A Patient with Genetically Confirmed Myoclonus-Dystonia Responded to Anticholinergic Treatment and Improved Spontaneously

BACKGROUND: The various medical treatments applied to myoclonus-dystonia patients with a mutation of the epsilon-sarcoglycan gene (SGCE) have not been beneficial in most cases. Most patients experience progressive deterioration or static clinical courses, with only rare cases of spontaneous remission. CASE REPORT: A 19-year-old girl presented with a 14-year history of myoclonus and dystonia that severely affected her left arm, neck, and trunk. Genetic studies showed a mutation in SGCE [deletion in exon 6 (c.771_772delAT, Cys258X)]. Both myoclonus and dystonia responded to anticholinergic treatment for 7 years and improved spontaneously. CONCLUSIONS: The possibility of spontaneous improvement should be kept in mind when considering the therapeutic strategy in myoclonus-dystonia patients, especially when contemplating deep-brain stimulation.

Severe childhood autosomal recessive muscular dystrophy, mental subnormality and chorea.

Severe childhood autosomal recessive muscular dystrophy (SCARMD) is characterized by a severe Duchene muscular dystrophy like phenotype. Most such cases represent alpha or gamma sarcoglycanopathies. Mental subnormality is very uncommon and other central nervous system deficits have not been documented in patients with SCARMD. We report a brother and sister with the SCARMD phenotype, who additionally had static mental subnormality and choreiform movements. Work-up for sarcolgycan genes, dystrophin gene and known causes of mental retardation and chorea was normal.

Molecular and Pathological Diagnosis of Muscular Dystrophies / 한양의대학술지

The muscular dystrophies are a diverse group of inherited muscle disorders characterized by progressive muscle weakness and wasting with characteristic histologic abnormalities such as degeneration, necrosis, and regeneration of muscle fibers. With progress in molecular genetics methods, new discoveries of dystrophin and related molecules have dramatically changed the understanding and diagnosis of a large group of muscular dystrophy patients. Dystrophin and its related molecular associates are tightly associated and form an essential cytoskeletal system (dystrophin-glycoprotein complex) at the muscle fiber surface membrane, which is critical for maintaining the integrity of the sarcolemma and muscle fibers. Deficiency of one of these sarcolemmal proteins, including dystrophin, dystroglycans, sarcoglycans, and laminin-2, leads to the breakdown and instability of muscle fibers and to clinically observed progressive muscle weakness. Identification of the molecular cause of muscular dystrophies would allow a genetic oriented classification and diagnosis using DNA or protein analysis. However, definition of the molecular pathogenesis of muscular dystrophies has not been completely possible until now. Future advances in this field should allow the exact diagnosis and treatment of muscular dystrophies.

Dystrophin-glycoproteins associated in congenital muscular dystrophy: immunohistochemical analysis of 59 Brazilian cases

The congenital muscular dystrophies (CMD) are heterogeneous muscular diseases with early and dystrophic pattern on muscle biopsy. Many different subtypes have been genetically identified and most phenotypes not yet identified belong to the merosin-positive (MP) CMD subgroup. OBJECTIVE: To analyze the immunohistochemical expression of the main proteins of the dystrophin-glycoproteins associated complex in muscle biopsy of patients with different CMD phenotypes, for investigating a possible correlation with clinical and histopathological data. METHOD: Fifty-nine patients with CMD had clinical, histopathological and immunohistochemical data evaluated: 32 had MP-CMD, 23 CMD with merosin deficiency (MD-CMD), one Ullrich phenotype and three Walker-Warburg disease. RESULTS: Dystrophin and dysferlin were normal in all; among the patients with MD-CMD, merosin deficiency was partial in nine who showed the same clinical severity as those with total deficiency; the reduced expression of alpha-sarcoglycan (SG) and alpha-dystroglycan (DG) showed statistically significant correlation with severe MD-CMD phenotype. CONCLUSION: There is a greater relationship between merosin and the former proteins; among MP-CMD patients, no remarkable immunohistochemical/phenotypical correlations were found, although the reduced expression of beta-DG had showed statistically significant correlation with severe phenotype and marked fibrosis on muscular biopsy.

A distrofia muscular congênita (DMC) é doença muscular heterogênea, de início precoce e padrão histopatológico de distrofia. Diversos subtipos foram geneticamente identificados e os fenótipos ainda não identificados pertencem em geral ao subgrupo de DMC merosina-positiva (MP). OBJETIVO: Analisar a expressão imuno-histoquímica das principais proteínas do complexo distrofina-glicoproteínas associadas na biópsia muscular de pacientes com diferentes fenótipos de DMC, a fim de investigar uma eventual correlação com o quadro clínico e histopatológico. MÉTODO: Cinqüenta e nove pacientes com DMC foram avaliados clinicamente e sua biópsia muscular, histopatologica e imuno-histoquimicamente: 32 eram MP, 23 merosina-deficiente (MD), um mostrava fenótipo Ullrich e três síndrome de Walker-Warburg. RESULTADOS: Distrofina e disferlina foram normais em todos; nove pacientes MD apresentavam déficit parcial de merosina, porém com a mesma gravidade clínica daqueles com deficiência total. CONCLUSÃO: A hipoexpressão de a-sarcoglicana (SG) and a-distroglycan (DG) se correlacionou estatisticamente com o grave fenótipo MD, assim indicando maior correlação entre a merosina e as referidas proteínas; entre os pacientes MP, apesar da hipoexpressão de b-DG ter se correlacionado significativamente com fenótipo e histopatologia mais grave, não houve correlação clínica/imuno-histoquímica valorizável.

Beta-sarcoglycanopathy.

Sarcoglycanopathies are relatively rare progressive muscular dystrophies with autosomal recessive inheritance; which belong to the group of limb girdle muscular dystrophies. The phenotype resembles dystrophinopathies due to proximal muscle weakness and calf hypertrophy. Reports from the Indian subcontinent are scarce. The authors report a case of primary beta-sarcoglycanopathy and describe literature pertaining to this rare entity.

Sarcoglycanopathies: a clinicopathological study of 13 cases [corrected]

BACKGROUND: Limb girdle muscular dystrophy (LGMD) is a phenotypic expression of a heterogeneous group of diseases and sarcoglycanopathy is one of the causes of LGMD. There is only one study on sarcoglycanopathies in the Indian literature. No data is available from northern India. MATERIALS AND METHODS: All cases of muscular dystrophies, which were diagnosed in our laboratory in the last six years, were reviewed. Immunohistochemistry for various sarcoglycan proteins was done. Clinical features and pathological findings of the cases that were diagnosed as sarcoglycanopathies were reviewed. RESULTS: In the last 6 (1/2) years (1998-June 2004), we received 1435 muscle biopsies, of which 498 cases were of muscular dystrophies, and 13 cases were of sarcoglycanopathies (8 of gamma, 3 of alpha, 1 of both alpha and gamma, and 1 with absence of all four sarcoglycans). Sarcoglycanopathies comprised 2.6% of all muscular dystrophies, 11.8% of LGMD and 0.90% of all muscle diseases diagnosed in our laboratory. The mean age of onset was 7.2 years and the M:F ratio was 1.1:1. Most of them presented with difficulty in getting up, climbing stairs, calf hypertrophy and markedly raised CPK levels. Histological features were like dystrophinopathies. CONCLUSION: Sarcoglycanopathies are a relatively rare cause of LGMD and should be confirmed by immunohistochemistry as it will facilitate counseling and also prognostification. Although rare, in patients with muscle weakness, calves hypertrophy and raised CPK levels this possibility should be considered and needs to be differentiated from dystrophinopathies.

Significance of Immunohistochemical Study in Patients with Muscular Dystrophy

BACKGROUND: For the differential diagnosis between the various subtypes of muscular dystrophy, the analysis of the protein expression pattern from the biopsied skeletal muscle tissue is essential. Authors performed the immunohistochemical study (IHC) using sets of antibodies for the differentiation of subtypes of muscular dystrophy. METHODS: Antibodies against dystrophin C-terminal, dystrophin rod domain, dystrophin N-terminal, alpha-, beta-, gamma-sarcoglycans, laminin alpha2 chain, dysferlin, and beta-dystroglycan were used for the IHC study in 43 patients with muscular dystrophy. The reactivity against the specific antibodies was graded and the clinical findings were assessed. RESULTS: We found 15 cases of dystrophin deficiency and 7 cases of dysferlin deficiency. Those with dystrophin deficiency were clinically classified previously as follows, 11 cases with Duchenne's muscular dystrophy (DMD), two with congenital muscular dystrophy (CMD), one with Becker's muscular dystrophy (BMD), and a female patient with limb-girdle muscular dystrophy (LGMD). Those with dysferlin deficiency consisted of 4 cases with LGMD phenotype and 3 with distal myopathy. CONCLUSIONS: The results of our study confirm the dystrophin immunostain is essential for the identification of dystrophinopathies among the various subtypes of muscular dystrophy. Also, the identification of 7 cases with dysferlin deficiency suggests dysferlinopathy is the common cause of muscular dystrophy in Korea.

Adhalin deficiency: an unusual cause of muscular dystrophy.

Childhood muscular dystrophies have a wide clinical spectrum, motor disability and are variably inherited. Although the phenotype may appear similar they may represent distinct genetic entities. Advances in immunohistochemistry, gene deletion and linkage studies have enabled precise characterization. We report a family with an early onset weakness and calf pseudo hypertrophy in 2 male sibs with an usually mild course. Deletion screening was negative for 24 exons of the DMD gene in both. Muscle immunohistochemistry revealed normal dystrophin I and II staining but complete absence for adhalin, a dystrophin associated glycoprotein. Classifying them as adhalinopathy. Severe childhood autosomal recessive muscular dystrophies (SCARMD) result from mutation in the sarcoglycan complex (59). Adhalinopathy is now used to describe SCARMD. The adhalinopathy described in our patients is the first report from India.

Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.