De novo LMNA mutations cause a new form of congenital muscular dystrophy

Susana Quijano-Roy, Blaise Mbieleu, Carsten G. Bönnemann, Pierre Yves Jeannet, Jaume Colomer, Nigel F. Clarke, Jean Marie Cuisset, Helen Roper, Linda De Meirleir, Adele D'Amico, Rabah Ben Yaou, Andrés Nascimento, Annie Barois, Laurence Demay, Enrico Bertini, Ana Ferreiro, Caroline A. Sewry, Norma B. Romero, Monique Ryan, Francesco MuntoniPascale Guicheney, Pascale Richard, Gisèle Bonne, Brigitte Estournet

Research output: Contribution to journalArticlepeer-review


Objective: To describe a new entity of congenital muscular dystrophies caused by de novo LMNA mutations. Methods: Fifteen patients presenting with a myopathy of onset in the first year of life were subjected to neurological and genetic evaluation. Histopathological and immunohistochemical analyses were performed for all patients. Results: The 15 patients presented with muscle weakness in the first year of life, and all had de novo heterozygous LMNA mutations. Three of them had severe early-onset disease, no motor development, and the rest experienced development of a "dropped head" syndrome phenotype. Despite variable severity, there was a consistent clinical pattern. Patients typically presented with selective axial weakness and wasting of the cervicoaxial muscles. Limb involvement was predominantly proximal in upper extremities and distal in lower extremities. Talipes feet and a rigid spine with thoracic lordosis developed early. Proximal contractures appeared later, most often in lower limbs, sparing the elbows. Ten children required ventilatory support, three continuously through tracheotomy. Cardiac arrhythmias were observed in four of the oldest patients but were symptomatic only in one. Creatine kinase levels were mild to moderately increased. Muscle biopsies showed dystrophic changes in nine children and nonspecific myopathic changes in the remaining. Markedly atrophic fibers were common, most often type 1, and a few patients showed positive inflammatory markers. Interpretation: The LMNA mutations identified appear to correlate with a relatively severe phenotype. Our results further broaden the spectrum of laminopathies and define a new disease entity that we suggest is best classified as a congenital muscular dystrophy (LMNA-related congenital muscular dystrophy, or L-CMD).

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalAnnals of Neurology
Issue number2
Publication statusPublished - Aug 2008

ASJC Scopus subject areas

  • Neuroscience(all)


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