Neuromuscular Genetics

Question 1

Autosomal Dominant
Mutation in the gene that codes for zinc finger 9 (ZNF9) on chromosome 3q21 in the form of expanded CCTG repeats
Myotonia + PROXIMAL weakness
Path: Muscle fiber size variability, Multiple internalized nuclei, Atrophic fibers with nuclear clumps

Answer 1

Proximal Myotonic Myopathy (PROMM) | Myotonic Dystrophy Type II

Question 2

Mutation in the Myotonic Dystrophy Protein Kinase (DMPK) gene located on chromosome 19q13.3

Answer 2

Myotonic Dystrophy Type I

Question 3

Mutation in the slow beta cardiac myosin heavy chain 1 (MyHC1) gene or MYH7 located on chromosome 14q11

Answer 3

Laing Myopathy

Question 4

Deficiency of the peroxisomal enzyme phytanoyl-coenzyme A (CoA) hydroxylase which leads to accumulation of phytanic acid

Answer 4

Refsum Disease

Question 5

SMN1 gene mutation (Survival of the Motor Neuron gene)

Answer 5

Infantile Spinal Muscular Atrophy | Werdnig-Hoffman Disease

Question 6

Anti-GM1 (ganglioside-monosialic acid)

Answer 6

Multifocal Motor Neuropathy

Question 7

Peripheral Myelin Protein-22 (PMP22)

Answer 7

Charcot-Marie-Tooth Disease Type 1-A

Question 8

Myelin Protein Zero (MPZ)

Answer 8

Charcot-Marie-Tooth Disease Type 1-B

Question 9

Mitofusin 2 (MFN2)

Answer 9

Charcot-Marie-Tooth Disease Type - 2

Question 10

Autosomal Dominant
Type 1: Caused mutation in Calcium Channel Gene CACNA1S on chromosome 1
Type 2: Mutation in in sodium channel gene SCN4A
Weakness without myotonia
Triggered by exercise & carb-rich meals
Labs: Elevated CK

Answer 10

Hypokalemic Periodic Paralysis

Question 11

Autosomal Dominant
Mutation in in sodium channel gene SCN4A
Triggered by resting after exercise

Answer 11

Hyperkalemic Periodic Paralysis

Question 12

Autosomal Recessive
Mutation of Fukutin Gene on Chromosome 9
Hypotonic and Floppy + Joint contractures at hip/knee/ankles + Developmental Delay, Seizures
Elevated CK
Path: Dystrophic changes, reduced alpha-dystroglycan
Brain MRI: Abnormal gyration in the frontal lobes

Answer 12

Fukuyama Congenital Muscular Dystrophy

Question 13

Mutation in Laminin-alpha-2 gene - Encodes for protein Meroisn
Hypotonia and generalized weakness (extraocular, facial muscles spared) + Contractures in hips & feet
No developmental delay

Answer 13

Merosinopathy Laminin-alpha-2 Deficiency

Question 14

Autosomal Dominant
Deletions of D4Z4 on chromosome 4
Facial and shoulder weakness (Winged Scapula, Difficulty raising arms above head)
Atrophic proximal UE
Beevor Sign = Umbilicus moves upward with neck flexion
Weak Dorsiflexion

Answer 14

Fascioscapulohumeral Muscular dystrophy (FSHD)

Question 15

Autosomal Dominant
GCG repeat expansion in the poly-A-binding protein 2 on chromosome 14
CK normal
Path: Variation in fiber size, rimmed vacuoles, intranuclear tubular filaments

Answer 15

Oculopharyngeal Muscular Dystrophy

Question 16

Spinal Muscular Atrophy

Answer 16

Survival Motor Neuron 1 Gene

Question 17

Adrenomyeloneuropathy

Question 18

Adrenomyeloneuropathy

Answer 18

X-linked
ABCD1 gene on chromosome Xq28

Question 19

Emery Dreifuss Syndrome

Answer 19

Autosomal Dominant: LMNA gene
X-linked: Emerin gene

Question 20

Mutation in the RET proto-oncogene

Absence of Myenteric Plexus resulting in maldevelopment

Answer 20

Hirschsprung’s Disease