Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin

Abstract Desminopathy is a genetically heterogeneous disorder with autosomal dominant pattern of inheritance in most affected families; the age of disease onset is on average 30 years. We studied a patient with a history of recurrent episodes of syncope from infancy who later developed second-degree...

Full description

Saved in:
Bibliographic Details
Published in:Neuromuscular disorders : NMD 2009-06, Vol.19 (6), p.418-422
Main Authors: Piñol-Ripoll, Gerard, Shatunov, Alexey, Cabello, Ana, Larrodé, Pilar, de la Puerta, Iris, Pelegrín, Juana, Ramos, Feliciano J, Olivé, Montse, Goldfarb, Lev G
Format: Article
Language:English
Subjects:
Age of Onset
Autosomal recessive inheritance
Cardiomyopathies - genetics
Cardiomyopathies - pathology
Cardiomyopathies - therapy
Defibrillators, Implantable
Desmin - genetics
Desmin mutation
DNA Mutational Analysis
Electrocardiography
Female
Heart - physiopathology
Heart failure
Homozygote
Humans
Infant
Muscles - pathology
Muscles - ultrastructure
Neurology
Restrictive cardiomyopathy
Sequence Deletion
Skeletal myopathy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Desminopathy is a genetically heterogeneous disorder with autosomal dominant pattern of inheritance in most affected families; the age of disease onset is on average 30 years. We studied a patient with a history of recurrent episodes of syncope from infancy who later developed second-degree AV block and restrictive cardiomyopathy; she subsequently suffered several episodes of ventricular tachyarrhythmia requiring implantation of bicameral defibrillator. Neurological examination revealed rapidly progressive bilateral facial weakness, winging of the scapulae, symmetric weakness and atrophy of the trunk muscles, shoulder girdle and distal muscles of both upper and lower extremities. Muscle biopsy demonstrated signs of myofibrillar myopathy with prominent subsarcolemmal desmin-reactive aggregates. Molecular analysis identified a homozygous deletion in DES resulting in a predicted in-frame obliteration of seven amino acids (p.R173_E179del) in the 1B domain of desmin. We describe the youngest known desminopathy patient with severe cardiomyopathy and aggressive course leading to the devastation of cardiac, skeletal and smooth musculature at an early age.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2009.04.004