A 45-year-old woman comes to the office for evaluation of forgetfulness and difficulty with concentration. The patient has depression diagnosed 6 months ago and takes sertraline, which has not improved her mood symptoms. She says, "Now I'm missing deadlines and forgetting important things at work. This has never been a problem for me before." The patient has no suicidal ideation or hallucinations. Medical history is otherwise noncontributory, and she takes no other medications. Temperature is 36.9 C (98.4 F), blood pressure is 122/80 mm Hg, pulse is 64/min, and respirations are 14/min. On physical examination, the patient appears restless, crossing and uncrossing her arms and legs and shifting her weight while seated. Her facial expressions change abruptly throughout the evaluation. The patient is unable to maintain a firm grasp on grip testing. Muscle strength and tone are normal in the upper and lower extremities. Gait is normal. She is fully oriented but scores 24/30 on the Montreal Cognitive Assessment (normal: ≥26), losing points on tests of executive function and memory. Which of the following is the most likely diagnosis?
Huntington disease | |
Clinical features |
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Findings |
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Management & prognosis |
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Huntington disease (HD) causes a progressive functional deterioration due to an autosomal dominant CAG trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p. Neuronal cell death in the caudate nucleus and putamen leads to a combination of symptoms, including:
Chorea is a core feature of HD and is characterized by sudden involuntary movements of the face, limbs, and trunk. Early, it may include milder manifestations that look like restlessness or fidgeting (eg, crossing and uncrossing arms and legs) and can be overshadowed by more pronounced psychiatric features (eg, depression). Other neurologic findings include hyperreflexia and motor impersistence (eg, unable to maintain a firm grasp).
There is no cure or disease-modifying therapy, and HD is inevitably fatal; death usually occurs 10-20 years following initial symptom onset. Treatment is focused on supportive management to improve quality of life. When known, positive family history, especially for paternal transmission, is concerning for development of progressively worse and earlier presentations in children (ie, genetic anticipation).
(Choice A) Sertraline toxicity can present with neurologic (eg, hyperreflexia, tremor, clonus) and cognitive (eg, confusion, agitation, somnolence) symptoms; however, chorea would not be expected.
(Choice B) Creutzfeldt-Jakob disease (CJD) can initially present with impaired concentration and memory. However, in contrast to this patient, persons with CJD typically have startle myoclonus, ataxia, and signs of spasticity or rigidity during grip testing.
(Choice C) Dementia with Lewy bodies presents with dementia plus parkinsonism, hallucinations, and/or fluctuating cognition. This patient does have cognitive decline; however, the abrupt movements and restlessness while seated are more consistent with chorea than with parkinsonism.
(Choice D) Frontotemporal dementia presents with executive dysfunction and apathy that can look like depression; however, disinhibition, compulsive behaviors, and/or hyperorality is expected as well.
Educational objective:
Huntington disease is a highly heritable progressive illness that presents with a combination of psychiatric (eg, depression), cognitive (eg, executive impairment, memory loss), and neurologic (eg, chorea) symptoms.