Miyoshi myopathy in Saudi Arabia

Abstracts"

461

Acknowledgement - Supported by Telethon Italy, grant 668.

MRI muscle imaging was described on an arbitrary basis using a scale from 0 to 4 ( 0 = n o r m a l ; l = m i n i m a l ; 2~<50%; 3 1> 50%; 4 = e n d stage). Our results show a severe and predominant involvement of the posterior compartment in the legs in both cases (grade 4). Medial, intermedius and lateral quadriceps show grade 3 muscle replacement, whereas the rectus femoris is unaffected in the youngest patient but is an end-stage muscle in the oldest patient. The biceps femori is end-stage in both patients. Six months and 2 years follow-up CT scans show a slowly progressive pattern in both patients, in contrast with the unchanged clinical findings on MMT. This indicates that the degenerative changes in MM are slow, but progressive, and better evaluated by muscle imaging. Tissue replacement on muscle imaging can be seen in single muscles which cannot be tested manually. CT and MRI muscle imaging are potential quantitative techniques, useful in the study of the natural history of MM.

DISTAL MYOPATHIES: P O S T E R DISCUSSION

Keywords: Distal myopathy; Miyoshi myopathy; Muscle imaging

DMP1 Autosomal dominant late adult onset distal myopathy I. Penisson-Besniera, C. Dumez a, D. Chateau b, F. Dubas ~, M. Fardeau b "Service de Neurologie A, CHU Angers, France, blnstitut de Myologie, 1NSERM U153, I-lbpital Pitir-Salp~trikre, Paris, France

DMP3 Distal myopathy of Miyoshi type: report of 21 French cases B. Eymard a, P. Laforet a, F,M.S. TomC, H. Collin a, J.P. Leroy b, J.J. Hauw ~, M. Fardeaub "INSERM U. 153, H3pital de la SalpOtribre, Paris, France, hService d'Anatomopathologie, Hg~pital de Brest, France, "Service de Neuropathologie, HOpital de la SalpOtribre, France

ments ranging in size between 10 and 28 kb in all but three families (96.7%). After BlnI digestion the EcoRI fragments were reduced by 3 kb in 85 families, confirming their 4q35 origin, but disappeared in two families. Since interchromosomal exchange between 4q and 10q chromosomes has been described to occur in 10% of normal individuals, BlnIsensitive repeats of 10qter origin translocated on a 4qter chromosome could be implicated in the molecular mechanism of the disease. In addition we found a variation in the number of pl3E-11 fragments after BlnI digestion in some individuals, but this does not interfere with the sensitivity and specificity of the double digestion technique.

Keywords: FSHD; 4q35 deletion; translocations

Four major subtypes of distal myopathies are to date distinguished according to the mode of inheritance, the age of onset and the first group of muscles involved [Somer H, Neuromusc Disord 1995;5:249252]. We identified a myopathy in a French kindred, characterized by: (1) an autosomal dominant inheritance; (2) a late onset (about age 60 years); (3) a distal leg weakness; (4) a normal or mildly elevated CK level; (5) striking histological features, similar to those described by Markesbery and Griggs [Markesbery et al., Neurology 1974;23:127-134], including hypertrophic fibers, marked vacuolar changes, and presence of focal collections of an homogenous material that stained basophilic with hematoxylin eosin, dark green with the Gomori trichrome method, dark blue with NADH-TR and immunoreacted with desmin; (6) presence of many autophagic vacuoles and rare tubulofilamentous inclusions. The propositus presented at age 63 with a marked steppage gait and a mild proximal weakness of the lower limbs predominating on the posterior compartment. His 60 year old sister had a predominant pelvifemoral muscle weakness and the CT scan disclosed early involvement of posterior distal leg muscles. The condition evolved slowly. Both of them later experienced mild proximal weakness of the upper limbs whereas distal groups were preserved as were facial muscles. There was no cardiomyopathy in the two siblings. Even though occasional rimmed vacuoles and tubulofilaments were observed, it is questionable to consider them as distinctive and prominent features. A molecular genetic analysis should be performed in order to clarify the nosology of this type of distal myopathy and of the autosomal dominant inclusion body myopathies [Askanas V. Ann Neurol 1997;41:421-422].

Keywords: Autosomal dominant distal myopathy; Late onset distal myopathy; Filamentous inclusions

DMP2 Progression of muscle involvement in Miyoshi myopathy by CT and MRI muscle imaging G. Meola a, V. Sansonea, G. Rotondo a, M. Sterlicchio a, A. Jabbour b a Department of Neurology and b Department of CT and MR1, University of Milan, San Donato Hospital, Milan, Italy The course and prognosis of Miyoshi myopathy (MM) is described as slow, and most patients retain the ability to walk until later in the disease. The aim of this study is to assess progression of muscle weakness by manual muscle testing (MMT), and by muscle imaging. We describe 2 patients with MM (male aged 43; female aged 28 from 2 unrelated families) after 6 months to 2 years follow-up. Muscle strength was assessed by MRC grading and degree of muscle replacement by CT and

We report 21 patients (12 males and 9 females), belonging to 20 families with the clinical and laboratory features of a distal myopathy of Miyoshi type. The main clinical features of these patients were: (1) onset in late adolescence or early adulthood (mean age 20.3 years), (2) early and predominant involvement of the posterior compartment muscles of legs, (3) marked elevation of serum CK (mean value 4473 U/l). Only in one family were there two affected sibs. All other cases were sporadic and a consanguinity of parents was found in 4 cases. The evolution was progressive, but all patients except one remain ambulatory. Muscle biopsy showed a dystrophic pattern. Some of these patients were initially considered as having polymyositis; immunosuppressive therapy was always ineffective. In conclusion, the Miyoshi distal myopathy is not uncommon, but this disorder is often misdiagnosed.

DMP4 Miyoshi myopathy in Saudi Arabia Edward J. Cupler, Saeed Bohlega, Richard Hessler, Bent Stigsby, Donald McLean The Department of Neurosciences, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, MBC 76, Riyadh 11211, Saudi Arabia

Objective. To document Miyoshi myopathy occurring in the Saudi population. Background. Miyoshi myopathy is an autosomal recessive or sporadic distal myopathy preferentially affecting the gastrocnemius muscles. Miyoshi myopathy has not been reported in the Saudi population. Methods. Two Saudi men, aged 25 and 40 years, developed progressive symptoms of calf wasting and muscle weakness over 10 months and 2 years. On examination, selective gastrocnemius atrophy was present in both. In one, deltoid, biceps and intrinsic hand musculature were graded 4+, ileopsoas 3, quadriceps, hamstrings and tibialis anterior 4, and gastrocnemius muscles 3 (MRC scale) while in the other, weakness was restricted to the gastrocnemius muscles. CK was 9585 and >20000 u/l, respectively (normal 0-195 U/l). Consanguinity or a family history was negative in both. Electromyography revealed small amplitude, short duration polyphasic motor units with fibrillation potentials and positive sharp waves in one. In some muscles large amplitude, long duration polyphasic motor unit potentials were interspersed. Nerve conduction studies were normal. Quadriceps muscle biopsies demonstrated a necrotizing myopathy with myophagocytosis, numerous degenerating and regenerating fibres, increased endo- and peri-mysial connective tissue, increased internal nuclei and moth-eaten fibres. Rare loci of lymphocytic infiltrates were also seen. No vacuoles were observed. Conclusion. We report two Saudi

462

Abstracts

patients with the classical findings of Miyoshi myopathy, including adult onset, preferential involvement of gastrocnemius muscles, markedly elevated CK and muscle biopsy demonstrating necrotizing myopathy. Identification of additional affected family members and other Saudi cases will aid in further characterising the genetics of this rare disorder.

Keywords: Distal myopathy; Miyoshi myopathy, Saudi Arabia DMP5 Distal myopathy and limb-girdle muscular dystrophy in the same family: one gene for different phenotypes? Corrado Angelini, Marina Fanin, Elisabetta Menegazzo Neurology Department, University of Padova, Italy We describe a family from southern Italy in which the 36-year-old propositus is affected by distal myopathy whereas his two sisters (40 and 33 years old) are affected by a 'limb-girdle' muscular dystrophy. They both have a waddling gait and weakness of pelvic and upper girdle muscles. Three additional siblings and both non-consanguineous parents are healthy. Muscle biopsy showed myopathic changes in the male patient and dystrophic features in the sisters. No rimmed vacuoles were observed. Dystrophin and alpha-sarcoglycan were normal. Linkage analysis, which is in progress in our family, will determine whether the same gene is involved in this family in which both a distal myopathy and limb-girdle phenotype is present. Distal myopathy has been already reported in association with limb-girdle muscular dystrophy. Recently, a large Scandinavian family has been described in which the same gene has been shown to be responsible for both disorders. Limb-girdle muscular dystrophy type 2B (LGMD2B) is an allelic variant of Nonaka's type distal myopathy. These autosomal recessive disorders have been mapped to chromosome 2p.

DMP6 Familial cardiomyopathy and distal myopathy with abnormal desmin accumulation and migration Thierry Kuntzer, Alexander Lobrinus, Robert C. Janzer, Jean-Marie Matthieu Service de Neurologie, lnstitut de Pathologic and Laboratoire de Neurochimie, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland With the aim to better characterise changes in skeletal and heart muscles and protein expressed by muscle cells, we report on a family where mother and daughter suffer from cardiomyopathy and distal myopathy. Early symptoms were related to atrioventricular block in both patients at the same age, but the mother later developed a severe heart failure which needed heart transplantation at the age of 56 years. Distal amyotrophy and weakness of distal upper and lower limbs appeared progressively in their twenties, with a further slow progression of the disease leading to bilateral foot drops in the forties of the mother. Lower limb CT scans revealed nonhomogeneous focal atrophy of predominantly distal muscles. Skeletal muscle biopsies and explanted heart were characterised by inclusion bodies that expressed strongly desmin and alpha-B-cristallin and weakly dystrophin and ubiquitin. Ultrastructurally, most inclusions corresponded to non-membrane bound granulo-filamentous material with disruption of myofibrils. An immunoblot analysis showed two desmin bands, the first at 53 kDa and the second at 49 kDa. In conclusion, this study of a distinct subtype of desminopathy underscores that skeletal and heart muscles share in common very similar muscle changes with abnormal desmin migration that may correspond to a defective desmin.

Keywords : Desmin; Distal myopathy; Cardiomyopathy DMP7 Miyoshi-type distal muscular dystrophy: clinical features of 24 Dutch patients W.H.J.P. Linssen~, M. De Visserh, N.C. Notermans c, J.H.J. Wokke c, P.A. Van Doorn d, C.J. H6weler ~, A.E.J. De Jager f

"Department of Neurology, St. Lucas Andreas Hospital, Amsterdam, bAcademic Medical Center, Universi~ of Amsterdam, LCenter for Neuromuscular Diseases, Universi~ Hospital, Utrecht, dAcademic Hospitals, Universities of Rotterdam, eMaastricht and tGroningen, The Netherlands The hallmarks of Miyoshi-type distal muscular dystrophy (MMD) are: (1) early adult onset of symmetrical muscle weakness and atrophy of the gastrocnemius, preventing the patient standing on tip-toe. (2) Elevation of serum creatine kinase (CK) activity (10-150 times the upper limit of normal). (3) Dystrophic changes in muscle biopsy. (4) Autosomal recessive inheritance. Objectives. To study the clinical features in all known cases of MMD in The Netherlands and to assess clinical follow-up in functional terms. Methods. Twenty-four MMD patients (19 men) are included in the study after careful selection on the basis of serum CK activity (at least 10 times the upper limit of normal) and re-evaluation of muscle biopsy (no rimmed vacuoles). Mean age is 38 years (range 2 0 61). Twelve of the 24 patients are non-familial cases. There were 6 sibs in 4 non-consanguineous families. Four patients were previously diagnosed as idiopathic hyper-CK-emia. Clinical follow-up was performed in 23 patients (WL). Results. The mean age at the onset of initial weakness in the calf muscles was 27 years (SD 10 years). However, in 2 patients (8%) onset was before 16 years and 7 patients (29%) had their first symptoms when older than 30 years. The disease started asymmetrically in one lower leg in 46% of the patients and persisted asymmetrically distributed in four (17%). Three of them had a late onset (43, 45 and 51 years). At follow-up the mean disease duration was 10 years (range 1-26 years). Within 4 years after the clinical onset of MMD 80% developed difficulty climbing stairs and 40% difficulty rising from a chair. One-third of the MMD patients had become wheelchair dependent within 10 years. Fifty percent of the patients had weakness of the biceps brachii, 20-30% of the deltoideus and triceps brachii. Progression of disease was significantly related to the disease' duration (P = 0.02). Conclusions. (1) Miyoshi myopathy is a progressive muscular dystrophy that may lead to wheelchair dependency. (2) Age of onset is not limited to early adulthood. (3) Weakness is often asymmetrical. (4) Idiopathic hyper-CK-emia may precede the onset of calf weakness.

DMP8 Distal myopathy of Miyoshi and Nonaka types: a clinical, pathological and quantitative EMG study of 7 cases J.M. Fernandez ~, J. Gamez b, C. Cervera b, J.A. Cortes c, F. Branas c, A. Teijeiro d, R. Fernandez d, S. Teijeira d, C. Navarro d ~Hospital Xeral-Cfes, Vigo, ~'Hospital Vail d'Hebron, Barcelona, 'Hospital Xeral-Calde, Lugo, aHospital do Meixoeiro, Vigo, Spain

Objective. Early adult onset distal dystrophy is rare in Europe. We present 7 patients belonging to 5 families. Family histories showed previous occurrence in two of the cases. Mode of inheritance was either autosomal recessive or sporadic. Patients and methods. The age of the patients ranged from 20 to 33 years. All patients underwent clinical and electromyographic examination and MRI studies. Muscle biopsy was performed in six cases. Results. All patients complained of progressive distal weakness, starting in the legs. Distal leg atrophy was evident in all cases and in four there was marked posterior compartment atrophy. ENG was normal. CNEMG showed severe myopathic changes in leg muscles, with profuse fibrillations and positive waves and brieL low amplitude, often polyphasic motor unit potentials. Turns/amplitude analysis was myopathic in both lower and upper limbs. Fibre density in the tibialis anterior was increased in all patients. Serum CK levels were increased from 7 to 20 fold. Muscle biopsy showed severe dystrophic changes in two cases, with fatty substitution and endomysial fibrosis. Moderate dystrophic changes were present in the other four biopsies, two of which showed prominent rimmed vacuoles, positive for ubiquitin and B-amyloid. Conclusions. The clinical features of early adult onset distal myopathy of the Miyoshi type (type I) include severe gastrocnemius involvement, whereas in the Nonaka type (type II) anterior compartment is more selectively affected. Muscle biopsy shows characteristic rimmed vacuoles in the Nonaka type, and this