A 30-year-old man comes to the office due to lower extremity muscle pain and weakness. The patient tripped and fell while climbing stairs yesterday. He has had pain in both legs, usually with activity but occasionally at rest. The patient works as a repair person and has been having a hard time performing routine tasks such as fixing doorknobs or chandeliers. He is sexually active but has had decreased libido. The patient has had no double vision or paresthesia. He has no chronic medical conditions and takes no medications. The patient does not use tobacco, alcohol, or recreational drugs. Family history is significant for sudden cardiac death due to an arrhythmia in his father. Vital signs are normal. Examination shows a long, narrow face; the cheeks are hollowed and the jaws sag. The small muscles of the hands and dorsal flexors of the foot are weak bilaterally. Percussion over the thenar eminence displays thumb abduction and delayed relaxation. Deep tendon reflexes are 2+. Gait is unsteady. The testicles are small in volume. Which of the following is most likely to reveal the diagnosis of this patient?
Myotonic dystrophy | |
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CTG = cytosine-thymine-guanine. | |
This patient's muscle pain, weakness, and delayed relaxation are concerning for myotonic dystrophy. Myotonic dystrophy is an autosomal dominant disorder in which a trinucleotide (CTG) repeat in the DMPK gene is transcribed into untranslatable mRNA that is toxic to cellular function. Longer repeat expansion generally correlates with an earlier onset of more severe disease (ie, anticipation).
Presentation classically involves muscle weakness, pain, and atrophy, particularly in the distal (eg, hands, feet) and facial (eg, long and narrow face, sagging jaw, hollow cheeks) muscles; footdrop may result in frequent falls and an unsteady gait. Myotonia is a characteristic feature and can be elicited by percussion of the thenar eminence, which results in thumb abduction followed by delayed relaxation (percussion myotonia), or by sustained muscle contraction after the release of a handshake (grip myotonia). Involvement of cardiac muscles can result in cardiomyopathy or arrhythmias, and sudden cardiac death in this patient's father raises suspicion for undiagnosed myotonic dystrophy. Nonmuscular manifestations can include hypogonadism with decreased libido and testicular atrophy, as seen in this patient.
The diagnosis is suspected based on clinical findings and family history, and DMPK genetic testing is confirmatory. Management, including physiotherapy for weakness and testosterone replacement for symptomatic hypogonadism, is generally supportive.
(Choice A) Antinuclear antibodies are frequently positive with inflammatory myopathies (eg, polymyositis); however, proximal, not distal, muscle weakness predominates in these conditions, and myotonia and hypogonadism would not be expected.
(Choice B) In myotonic dystrophy, ECG and echocardiographic findings (eg, atrial fibrillation/flutter, atrioventricular block, left ventricle dysfunction) are nonspecific, making genetic testing to confirm the diagnosis the priority. Hypertrophic cardiomyopathy (eg, left ventricular outflow tract obstruction on echocardiography) could explain a family history of sudden cardiac death but is not classically associated with myotonia.
(Choice D) Karyotype analysis is diagnostic of Klinefelter (XXY) syndrome, which is a cause of primary hypogonadism but is not associated with muscle pain/weakness or myotonia.
(Choice E) Nerve conduction studies are helpful in evaluating weakness due to peripheral neuropathies. However, peripheral neuropathies do not cause percussion myotonia and would not explain this patient's testicular atrophy.
Educational objective:
Myotonic dystrophy is an autosomal dominant disorder characterized by myotonia, as well as pain and weakness of the distal and facial muscles. Cardiac arrythmias and hypogonadism are also common features, and genetic testing detecting the presence of a trinucleotide (CTG) repeat expansion in the DMPK gene confirms the diagnosis.