Table 5.

Characteristics of Common Autosomal Dominant Limb Girdle Muscular Dystrophies (AD-LGMD)

	LGMD 1A	LGMD 1B	LGMD 1C
U.S. Prevalence	4,200	2,850	675
Inheritance	AD	AD	AD
Gene Location	5q31	1q11-q21	3p25
Protein	Myotilin	Lamin A/C	Caveolin-3
Onset	Variable Third to seventh decade Anticipation: age of onset decreases in succeeding generations	< 20 years	5 years to adulthood
Severity & Course	Slow progression	Slow progression Upper limbs involved by third or fourth decade	Moderate severity and progression Adults with Gower’s maneuver
Weakness	Legs and arms Symmetric Proximal at onset Early foot drop Distal with disease progression Wrist and finger extensors + deltoid Dysarthria (30%) Facial (17%) Neck extensors in some patients	Lower limb Symmetric Proximal Variant: Quadriceps weakness with Arg377His mutation	Proximal
Ambulation Status	Late loss of ambulation (> 10 years after onset)		Mild: Adults continue to ambulate with Gower’s maneuver
Cardiac	Cardiomyopathy 50% Onset 6th or 7th decade	Cardiomyopathy 62% AV conduction block	No Cardiomyopathy
Respiratory	Mild restrictive lung disease	Mild restrictive lung disease	Mild restrictive lung disease
Muscle size	–	–	Hypertrophy of calf
Musculo-skeletal	Contractures: ankles (30%)	No contractures	Cramps after exercise
CNS	No intellectual defect reported	No intellectual defect reported	No intellectual defect reported
Muscle pathology	Myopathic Variable fiber size Fiber degeneration and regeneration Rimmed vacuoles Normal levels of Myotilin or increased immunostaining Reduced laminin-gamma1 Type I predominance with increasing weakness Normal Dystrophin & Sarcoglycan	Laminin A subcellular localization: Normal: Nucleus; Co-localizes with Emerin Mutated: May aggregate in nucleus & be present in cytoplasm	Myopathic Reduced caveolin-3 staining: No 21-kD band on Western blot
Blood chemistry	CK: 1 to 15 times normal; commonly twice normal	CK: Normal to mildly elevated	CK: 4 to 25 times normal