Abstract Details

Title Limb-Girdle Muscular Dystrophy Type 2E: Clinical, Genetic and Histopathological Features of 27 European Patients

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 031

Objective

Background BACKGROUND: LGMD2E is a rare muscular dystrophy due to the mutations in beta-sarcoglycan gene.LGMD2E is usually severe, but that has only been reported in few case studies.

Design/Methods DESIGN/METHODS: All LGMD2E patients followed at three European neuromuscular centres were included. The past medical history was collected, and disease course was evaluated by specific questionnaires. Molecular analysis of SGCB gene and histopathological features of muscle biopsies were reviewed.A specific evaluation protocol was created, including clinical-instrumental quantitative evaluation of motor, respiratory and cardiac function.

Results RESULTS: 27 patients (15M-12F,9-66yrs) from 22 families were included. Two populations could be identified according to disease severity: a severe form (n=17) with onset<10yrs (median 3yrs) and early loss of ambulation (13/17pts,median 12yrs) and a milder form (n=10) with later onset (median 13.5yrs) and slower progression (3pts wheelchair-bound at 35-59yrs, two patients ambulant at 50 and 66yrs).Fifty-one mutated alleles were identified (14 mutations) in 26 patients; two mutations were recurrent, associated with the severe form (c.376_383dup, 13/34 alleles) or the milder form (c.-22_10dup32, 8/20).Sarcoglycan complex analysis was available for 18 cases: the entire complex was undetectable in 9/11 severe and 0/7 milder patients; other patients showed a variable reduction in sarcoglycans. A hypokinetic or dilated cardiomyopathy was observed in 12patients (44%,median 28.5yrs). Six patients had a restrictive respiratory insufficiency requiring ventilation (22%,median 39yrs). Two patients had died at the age of 14 and 60 from cardiomyopathy and pneumonia.

Conclusions CONCLUSIONS: This study reports the largest series of LGMD2E patients to date, demonstrates the phenotypic spectrum of LGMD2E, and identifies two mutations predictive of the disease course. The LGMD2E phenotype is associated with a high incidence of cardiomyopathy and less frequent respiratory insufficiency.

Authors/Disclosures
Claudio Semplicini PRESENTER	No disclosure on file
	No disclosure on file
Bruno Eymard, MD	No disclosure on file
	No disclosure on file
Nanna Witting, MD, PhD (Danish National Hospital,Dept. Neurology)	No disclosure on file
	No disclosure on file
Corrado Angelini, MD, FAAN (Università Di Padova)	Dr. Angelini has nothing to disclose.
	No disclosure on file
	No disclosure on file
John Vissing, MD (Rigshospitalet)	Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Prof. Vissing has received personal compensation in the range of $0-$499 for serving as a Consultant for Denali Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Italfarmaco. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Prof. Vissing has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson & Johnson (Janssen). Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Edgewise Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Prof. Vissing has received research support from Rigshospitalet. The institution of Prof. Vissing has received research support from Avidity. The institution of Prof. Vissing has received research support from Sanofi. The institution of Prof. Vissing has received research support from Roche. The institution of Prof. Vissing has received research support from AnnJi.
Elena Pegoraro, MD, PhD (University of Padova)	No disclosure on file
Marco Capobianco, MD	No disclosure on file
Pascal Laforet (Hopital Pitie Salpetriere)	No disclosure on file

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