Facioscapulohumeral muscular dystrophy is an autosomal dominant disease, though a family history may not be evident because expression of the disease can be mild. Phenocopies resulting from spinal muscular atrophy, mitochondrial myopathy and inclusion body myositis have been reported, but diagnosis by DNA analysis has greatly reduced diagnostic uncertainty in recent years. Weakness typically begins in the face (though the face may be unaffected in some individuals) or shoulder muscles, with sparing of the extraocular, pharyngeal and lingual muscles. Inability to whistle is characteristic. In later stages, dramatic scapular winging develops, and weakness of the scapular fixators allows ‘over-riding’ of the scapulae above the shoulders, like a pair of wings. Lower limb weakness may not be conspicuous, but foot drop and later proximal weakness can occur. Creatinine kinase levels, EMG and muscle biopsy may show only minimal abnormalities. Diagnostic confirmation depends on the demonstration of abnormally small 4q35-specific DNA fragments following digestion with restriction site enzymes. Recent evidence suggests an inverse correlation between the size of these fragments and disease severity. The genes responsible have not yet been identified. No treatment is available, but scapulothoracic arthrodesis can improve upper limb function in patients with severe limitation of arm elevation.
Oculopharyngeal muscular dystrophy presents with ptosis and weakness of the extraocular muscles, muscles of the pharynx and larynx (causing progressive dysphagia and dysphonia), and the facial, limb-girdle and even distal muscles. It is an autosomal dominant disorder, but gene penetrance varies considerably. Cases may be mild to severe and can present at almost any age, though typically in the sixth decade and beyond. Creatinine kinase may be only minimally increased and biopsy can show a range of changes which may include rimmed vacuoles and ragged red fibers typical of a mitochondrial myopathy. Ultrastructural studies may reveal pathognomonic accumulations of 8.5 nm filaments in a proportion of myonuclei. Recently, diagnosis by DNA analysis has become available. The disease is associated with a GCG triplet expansion at the poly-A binding protein 2 (PABP2) gene at 14q11. It is suggested that this expansion might cause mutated PABP2 monomers to aggregate in nuclei, resulting in filament accumulations.
Distal myopathies
Several neuromuscular diseases present with distal weakness and wasting of the limbs. This pattern commonly results from peripheral neuropathies, including Charcot–Marie–Tooth disease, and from anterior horn cell diseases such as spinal muscular atrophy. It can also be encountered in primary muscle diseases, notably myotonic dystrophy, congenital myopathies and inclusion body myositis. In addition, several rare forms of genetically determined distal myopathy have been described. These can be distinguished to some degree by mode of inheritance and whether the anterior or posterior compartment of the lower legs is principally affected. A common form is Miyoshi myopathy, which particularly affects the gastrocnemius and soleus muscles. Like LGMD2B, it is a dysferlinopathy. Several of these diseases are rimmed vacuolar myopathies, a feature shared with the hereditary inclusion body myopathies.
Congenital myopathies
Congenital myopathies are classified on the basis of specific histological features. Patients can present at any time from childhood to adult life, usually with distal weakness. A long, thin facies and high arched palate are common. This group of disorders includes centronuclear and myotubular myopathies, nemaline myopathy and central core disease.
Myotonic disorders
Myotonia is prolonged contraction of muscle, with subsequent slowed relaxation, following activation. It results from genetic or acquired changes in excitability of muscle surface membranes and is found in several primary muscle diseases. Neuromyotonia is a clinically similar phenomenon of neurogenic origin.
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