DMPK, CTG expansionChromosome 3
Zinc finger protein 9, CCTGInheritanceAutosomal dominantAutosomal dominantAge of onsetInfancy – adulthood, varies with severity and number of repeatsChildhood –adulthood, varies with severity and number of repeatsTypical pattern of myopathyFace, forearms, finger flexors, distal legsNeck flexors, thighs and hips; more mild weaknessClinical myotoniaProminent, primarily hand, forearm muscles and tongue; can affect both smooth and skeletal muscleMild, primarily hands and thighs; can affect both smooth and skeletal muscle.
Patients may have atypical muscle pain

Weakness

Typically, muscle weakness in DM1 includes the facial muscles, long flexors of the fingers (flexor profundus muscles), intrinsic hand muscles, and dorsiflexors of the feet (tibialis anterior, extensor hallucis longus, and extensor digitorum longus). Less frequently, DM1 patients have proximal upper extremity weakness including the shoulder stabilizing and abduction muscles. In advanced cases, respiratory muscles may be impaired, placing patients at risk for respiratory failure and aspiration.

Myotonia

Myotonia is commonly demonstrated in the hands, forearms, and grip of patients with DM1. Often patients develop this symptom before they develop weakness and present with “locking or stiffness” of the hands. Although percussion myotonia can also be demonstrated at a patient’s tongue, this test is uncomfortable to patients and does not have obvious advantages over testing the extremities.

Cardiac Involvement

Life-threatening progressive cardiac arrhythmias and sudden death may occur in DM1. Cardiac conduction abnormalities are more likely with increased age and with more severe neuromuscular symptoms. Screening echocardiograms may reveal global diastolic dysfunction and reduced systolic function. Progressive heart block, prolongation of the QRS and P–R intervals, sinus node dysfunction, atrial or ventricular tachycardia or fibrillation, and atrial flutter occur. Higher rates of sudden death are associated with the presence of atrial tachyarrhythmias and other severe EKG abnormalities.

Gastrointestinal Symptoms

Some DM1 patients experience gastrointestinal symptoms including dysarthria, dysphagia, gastric regurgitation, constipation, diarrhea, and insulin resistance. These symptoms can be severe and cause a substantial disruption to a patient’s life.

Cognitive Symptoms

Cognition may be impaired in DM1. Impaired executive function, difficulty with visual spatial processing, depression, apathy, and avoidant personality disorders are reported. Radiologically, these symptoms may correspond with increased cerebral atrophy at the bifrontal and parietal lobes, bilateral middle temporal gyrus, and left superior and occipital gyri.

Sleep Disturbance

Excessive daytime sleepiness is seen in approximately a third of DM1 patients and tends to be proportional to the degree of weakness. In addition, patients often report excessive sleep requirements (more than 10 hours), irregular sleep patterns, extensive daytime naps, insomnia, and somnolence after meals.

Vision and Hearing

Over time cataracts develop and impede vision. Cataracts may be the initial or only findings of DM1. Patients may also develop corneal abrasions secondary to the inability to fully close their eyelids at night. Sensorineural hearing loss occurs in DM1 and may impair a patient’s ability to communicate effectively.

Laboratory Abnormalities in DM1

Multiple laboratory abnormalities are common in DM1 and reflect the multisystemic involvement. Among these, creatine kinase levels, liver function tests, and cholesterol panels often demonstrate elevated values whereas albumin, and red and white blood cell counts are frequently low.

Congenital Myotonic Dystrophy

DM1 may present as a congenital form. As CTG repeat lengths increase from one generation to the next, a parent with minimal symptoms may have a child with congenital DM1 with severe clinical features. Congenital DM1 should be considered in infants with any of the following: hypotonia, generalized weakness, respiratory failure, failure to thrive, feeding difficulties, clubfoot deformity, or a history of reduced fetal movement with polyhydramnios. Newborns with congenital myotonia do not have clinical myotonia on examination. Patients requiring prolonged ventilation have a 25% mortality rate in the first year. Congenital DM1 patients who survive may have cognitive symptoms ranging from mild learning difficulties to behavioral issues to severe learning difficulties. Although some patients experience both physical and cognitive improvement during childhood, the progressive weakness and symptoms consistent with adult-onset DM1 may occur and progress in the second and third decades.

Myotonic Dystrophy Type 2

MD2 (also referred to as proximal myotonic myopathy) typically presents in adulthood, usually between 20 and 75 years of age. As with DM1, the cardinal symptoms of DM2 are early cataracts (age <50 years), weakness, and myotonia; however, in comparison with DM1, DM2 may have a more benign phenotype with less widespread weakness, muscle atrophy, and lower rates of systemic complications (see Table 10.1). Patients with an early age of onset are more likely to have more severe weakness and a broader spectrum of symptoms. In contrast to DM1, DM2 patients tend to experience more proximal extremity pain and stiffness with variable degrees of clinical myotonia.

Weakness

The distribution of weakness in DM2 is more proximal than in DM1 and often involves the neck flexors, hip flexors, hip extensors, and long flexors of the fingers. In general, facial weakness and muscle wasting are not as severe as in DM1, although some patients may experience mild hypertrophy at their gastrocnemius muscles.

Myotonia

The presence of myotonia may be tested for and detected in DM2. In late-onset DM2 cases, myotonia may be present only electrodiagnostically, or may be absent entirely.

Pain

Pain is a prominent and disabling feature in DM2. Patients often describe this symptom as cramping, stiffness, or an aching sensation that fluctuates in intensity and distribution over the limbs. Occasionally this symptom is inappropriately attributed to sciatica, fibromyalgia, or a statin-induced myopathy while exacerbating factors may include exercise, palpation, and temperature.