1. University of Colorado
Limb Girdle Muscular Dystrophies Diagnosis and Treatment in the Genetic Era
Matthew P. Wicklund, MD
University of Colorado

2. Disclosure Information Matthew P. Wicklund, MD
Disclosure of Relevant Financial Relationships
I have the following financial relationships to disclose:
Scientific Advisory Board for: In-Depth Genomics
Speaker’s Bureau for: None
Grant/Research support from: Sanofi-Genzyme, Sarepta
Research Collaboration sans compensation: Jain Foundation, Athena Diagnostics
Stockholder in: None
Honoraria from: Sanofi-Genzyme, MDA
Employee of: None
Disclosure of Off-Label and/or investigative Uses
I may discuss the following off label use and/or investigational use in my presentation: Corticosteroids and genetic-based therapies in muscular dystrophies.

3. Learning Objectives
Illustrate the genetic variability of limb girdle muscular dystrophies (LGMDs).
Delineate optimal, cost effective strategies for diagnosis of LGMDs.
Develop an understanding of genetic therapies for LGMDs, understanding translatability of these techniques across disease.
Introduce future paradigms related to management of muscle disorders.

4. Introduction

5. History 1954 - Walton and Nattrass
Proposed LGMD as a distinct clinical entity
Initially distinguished cases from the 3 most common muscular dystrophies…

9. “Limb Girdle Muscle Weakness”
“Post-natal onset of progressive weakness and muscle atrophy affecting proximal muscles of the upper and lower extremities”

10. Variability
Genetic
Pathogenic
Regional/Ethnic
Phenotypic

11. Limb Girdle Weakness 15 autosomal recessive LGMDs
3 autosomal dominant LGMDs

12. Limb Girdle Weakness 9 distal myopathies 15 autosomal recessive LGMDs
3 autosomal dominant LGMDs
9 distal myopathies

13. Limb Girdle Weakness 6 Emery Dreifuss muscular dystrophies
15 autosomal recessive LGMDs
3 autosomal dominant LGMDs
9 distal myopathies
6 Emery Dreifuss muscular dystrophies

14. Limb Girdle Weakness 26+ autosomal recessive LGMDs
10+ autosomal dominant LGMDs
9+ distal myopathies (1A, 1E, 2B, 2L)
7+ EDMD (1B)
13+ myofibrillar myopathies (1A, 1E)
7+ metabolic myopathies
3+ myotonic disorders
2 dystrophinopathies (Becker & carriers)
2 FSHD
1 lysosomal storage disease
80+ genes in total

15. LGMD and Other Muscular Dystrophies
FSHD1
FSHD2
DM DM1