Limb Girdle Muscular Dystrophies

Diagnosis and Treatment in the Genetic Era

Matthew P. Wicklund, MD
University of Colorado
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.
Learning Objectives
1. Illustrate the genetic variability of limb girdle muscular dystrophies (LGMDs).

2. Delineate optimal, cost effective strategies for diagnosis of LGMDs.

3. Develop an understanding of genetic therapies for LGMDs, understanding

translatability of these techniques across disease.

4. Introduce future paradigms related to management of muscle disorders.

 History
• 1954 - Walton and Nattrass
▫ Proposed LGMD as a distinct clinical entity
▫ Initially distinguished cases from the 3 most
common muscular dystrophies…
“Limb Girdle Muscle Weakness”

• “Post-natal onset of progressive weakness and

muscle atrophy affecting proximal muscles of the
upper and lower extremities”
Variability
• Genetic
• Pathogenic
• Regional/Ethnic
• Phenotypic
Limb Girdle Weakness
• 15 autosomal recessive LGMDs
• 3 autosomal dominant LGMDs
Limb Girdle Weakness
• 15 autosomal recessive LGMDs
• 3 autosomal dominant LGMDs
• 9 distal myopathies
Limb Girdle Weakness
• 15 autosomal recessive LGMDs
• 3 autosomal dominant LGMDs
• 9 distal myopathies
• 6 Emery Dreifuss muscular dystrophies
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
LGMD and Other Muscular Dystrophies

FSHD1
FSHD2

DM2 DM1