: e19-e22
- Congenital eventration of the diaphragm: an unusual cause of intractable neonatal respiratory distress with variable etiology.Am J Med Genet. 1987; 27: 213-218
- Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis.Hum Mutat. 2007; 28: 808-815
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.Arch Neurol. 2004; 61: 690
- Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA.Brain Dev. 2017; 39: 361-364
- Nemaline myopathies: a current view.J Muscle Res Cell Motil. 2019; 40: 111-126
- The 2021 version of the gene table of neuromuscular disorders (nuclear genome).Neuromuscul Disord. 2020; 30: 1008-1048
Article info
Publication history
Published online: June 18, 2022
Accepted:
May 23,
2022
Received in revised form:
May 20,
2022
Received:
September 27,
2021
Identification
Copyright
© 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. All rights reserved.
