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G.P.7.01 Facioscapulohumeral muscular dystrophy: A review of 76 patients
806
Abstracts / Neuromuscular Disorders 17 (2007) 764–900
contractions by limb immobilization, suggesting that the muscle contractions play a role in the skeletal muscle degeneration of mdx mouse muscles. After the sampling, soleus muscle was treated with collagenase and entire single muscle fibers were isolated from tendon-to-tendon using fine needles. The muscle satellite cells, neuromuscular junctions, and myonuclei were stained. Three types of muscle fibers with myonuclear distribution at either central, peripheral, or both central and peripheral regions were noted. Some fibers contained the central nuclei, arranged like a single chain, throughout the fiber length. The total number of myonuclei was the same in any fibers with different distribution of myonuclei. Further, peripheral nucleus was noted at the site where the central nucleus was missing. These results suggest that myonuclei might migrate from the center to the periphery of fiber, or vice versa, cross-sectionally. Most of the fiber properties, such as the number of satellite cells and neuromuscular junction, and fiber size were identical between fibers with different myonuclear distribution, suggesting that the fibers with central nuclei may not be necessarily immature.
1
Universita` di Padova, Padova, Italy; 2 Universita` di Verona, Verona, Italy; 3 Universita` di Torino, Torino, Italy; 4 Universita` di Pisa, Pisa, Italy
POSTERS 9 FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY AND OCULOPHARYNGEAL MUSCULAR DYSTROPHY
Sensorineural hearing loss characterizes the unusual infantile-onset form of Facioscapulohumeral muscular dystrophy (FSHD), whereas its presence in the typical adolescence-onset form appears controversial. We describe the findings of a multicenter investigation on possible auditory involvement in a series of 73 FSHD patients with a genetically confirmed diagnosis. Among them 49 adolescence-onset cases with no risk factors for deafness, were identified (mean age 37.8 years, 31 males and 18 females). These subjects were evaluated by otoscopic examination and pure tone audiometry. None were aware of hearing loss, while four had raised unilateral or bilateral pure tone audiometric thresholds at 4000 and 8000 Hz, when evaluated by standardized tables. However, their mean raw pure tone audiometric threshold values were not significantly different from those of 55 controls (mean age 37.1 years, 32 males and 23 females). By statistical analysis, moreover, age of onset as well as degree of muscular weakness and 4q35 EcoRI fragment size made no significant difference to auditory thresholds in our FSHD patients. The same evaluation on three patients with infantile-onset form of the disease (4q35 fragment size 10–13 kb) detected a clear-cut hearing impairment. On the whole, our study suggests that, while representing a clinical feature of early-onset FSHD, hearing loss does not characterize the typical form of the disease.
G.P.7.01
doi:10.1016/j.nmd.2007.06.153
doi:10.1016/j.nmd.2007.06.151
Facioscapulohumeral muscular dystrophy: A review of 76 patients Gomez-Moreno, M. 1,*; Carnal-Martin, P. 1; Caman˜o, P. 2; Alonso-Ortiz, A. 1; Gutierrez-Rivas, E. 1 1 Hospital 12 de Octubre, Madrid, Spain; 2 Hospital Donostia, San Sebastian, Spain Objectives: Facioscapulohumeral muscular dystrophy (FSHD) is the second most frequent muscular dystrophy in the adult population. It is a muscular disorder with a genetic origin. We want to report the great phenotypic heterogeneity of a same genotype. Patients and methods: We have made a descriptive and retrospective study of the clinical and genetic characteristics in 76 patients with FSHD studied at ‘‘12 de Octubre’’ Hospital through a systematic review of the clinical records. Results: The mean age at onset was 17.3 years. 60.81% of patients were women. Eighty percent had a positive family history. The most frequent symptoms for consultation were asymmetrical and proximal weakness in scapular girdle muscles and facial weakness. 24.32% of cases with a positive genetic result were asymptomatic. We found a family (5 patients) with clinically defined FSHD and genetic study different from the deletion in 4q35. In examination, the majority showed weakness in facial and scapular girdle muscles, but we also found patients with weakness in hip girdle and tibial anterior muscles, as well as skeletal manifestations and high-frequency hearing loss. Serum creatine kinase was mildly to moderately increased (1,500 IU/L). Electromyography found a myopathic pattern in 80% of patients. Muscle biopsy showed nonspecific myopathic changes, often with inflammatory infiltrates and lobulated fibres. Because of clinical variability, we had patients with a wrong first diagnosis (14%). Conclusion: The discovery of the genetic causes of hereditary myopathies has proved the limitations of classifications based only on clinical criteria. Faced with a patient with the diagnosis of FSHD, a comprehensive examination as well as a family genetic study are crucial. A genetic counselling is decisive. doi:10.1016/j.nmd.2007.06.152
G.P.7.03 Facioscapulohumeral dystrophy presenting as axial myopathy Eger, K. *; Traufeller, K.; Hobohm, J.; Deschauer, M.; Zierz, S. University Halle-Wittenberg, Neurology, Halle (Saale), Germany Introduction: Axial myopathy is a rare neuromuscular disorder characterized by selective involvement of the spinal muscles with a bent spine and/or drooping head and/or camptocormia as leading clinical features. The cause is still unclear and probably heterogenous. Facioscapulohumeral dystrophy (FSHD) is characterized by a pattern of muscle weakness involving the face, scapula, upper arm, lower leg, and hip girdle. Methods: We demonstrate three patients with predominant axial weakness. Diagnosis of FSHD was established in all three cases by genetic analysis at 4q35. Results: Age at onset was 68 years of one female, 50 years of another female and 75 years of a male patient. Family history was negative in two patients, positive in one patient. In all three cases the clinical picture was summarized as axial myopathy. There was no facial involvement. Slight additional weakness and atrophy of shoulder girdle muscles was seen in two patients. One patient showed additional weakness of the hip girdle and lower leg. Beevor’s sign was positive in two patients. CK level was rised 0.5-fold to 2-fold. Electromyogram showed myopathic pattern in paravertebral muscles and normal pattern in M. vastus in two patients. In one patient muscle biopsy revealed unspecific changes in M. biceps brachii and neurogenic changes in paravertebral muscle. Genetic analysis (EcoRI/ BlnI) revealed fragment length of 33, 24 and 24 kb. Discussion: In the case of the clinical picture of an axial myopathy FSHD should be considered. The cases also highlight that facial and shoulder girdle weakness can be missing in FSHD. Also the cases emphasize the heterogeneity of axial myopathy phenotype. doi:10.1016/j.nmd.2007.06.154
G.P.7.02
G.P.7.04
Multicenter study on occurrence of auditory impairment in facioscapulohumeral muscular dystrophy Pastorello, E. 1,*; Tonin, P. 2; Mongini, T. 3; Palmucci, L. 3; Siciliano, G. 4; Rimini, A. 1; Angelini, C. 1; Tomelleri, G. 2; Trevisan, C. 1
Beevor’s sign in facioscapulohumeral dystrophy Eger, K. *; Jordan, B.; Habermann, S.; Zierz, S. M.-Luther-University of Halle-Wittenberg, Department of Neurology, Halle/S., Germany
Abstracts / Neuromuscular Disorders 17 (2007) 764–900
contractions by limb immobilization, suggesting that the muscle contractions play a role in the skeletal muscle degeneration of mdx mouse muscles. After the sampling, soleus muscle was treated with collagenase and entire single muscle fibers were isolated from tendon-to-tendon using fine needles. The muscle satellite cells, neuromuscular junctions, and myonuclei were stained. Three types of muscle fibers with myonuclear distribution at either central, peripheral, or both central and peripheral regions were noted. Some fibers contained the central nuclei, arranged like a single chain, throughout the fiber length. The total number of myonuclei was the same in any fibers with different distribution of myonuclei. Further, peripheral nucleus was noted at the site where the central nucleus was missing. These results suggest that myonuclei might migrate from the center to the periphery of fiber, or vice versa, cross-sectionally. Most of the fiber properties, such as the number of satellite cells and neuromuscular junction, and fiber size were identical between fibers with different myonuclear distribution, suggesting that the fibers with central nuclei may not be necessarily immature.
1
Universita` di Padova, Padova, Italy; 2 Universita` di Verona, Verona, Italy; 3 Universita` di Torino, Torino, Italy; 4 Universita` di Pisa, Pisa, Italy
POSTERS 9 FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY AND OCULOPHARYNGEAL MUSCULAR DYSTROPHY
Sensorineural hearing loss characterizes the unusual infantile-onset form of Facioscapulohumeral muscular dystrophy (FSHD), whereas its presence in the typical adolescence-onset form appears controversial. We describe the findings of a multicenter investigation on possible auditory involvement in a series of 73 FSHD patients with a genetically confirmed diagnosis. Among them 49 adolescence-onset cases with no risk factors for deafness, were identified (mean age 37.8 years, 31 males and 18 females). These subjects were evaluated by otoscopic examination and pure tone audiometry. None were aware of hearing loss, while four had raised unilateral or bilateral pure tone audiometric thresholds at 4000 and 8000 Hz, when evaluated by standardized tables. However, their mean raw pure tone audiometric threshold values were not significantly different from those of 55 controls (mean age 37.1 years, 32 males and 23 females). By statistical analysis, moreover, age of onset as well as degree of muscular weakness and 4q35 EcoRI fragment size made no significant difference to auditory thresholds in our FSHD patients. The same evaluation on three patients with infantile-onset form of the disease (4q35 fragment size 10–13 kb) detected a clear-cut hearing impairment. On the whole, our study suggests that, while representing a clinical feature of early-onset FSHD, hearing loss does not characterize the typical form of the disease.
G.P.7.01
doi:10.1016/j.nmd.2007.06.153
doi:10.1016/j.nmd.2007.06.151
Facioscapulohumeral muscular dystrophy: A review of 76 patients Gomez-Moreno, M. 1,*; Carnal-Martin, P. 1; Caman˜o, P. 2; Alonso-Ortiz, A. 1; Gutierrez-Rivas, E. 1 1 Hospital 12 de Octubre, Madrid, Spain; 2 Hospital Donostia, San Sebastian, Spain Objectives: Facioscapulohumeral muscular dystrophy (FSHD) is the second most frequent muscular dystrophy in the adult population. It is a muscular disorder with a genetic origin. We want to report the great phenotypic heterogeneity of a same genotype. Patients and methods: We have made a descriptive and retrospective study of the clinical and genetic characteristics in 76 patients with FSHD studied at ‘‘12 de Octubre’’ Hospital through a systematic review of the clinical records. Results: The mean age at onset was 17.3 years. 60.81% of patients were women. Eighty percent had a positive family history. The most frequent symptoms for consultation were asymmetrical and proximal weakness in scapular girdle muscles and facial weakness. 24.32% of cases with a positive genetic result were asymptomatic. We found a family (5 patients) with clinically defined FSHD and genetic study different from the deletion in 4q35. In examination, the majority showed weakness in facial and scapular girdle muscles, but we also found patients with weakness in hip girdle and tibial anterior muscles, as well as skeletal manifestations and high-frequency hearing loss. Serum creatine kinase was mildly to moderately increased (1,500 IU/L). Electromyography found a myopathic pattern in 80% of patients. Muscle biopsy showed nonspecific myopathic changes, often with inflammatory infiltrates and lobulated fibres. Because of clinical variability, we had patients with a wrong first diagnosis (14%). Conclusion: The discovery of the genetic causes of hereditary myopathies has proved the limitations of classifications based only on clinical criteria. Faced with a patient with the diagnosis of FSHD, a comprehensive examination as well as a family genetic study are crucial. A genetic counselling is decisive. doi:10.1016/j.nmd.2007.06.152
G.P.7.03 Facioscapulohumeral dystrophy presenting as axial myopathy Eger, K. *; Traufeller, K.; Hobohm, J.; Deschauer, M.; Zierz, S. University Halle-Wittenberg, Neurology, Halle (Saale), Germany Introduction: Axial myopathy is a rare neuromuscular disorder characterized by selective involvement of the spinal muscles with a bent spine and/or drooping head and/or camptocormia as leading clinical features. The cause is still unclear and probably heterogenous. Facioscapulohumeral dystrophy (FSHD) is characterized by a pattern of muscle weakness involving the face, scapula, upper arm, lower leg, and hip girdle. Methods: We demonstrate three patients with predominant axial weakness. Diagnosis of FSHD was established in all three cases by genetic analysis at 4q35. Results: Age at onset was 68 years of one female, 50 years of another female and 75 years of a male patient. Family history was negative in two patients, positive in one patient. In all three cases the clinical picture was summarized as axial myopathy. There was no facial involvement. Slight additional weakness and atrophy of shoulder girdle muscles was seen in two patients. One patient showed additional weakness of the hip girdle and lower leg. Beevor’s sign was positive in two patients. CK level was rised 0.5-fold to 2-fold. Electromyogram showed myopathic pattern in paravertebral muscles and normal pattern in M. vastus in two patients. In one patient muscle biopsy revealed unspecific changes in M. biceps brachii and neurogenic changes in paravertebral muscle. Genetic analysis (EcoRI/ BlnI) revealed fragment length of 33, 24 and 24 kb. Discussion: In the case of the clinical picture of an axial myopathy FSHD should be considered. The cases also highlight that facial and shoulder girdle weakness can be missing in FSHD. Also the cases emphasize the heterogeneity of axial myopathy phenotype. doi:10.1016/j.nmd.2007.06.154
G.P.7.02
G.P.7.04
Multicenter study on occurrence of auditory impairment in facioscapulohumeral muscular dystrophy Pastorello, E. 1,*; Tonin, P. 2; Mongini, T. 3; Palmucci, L. 3; Siciliano, G. 4; Rimini, A. 1; Angelini, C. 1; Tomelleri, G. 2; Trevisan, C. 1
Beevor’s sign in facioscapulohumeral dystrophy Eger, K. *; Jordan, B.; Habermann, S.; Zierz, S. M.-Luther-University of Halle-Wittenberg, Department of Neurology, Halle/S., Germany