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

Détails

ID Serval
serval:BIB_A95FD804D115
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
De novo LMNA mutations cause a new form of congenital muscular dystrophy.
Périodique
Annals of Neurology
Auteur(s)
Quijano-Roy S., Mbieleu B., Bönnemann C.G., Jeannet P.Y., Colomer J., Clarke N.F., Cuisset J.M., Roper H., De Meirleir L., D'Amico A., Ben Yaou R., Nascimento A., Barois A., Demay L., Bertini E., Ferreiro A., Sewry C.A., Romero N.B., Ryan M., Muntoni F., Guicheney P., Richard P., Bonne G., Estournet B.
ISSN
0364-5134
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
64
Numéro
2
Pages
177-186
Langue
anglais
Résumé
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).
Mots-clé
Adult, Child, Child, Preschool, Female, Genetic Markers/genetics, Humans, Lamin Type A/genetics, Male, Muscular Dystrophies, Limb-Girdle/genetics, Muscular Dystrophies, Limb-Girdle/pathology, Mutation/genetics
Pubmed
Web of science
Création de la notice
15/10/2009 8:34
Dernière modification de la notice
03/03/2018 20:22
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