Myotonic Dystrophy and Non-dystrophic Myotonias

Question 1

Warm-up Phenomenon

Answer 1

-repeated exercise or contractions typically improve myotonia

Question 2

Paramyotonia

Answer 2

-repeated exercise/contraction worsens myotonia i.e. in eyelid myotonia, repeatedly close/open eyes tightly, eyes wont open on 2nd or 3rd attempt

Question 3

Tongue Myotonia

Answer 3

-handkerchief knot after percussion

Question 4

Grip myotonia

Answer 4

-asses at hands by percussion of the thenar muscle and/or finger extensors

Question 5

Lid Lag mytonia

Answer 5

• delay in closure of the eyelid when patient asked to follow a target upward and then quickly downward
• delay is such that the sclera remains visible even when patient is looking down

Question 6

Myotonic Dystrophy

Answer 6

• CTG trinucleotide expansion >50 repeats
• Anticipation: genetic disorder more severe and occurs earlier in next generation
• AD

Question 7

Congenital Myotonic Dystrophy 1

Answer 7

• maternally inherited
• can be diagnosed prenatally in 1st trimester
• ->mother presents with polyhydraminos and reduced fetal movements

Clinical features:

• hypotonia
• swallowing and/or feeding difficulties
• dysarthria/speech delay
• bowel/bladder dysfunction
• myotonic facies + carp-shaped mouth (mid-face hypoplasia)
• club foot + tight heel cords
• respiratory distress
• ADHD/autism
• developmental delay
• psychomotor slowing
• less cardiac conduction issues but still increased risk of sudden cardiac death
• cardiomyopathy

Respiratory complications

Question 8

Childhood/Juvenile-onset myotonic dystrophy 1

Answer 8

• normal birth and motor development
• behavioral/cognitive symptoms (ADHD, Autism)
• sleep disturbances (PLMD, sleep apnea); daytime fatigue common!!

Question 9

Approach to neonate with myotonia

Answer 9

Hypotonia

• respiratory insufficiency
• sucking difficulties
• failure to thrive

1. ) without facial dysmorphism
   - CTG screening on DUPK gene
   - ->foot deformities (talipes)
   - ->positive family history DM1
   - -> SCN4A screening
   - ——->positive family history
   - ——->check K levels
   - ——->mild skeletal deformities

a. ) Negative CTG
- > Check CK
- > EMG studies
- > Muscle biopsy

b. ) Positive CTG
- > extend CTG screening to family members
- > Genetic counselling, family planning

2. ) With facial dysmorphism
   - contractures in face, limb, and trunk AND perform EMG

a. ) EMG
- -> continuous spontaneous activity, diffuse myotonic activity

Diagnosis of Schwartz-Jempel syndrome

b. ) EMG
- ->Myotonic discharges–> CTG screening (rule out acid maltase deficiency, hypothyroidism)

SCN4A and CLCN1 screening

Question 10

Adult-Onset Myotonic Dystrophy 1

Answer 10

• onset any age
• Weakness of distal hands/feet (wrist/finger EXTENSORS, dorsiflexion)
• progression to proximal muscle weakness
• FACE: bilateral ptosis, masseter/facial muscles, temporalis wasting (hachet facies–>atrophy of temporalis muscle), frontal balding, SCM wasting

Myotonia: “muscle stiffness”, warm-up phenomenon, percussion and grip myotonia, worse with cold temperature

• absent DTR
• muscle atrophy

a. )Cardiac: conduction issues
b. )Respiratory: restrictive lung disease, recurrent infections
c. )Sleep apnea, excessive sleepiness
d. )Bulbar: palatal, pharyngeal, tongue weakness, dysarthria, dysphagia
e. )GI: constipation, gallstones
f. )Cognitive: prominent apathy, obsessive, avoidant, suspicious
g. )Endocrine: reduced androgen–> testicular atrophy, gynecomastia, impotence, recurrent fetal loss, insulin resistance, vit D deficiency (hypoparathyroidism)
h. ) Cataracts–> polychromatic catarcts (“Christmas tree cataracts)
i. ) hypogammaglobulinemia
- myeloma, cancer, infection

Question 11

Myotonic Dystrophy Type 2

Answer 11

CNBP gene

• CCTG tetranucleotide repeat
• no anticipation
• AD
• Brisk reflex
• Extrapyramidal feature i.e.camptocormia
• Cognition normal
• Neck flexor weakness COMMON

1. )Proximal Myotonic Myopathy
   - mild/moderate proximal LE»UE (hip flexor and knee extensors) NO ATROPHY
   - calf hypertrophy
   - no atrophy
   - myotonia: triggered by cold
2. )Proximal Myotonic Dystrophy
   - Proximal LE>UE + ATROPHY
   - no myotonia

Question 12

Management of MD1

Answer 12

1. ) Surveilence for other things (remainder of body)
2. ) Myotonia: Mexiletine 200mg TID, Creatine, TCAs
3. ) Excessive daytime sleepiness: modafenil 100mg BID
4. ) Pregnancy: D/C Mexiletine (teratogenic), C-section

Question 13

Non-Dystrophic Myotonia

Answer 13

1. ) Chloride channel
   - Myotonia Congenita
2. ) Sodium channel
   - Hyperkalemic periodic paraylsis
   - Paramyotonia congenita
   - Potassium-aggravated myotonia

3.) Schwartz-Jampel syndrome

**eyelid myotonia is a feature of nondystrophic myotonia

Question 14

Non-Dystrophic Myotonia NCS/EMG and other tests

Answer 14

EMG: normal, myopathic or increased insertional activity

1. ) Short exercise test
   - useful for testing non-dystrophic myotonias
2. ) Long exercise test
   - useful for testing periodic paralyses

Question 15

Myotonia Congenita

Answer 15

CLCN1 mutation
Autosomal recessive (Becker MC)
Autosomal dominant (Thomsen MC)

Clinical:

1. ) hypertrophic, muscular build
2. ) stiffness, fatigue/pain
3. ) myotonia improves with exercise