Myotonic Dystrophy

Pathogenesis

• Autosomal dominant, multi-systemic disorder characterized by myotonia, muscle weakness and early-onset cataracts (before age of 50)
• Most common type is myotonic dystrophy type 1 (DM1), which is caused by an unstable, expansile CTG trinucleotide repeat in the gene myotonic dystrophy type 1 protein kinase (DMPK) on chromosome 19
  • Demonstrates anticipation – successive generations more severely affected, at a younger age; correlates with size of genetic expansion
  • Myotonia caused by reduction in synthesis of skeletal muscle chloride channel
  • Somatic mosaicism: varying phenotype
  • Disability often by age 30 – 50
• Myotonic dystrophy type 2 (DM2) caused by unstable tetranucleotide CCTG repeat expansion of the zinc finger protein 9 on chromosome 3
  • Anticipation rare
  • Disability age 65 – 80 years
  • Myalgia and tremors are very prominent symptoms (rare in DM1)

Physical signs

• Myotonic facies: wasting of the temporalis muscles, male-pattern balding, weakness of the facial muscles, smooth forehead, bilateral ptosis; hollow cheeks with a sagging jaw
• Cataracts, typically early-onset, iridescent, posterior sub-capsular
• Delayed ability to open eyes after forceful closure
• Dysarthria: say this for me: “West Register Street”
• Nasogastric feeding tube, suggesting bulbar weakness and dysphagia
• Tongue myotonia
• Weakness of sternocleidomastoid
• May have weakness of neck flexion
• Distal weakness, especially of intrinsic muscles of the hand, finger flexors, elbow extensors and ankle dorsiflexors (causing foot drop)
• Percussion myotonia: delayed relaxation following percussion of the thenar eminence
• Grip myotonia: delayed relaxation of firm handshake
• Reflexes depressed
• Gait: high steppage (foot drop)
• May have foot orthoses present
• Sensation and tone normal
• Cardiovascular:
  • Signs of implantable cardiac devices (heart block)
  • Mitral valve prolapse
  • Signs of cardiac failure (dysfunction in cardiac relaxation)
• Respiratory: signs of infection (aspiration)

 Further examination / investigation

• Gold standard for diagnosis: DNA testing on leukocytes
• Electromyography to confirm diagnosis: repetitive firing of muscle action potentials following a stimulus. Discharge classically decreases in amplitude and frequency with time
• Muscle biopsy: not necessary, may show atrophy of type 1 fibres
• Muscle enzymes usually normal or mildly raised
• Testes for testicular atrophy and gynaecomastia
  • Endocrine profile: increased luteinizing hormone and follicle-stimulating hormone; testosterone deficiency
• Fasting glucose (co-existent metabolic syndrome)
• Thyroid function (association with hypothyroidism, which can exacerbate weakness)
• Chest radiograph: cardiomegaly, signs of pneumonia
• Electrocardiogram:
  • Varying degrees of heart block (progressive conduction disturbance)
  • Tachyarrhythmias (SVT, atrial flutter / fibrillation, ventricular tachycardia)
  • Prolonged QTc
• Transthoracic echocardiogram: LVH, cardiomyopathy
• Polysomnography: daytime somnolence (nocturnal hypoventilation or central phenomenon)
• Audiometry: sensorineural hearing loss
• Gastrointestinal: constipation / diarrhoea

Management

• Multidisciplinary team approach which addresses critical symptoms, screens for asymptomatic disease and provides genetic counselling with patient education
• Genetic counselling: autosomal dominant, 50% of offspring affected; anticipation
• Preserving function: high top shoes / ankle foot orthoses for dorsiflexion weakness
  • Physiotherapy
• Myotonia: mexiletine or flecainide; phenytoin, amitriptyline, not advisable because of effects cardiac conduction system
• Annual electrocardiogram to screen for conduction defects
• Nocturnal BiPAP for nocturnal hypoventilation
• Speech therapy for dysphagia / dysarthria
• Testosterone / thyroid replacement as necessary
• Control of co-existent diabetes
• Small, low-fat meals for gastrointestinal symptoms
• Cataract surgery, eyelid taping if necessary to prevent corneal abrasions
• Anaesthesia: avoidance of depolarizing agents (paradoxical reactions)

Differential diagnosis

• Myotonia: myotonia congenita (autosomal dominant – Thomsen’s disease, early onset; Becker’s disease, later onset), paramyotonia congenita (autosomal dominant), hypokalaemic periodic paralysis, drugs (clofibrate)
• Distal wasting and weakness: hereditary motor sensory neuropathy (Charcot-Marie-Tooth), distal spinal muscular atrophy, inclusion body myositis, oculopharyngodistal myopathy

Summary

This patient has myotonic dystrophy. He has myotonic facies, with bilateral ptosis, wasting of the temporalis, massater and sternocleidomastoid muscles and frontotemporal balding. There are bilateral cataracts, and there is difficulty in opening the eyes following forced and sustained closure. In the limbs, there is distal weakness and wasting, especially of the finger flexors, intrinsic muscles of the hand and ankle dorsiflexors. This has caused a foot drop, which is being corrected with a foot orthosis. There is evidence of both grip and percussion myotonia. The deep tendon reflexes are depressed. Sensation is normal.

The pulse is regular. There is no evidence of an implantable cardiac device, which may be necessary for high-degree cardiac conduction defects or in malignant arrhythmias. There is also no evidence of a nasogastric feeding tube or a percutaneous gastrostomy, which would suggest significant dysphagia.

Given the opportunity, I would have liked to examine this patient’s testes, as well as perform a thyroid status examination.

I would like to confirm my diagnosis by demonstrating electrical myotonia with electromyography. I would like to further investigate this patient by performing an electrocardiogram to look for evidence of cardiac conduction defects. I would also like to obtain a chest radiograph to look for signs of infection, which may occur as a result of aspiration, and cardiomegaly. The fasting glucose, thyroid hormones and reproductive hormones should also be checked. I would like to offer polysomnography to screen for nocturnal hypoventilation.