Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Novel Form of an Autosomal Dominant Vacuolar Hereditary Myopathy.
Castro5, Christine, Aksentijevich6, Ivona, Remmers6, Elaine, Rushing1, Elisabeth, Bianconi3, Simona, Huizing4, Marjan, Wilson6, Mildred
Armed Forces Institute of Pathology
National Institues of Health/National Human Genome Research Institute/Medical Genetics Branch
National Institutes of Health
National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch
National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD
National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Inclusion body myositis (IBM) is a slowly progressive skeletal muscle disease of unknown etiology with both sporadic and familial forms. The disease is characterized by proximal and often asymmetric distal muscle weakness, often with quadriceps atrophy. Muscle biopsy often shows degenerating and regenerating muscle fibers, perimyofiber distribution of inflammatory cells, and occasional red-rimmed vacuoles on Gomori trichrome staining. The most distinguishing feature is lack of response to immunomodulatory therapy. In familial IBM, disease onset often occurs in the late-teens to mid-20s; a Finnish form occurs in the 40s. Conversely, the sporadic form often occurs in those over age 50.
We identify what we believe is a new familial form of IBM in one family with 3 generations demonstrating onset after age 50. In the third generation, 5 of 10 siblings are clinically affected, suggesting autosomal dominant inheritance. Results of muscle biopsy, EMG and MRI are consistent with IBM.
Methods and Materials:
Subjects include 10 siblings (5 affected) ages 47 to 64, their unaffected father (age 86) and affected mother (age 70). They are of German and Dutch descent. Blood samples were obtained from all siblings and from the father. (A histology block of an endometrial biopsy from many years ago was obtained from the deceased mother.) MRI of bilateral thighs (T1-weighted and STIR images) was performed on 7 siblings. Muscle biopsy of the right quadriceps was done on 7 siblings and sent to Armed Forces Institute of Pathology for processing. DNA was extracted from blood of the 10 siblings, from their father, and the endometrial biopsy of the mother (later not used due to poor quality). Linkage analysis was performed and genotype data was analyzed via a program designed to identify the maternal haplotype transmitted to each child. Selected genes from the candidate interval were sequenced.
MRI images from the 5 affected subjects showed edema, fatty replacement, muscle atrophy and/or fascial enhancement. The 2 unaffected subjects were normal. Histology revealed abnormalities including vacuoles on Gomori trichrome stain, degenerating and regenerating muscle fibers, fiber size variation, and presence of angular atrophic fibers in all 7 siblings. Through genetic analysis, a 3 megabase region of interest was found on chromosome 12. To date, no genes have been located.
We present a family with a seemingly autosomal dominant late onset vacuolar myopathy. Linkage analysis and gene sequencing has led us to chromosome 12 where a 3 megabase region peaks our interest. However, we have not yet isolated a gene. Characterization of this family's disease is of great interest because hereditary or familial forms of any IIM provide genetic information to further our understanding of this disease process as well as identify individuals who would be most affected by such diseases.
To cite this abstract, please use the following information:
Castro, Christine, Aksentijevich, Ivona, Remmers, Elaine, Rushing, Elisabeth, Bianconi, Simona, Huizing, Marjan, et al; A Novel Form of an Autosomal Dominant Vacuolar Hereditary Myopathy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :914