Abstract Details

Title Limb Girdle Muscular Dystrophy 1F: Clinical, Molecular and Ultrastructural Study

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 032

Objective

Background BACKGROUND: The LGMDs are a heterogeneous group of hereditary disorders with weakness in proximal limb and/or distal muscles. To date 8 autosomal dominant forms of LGMD are known. LGMD1F clinical phenotype is characterized by a great variability, ranging from early onset, with a severe and rapidly progression to milder slow late-onset forms. The clinical and morphological features of patients with LGMD1F had not yet sufficiently characterized to suggest a specific etiology.

Design/Methods DESIGN/METHODS: We collected the clinical history in 19/60 patients and expanded the family pedigree. Muscle biopsy histopathology, immunohistochemistry (desmin, myotilin, p62) and electron microscopy was investigated in one pair of affected patients (mother 1 biopsy, index patient 2 consecutive biopsies at 9 and 22 years). DNA from 4 patients was studied by Agilent MotorChip CGH array platform to identify the causative gene.

Results RESULTS: Age of onset ranged from 2 to 35 years; in half cases there was hypotrophy both in proximal upper and in lower extremities in calf muscles. We noticed a discrepancy between the clinical severity and muscle biopsy involvement: the daughter (index case) has a more severe clinical course and increased muscle fiber atrophy whereas the mother has a compromised muscle histopathology (more muscle fiber variation, and autophagic changes). Accumulation of desmin and myotilin and p62-positive aggregates was observed. Electron microscopy revealed accumulation of myofibrillar bodies in muscle fibers. Muscle MRI in the index patient showed selective and severe atrophy in the vastus lateralis.

Conclusions CONCLUSIONS: Our morphological and ultrastructural data seem to suggest a myopathy phenotype similar to those described for Z-disk diseases. Although the specific genetic defect is still unknown, it is possible to hypothesize that LGMD1F might lead to disarrangement of desmin-associated cytoskeletal network.

Authors/Disclosures
Corrado Angelini, MD, FAAN (Università Di Padova) PRESENTER	Dr. Angelini has nothing to disclose.
	No disclosure on file
	No disclosure on file
Beatrice Pignolet	Beatrice Pignolet has nothing to disclose.
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��