Myotonic dystrophy

Learning objectives

Describe the causes and symptoms of myotonic dystrophy
Diagnose and treat myotonic dystrophy
Manage myotonic dystrophy patients presenting for surgery

Background

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by muscle dystrophy starting in early adulthood
Myotonic dystrophy type I (DM1, Steinert disease) and type II (DM2, proximal myotonic myopathy, milder form of type I)
Multisystem disorder affecting somatic and smooth muscle, as well as ophthalmological, cardiovascular, endocrine, and central nervous systems

Etiology

Genetic disorder caused by an expansion of DNA tandem repeats, resulting in an RNA gain of function mutation
DM1 is caused by an expansion of a CTG repeat in the 3’-untranslated region of the DM1 protein kinase gene
DM2 is caused by the expansion of a CCTG repeat in the intron of the CCHC-type zinc finger nucleic aced-binding protein gene
DM is the most common muscular dystrophy in the European population
DM1 is more common than DM2

Signs & symptoms

Can range from potentially lethal in infancy to mild in late adulthood
DM1 is classified into three types:
- Congenital myotonic dystrophy
  - Fetal-onset involvement of muscle and central nervous system
  - Reductions in fetal movement and polyhydramnios
  - Equinovarus and ventriculomegaly on fetal ultrasound
  - Neonatal mortality rate ~18%
  - Childhood/adulthood: Characteristic tented appearance of the upper lip that results from facial diplegia, marked dysarthria, expressive aphasia, hypotonia rather dan myotonia
  - Frequent respiratory involvement
- Mild myotonic dystrophy
  - Mild muscle weakness, myotonia, and cataracts
  - Onset between 20-70 years of age (typically after 40)
  - Usually normal lifespan
- Classic myotonic dystrophy
  - Onset during the second, third, or fourth decade of life
  - Myotonia is the primary initial symptom
  - Characterized by “warm-up phenomenon”: Symptoms appear more pronounced after rest and improve with muscle activity
  - Distal muscle weakness is the main symptom, leading to impairment of fine motor tasks with the hands and impaired gait
  - “Myopathic face”: due to weakness and wasting of facial, levator, palpebrae, and masticatory muscles
  - Cardiac conduction abnormalities are common
  - Reduced lifespan
DM2:
- Manifests in adulthood (median age 48 years) with a variable presentation
- Early-onset cataract, varying grip myotonia, proximal muscle weakness or stiffness, hearing loss, myofascial pain
- Weakness and/or myalgias are the most common initial symptoms
- Mostly axial and proximal muscle weakness affecting the neck flexors, long finger flexors, hip flexors, and hip extensors
- Abdominal, musculoskeletal, and exercise-related pain
- Sometimes misdiagnosed as fibromyalgia

Diagnosis

Genetic testing
Elevations in alkaline phosphatase, gamma-glutamyl transferase, serum aspartate aminotransferase, and serum alanine aminotransferase in 30-50% of patients
Electrodiagnostic testing:
- Motor nerve conduction studies: Decreased amplitude with normal latency and normal conduction velocity
- Sensory nerve conduction studies: Typically normal
- Electromyography:
  - Sustained runs of positive sharp waves
  - Trains of negative spikes
  - Fluctuating amplitude and frequencies
Muscle biopsy: Type I fiber atrophy, Type 2 fiber hypertrophy, irregular fiber size, rows of internal nuclei, fibrosis, myofibrils oriented perpendicular to muscle fiber

Differential diagnosis

Schwartz–Jampel Syndrome
Duchenne muscular dystrophy
Hyperkalemic Periodic Paralysis (HPP)
Paramyotonia Congenita (PC)
Myotonia Congenita
Myotubular myopathy
Acid maltase deficiency
Debrancher deficiency
Inflammatory myopathies
Hypothyroid myopathy
Chloroquine myopathy
Statin myopathy
Cyclosporine myopathy

Treatment

No curative treatment, therapy is supportive and consists of monitoring and treating the issues associated with DM

Cardiovascular	Annual ECG monitoring for cardiac conduction disturbances Baseline cardiac imaging every 1 to 5 years
Pulmonary	Obtaining baseline and serial pulmonary function testing to monitor for neuromuscular respiratory failure
Daytime somnolence and obstructive sleep apnea	Evaluate for sleep apnea and treat if necessary Consider neurostimulants (e.g., methylphenidate) for excessive sleepiness
Ocular involvement	Annual eye exam Surgical removal of cataracts
Obstetrics and gynecology	High-risk obstetrics evaluation for patients who are pregnant or considering pregnancy
Endocrine issues	Baseline and annual fasting blood glucose and hemoglobin A1C Screening for hypothyroidism Treat erectile dysfunction if necessary
Myotonia	Medications such as mexiletine, tricyclic antidepressants, benzodiazepines, or calcium antagonists reduce sustained myotonia Sodium channel blockers are contraindicated in patients with second and third-degree heart block
Muscle weakness	Physical and occupational therapy to strengthen muscles

Complications

Central nervous system	Intellectual disabilities Cerebrovascular accidents Anxiety and depression Hypersomnia and sleep apnea Ventriculomegaly
Ophtalmologic	Cataracts Hyperopia Astigmatism
Cardiac	Atrial arrhythmias Conduction system slowing Ventricular arrhythmias Cardiomyopathy Early-onset heart failure
Pulmonary	Pneumonia Increased risk of anesthesia-related pulmonary complications
Gastrointestinal	Dysphagia Gallstones and cholecystitis Tranaminitis and liver enzyme elevations Increased risk of post-anesthesia aspiration
Endocrine	Insulin insensitivity Testicular atrophy and male infertility Increased risk of abortion, miscarriage, pre-term birth, dysmenorrhea
Dermatologic	Androgenic alopecia Increased risk of basal cell carcinoma and pilomatrixomas
Musculoskeletal	Progressive loss of motor function Myalgias

Myotonic dystrophy

Learning objectives

Background

Etiology

Signs & symptoms

Diagnosis

Differential diagnosis

Treatment

Complications

Anesthetic management

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