Abstract
Centronuclear myopathies (CNM) describe a group of rare muscle diseases typically presenting an abnormal positioning of nuclei in muscle fibers. To date, three genes are known to be associated to a classical CNM phenotype. The X-linked neonatal form (XLCNM) is due to mutations in MTM1 and involves a severe and generalized muscle weakness at birth. The autosomal dominant form results from DNM2 mutations and has been described with early childhood and adult onset (ADCNM). Autosomal recessive centronuclear myopathy (ARCNM) is less characterized and has recently been associated to mutations in BIN1, encoding amphiphysin 2. Here we present the first clinical description of intrafamilal variability in two first-degree cousins with a novel BIN1 stop mutation. In addition to skeletal muscle defects, both patients have mild mental retardation and the more severely affected male also displays abnormal ventilation and cardiac arrhythmia, thus expanding the phenotypic spectrum of BIN1-related CNM to non skeletal muscle defects. We provide an up-to-date review of all previous cases with ARCNM and BIN1 mutations.
Highlights
Centronuclear myopathies (CNM) are a group of congenital disorders characterized by hypotonia and skeletal muscle biopsies typically showing small rounded fibers with central nuclei [1,2,3,4]
It is the first time that patients with a BIN1 mutation are analyzed by whole-body MRI and the results contrast previous findings on dynamin 2 (DNM2)-related CNM
Ophtalmoplegia/paresis, as seen in both patients, is not a common sign of Autosomal recessive centronuclear myopathy (ARCNM) (Table 1), while it is consistently reported for the X-linked form
Summary
Centronuclear myopathies (CNM) are a group of congenital disorders characterized by hypotonia and skeletal muscle biopsies typically showing small rounded fibers with central nuclei [1,2,3,4]. 4 unrelated individuals with BIN1 mutations have been molecularly and clinically characterized to date [12,15] and this report is the first description of intrafamilal variability in two patients from a consanguineous family. Clinical analysis of respiratory and cardiac involvement diagnosed for the more severely affected male patient expand the phenotypic spectrum in autosomal recessive centronuclear myopathy.
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