Disorders of NMJ and Skeletal Muscle

Question 1

Mysthenia gravis

Answer 1

Clinical phenotype: fatigable proximal muscle weakness, prominent ocular and bulbar involvement
Molecular defect: antibodies against muscle nicotinic acetylcholine receptor, muscle specific kinase or Lrp4

Question 2

Lambert-Eaton myasthenic syndrome

Answer 2

Clinical phenotype: Fatigable proximal muscle weakness, prominent autonomic symptoms
Molcular defect: antibodies against P/Q type voltage gated Ca channel

Question 3

Duschenne and Becker muscular dystrophy

Answer 3

Clinical phenotype: Childhood onset of proximal muscle weakness, including neck flexors
Molcular defect: dystrophin gene mutation

Question 4

Limb-girdle muscular dystrophy

Answer 4

Clinical phenotype: proximal muscle weakness
Molecular defect: genetic mutations in sarcoglycan or one of several other structural proteins, including calpain, caveolin, dysferlin

Question 5

Myotonic dystrophy

Answer 5

Clinical phenotype: distal muscle weakness and stiffness, myotonia, systemic features
Molecular defect: intronic tri/tetra-nucleotide repeat expansion in DMPK and ZNF9 genes

Question 6

Facioscapulohumeral muscular dystrophy

Answer 6

Clinical phenotype: Asymmetric weakness predominately affecting the face, shoulder girdle and upper arms
Molecular defect: activation of DUX4 gene as a result of contraction of the D4Z4 repeat on 4q35

Question 7

Emery-Dreifuss muscular dystrophy

Answer 7

Clinical phenotype: early onset of joint contractures, humeroperoneal pattern of muscle weakness
Molecular defect: emerin and lamin A/C gene mutation

Question 8

Hypokalemic periodic paralysis

Answer 8

Clinical phenotype: episodes of generalized weakness lasting hours to days
Molecular defect: skeletal muscle channelopathy (most commonly L-type voltage gated Ca channel)

Question 9

Hyperkalemic periodic paralysis

Answer 9

Clinical phenotype: episodes of generalized weakness lasting minutes to hours
Molecular defect: skeletal muscle channelopathy (voltage gated Na channel)