A 28-year-old woman comes to the office due to stiffness and weakness of her hands over the past several months. The patient has had decreased grip strength and frequent episodes in which her hands felt so stiff that she could not let go of objects. She also reports fatigue and excessive sleepiness and says, "I can sleep 20 hours straight and still wake up tired." The patient has had occasional difficulty with speech, which she describes as mild slurring and a heavy feeling in the tongue. She has no prior medical conditions and takes no medications. Vital signs are within normal limits. Physical examination shows a flat affect and mild bilateral ptosis. Hand grip is weak bilaterally, and mild atrophy of the small muscles of the hands is present. Deep tendon reflexes are normal throughout and Babinski sign is absent. When the patient is instructed to repeatedly close the eyes tightly, there is a noticeable lag when she opens them. Which of the following is the most likely cause of this patient's current condition?
Myotonic dystrophy | |
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This young woman with hand stiffness and muscle atrophy associated with a flat affect, ptosis, and dysarthria has findings suggestive of myotonic dystrophy (MD). MD is a multisystem autosomal dominant disorder most commonly caused by the expansion of cytosine-thymine-guanine (CTG) trinucleotides in the dystrophia myotonica protein kinase (DMPK) gene. In most patients, MD presents in late adolescence or early adulthood; however, the CTG repeat length correlates with an earlier age of onset, and those with the highest repeat burden may develop symptoms in childhood (eg, childhood/infantile form).
MD is characterized by myotonia (delayed muscle relaxation after contraction) with progressive muscle atrophy and weakness. Findings of classic MD reflect the involvement of different muscle groups:
Other common associated features, reflecting involvement of systems other than muscular system, include cataracts, testicular atrophy, and sleep disturbances (eg, hypersomnia, excessive daytime sleepiness). Genetic testing confirms the diagnosis. Management is supportive and prognosis is poor, with most patients dying from respiratory failure or cardiac arrhythmias at approximately age 40-50.
(Choice A) Hyperthyroidism can cause progressive myopathy and may be associated with lid lag. However, weakness is most prominent in the proximal muscles (eg, hip flexors, quadriceps) rather than in the distal muscles, as seen in MD. Myotonia is atypical. In addition, symptoms of hyperthyroidism (eg, heat intolerance, palpitations) are expected.
(Choice B) Myasthenia gravis, which is caused by anti–acetylcholine receptor antibodies, can cause weakness that is prominent in the facial/bulbar musculature; however, the weakness is fluctuating, fatigable, and most prominent in the proximal muscles (eg, shoulders, neck). Prominent distal weakness and myotonia are atypical.
(Choice D) Inflammatory myopathies (eg, polymyositis) are characterized by lymphocytic inflammation of the skeletal muscle. However, weakness is typically worse in the proximal musculature and myotonia is unexpected.
(Choice E) Systemic sclerosis (scleroderma) is caused by progressive fibrosis of multiple organs. Although skin thickening can cause difficulty with grasping, myotonia is unexpected. In addition, skin thickening, digital tip ulcerations, and telangiectasias are typically visible on examination.
Educational objective:
Myotonic dystrophy is an autosomal dominant disorder caused by the expansion of cytosine-thymine-guanine trinucleotides. The disease typically presents in late adolescence or early adulthood with facial and distal muscle weakness and myotonia (delayed muscle relaxation after contraction); cataracts, testicular atrophy, and sleep disturbances are also common.