Other Types of Muscular Dystrophy


FSHD is inherited in an autosomal dominant (AD) fashion with nearly complete penetrance and variable expressivity, with mild and severe cases seen in the same family. It is due to a deletion in the number of D4Z4 repeats in the subtelomeric region of chromosome 4q35. There is a correlation between disease severity and the size of deletion.


Treatment is aimed at encouraging activity and facilitating use of weakened limbs. Wrist splints and light foot braces are often helpful.


Oculopharyngeal muscular dystrophy (OPMD) is inherited as an autosomal dominant condition with onset in the fifth or sixth decades of life. OPMD is found in North American families of French-Canadian extraction but also observed in Spanish-American and in the Bukhara-Jewish population. The major clinical features are ptosis and dysphagia, which slowly progress over many years. Ptosis progresses to severe narrowing of the palpebral fissures. Over time, weakness involves the lid, extraocular, facial, neck, and proximal limb muscles in a symmetric fashion. The serum CK is normal or slightly elevated. The EMG discloses myopathic features.


OPMD is inherited in an autosomal dominant fashion, and the mutation is an 8- to 13-nucleotide expansion of a (guanine-cytosine-guanine [GCG]) 6-nucleotide repeat encoding for a polyadenylate (poly A) binding protein (PABP2), which, when expanded, is thought to cause toxicity to muscle cells by accumulating as intranuclear inclusions. Genetic testing is available to confirm the diagnosis. Dysphagia may be so severe that patients are in danger of aspiration pneumonia, dehydration, and malnutrition, and therefore a gastrostomy may be necessary.


Limb-girdle muscular dystrophy (LGMD) is inherited as either an autosomal recessive (AR) or dominant disorder and is in a category of muscular dystrophies that are distinct from the more common X-linked Duchenne and Becker dystrophies. The onset of weakness ranges from the first to the fourth decade, and the clinical course is one of slowly progressive muscle weakness and wasting with variable disability. The distribution of weakness usually spares the face and involves proximal and limb-girdle muscle groups predominantly. In most patients, the heart and respiratory muscles are spared, but exceptions occur depending upon the specific genetic subtype. The serum CK is invariably raised, the EMG reveals fibrillations and myopathic potentials, and the muscle biopsy discloses necrosis and regeneration.


Currently, 14 autosomal recessive and 7 autosomal dominant types have been identified. In most of the dominant forms, designated LGMD1, patients have been described in single, large, extended pedigrees and are considered rare. The recessive types, designated LGMD2, are more common, but prevalence is not easily ascertained. The autosomal recessive subtypes are listed alphabetically, from LGMD2A through LGMD2N. Among the 14 subtypes of LGMD2, the most common disorders are those associated with mutations in genes coding for calpain (LGMD2A), dysferlin (LGMD2B), alpha-sarcoglycan (LGMD2D), and Fukutin-related protein (LGMD2I). In addition to progressive proximal weakness, each of these disorders has distinctive features. Calpainopathy is characterized by elbow and wrist contractures and tight heel cords; dysferlinopathy, by involvement of calf muscles and muscle biopsy disclosing inflammatory infiltrates; sarcoglycanopathies, by strongly resembling dystrophinopathy (with calf hypertrophy) without cardiomyopathy; and Fukutin-related protein deficiency resembling Duchenne or Becker dystrophy, sometimes with cardiomyopathy and diaphragmatic weakness. To date, in approximately 50% of patients with LGMD2, a gene locus or defective protein product has not yet been determined.


In patients suspected of having a form of LGMD2, and after genetic testing has ruled out a dystrophinopathy, a muscle biopsy is generally obtained and evaluated with biochemical testing (immunostaining of candidate proteins). For many of the subtypes of LGMD2, genetic testing can be used to identify the specific disease-causing mutation. Patients with LGMD require a comprehensive approach to care best achieved with a multidisciplinary team. Although cardiac and respiratory complications are uncommon, heart assessment with an electrocardiogram (ECG), echocardiogram, and lung function evaluation are important to identify and treat proactively for possible underlying complications. Genetic counseling is of great importance to families, and prenatal diagnosis is available when the causative mutation has been established.


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Sep 2, 2016 | Posted by in NEUROLOGY | Comments Off on Other Types of Muscular Dystrophy

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