A 35-Year-Old Man With Involuntary Movement and Depression

Niranjan N. Singh, MBBS, MD, DM

Disclosures

November 22, 2017

Discussion

This 35-year-old man has Huntington disease. He has insidious-onset, slowly progressive movement disorder, and movements are absent during sleep. His movements are described as choreoathetoid. He has family history that suggests autosomal dominant transmission. Apart from the movement disorder, he also has neuropsychiatric manifestations, with early death in the family due to depression. A CT scan of the head revealed evidence of caudate nucleus atrophy. Brain MRI revealed evidence of caudate atrophy (Figure).

Figure.

Regarding the differential diagnoses, he has no history of antipsychotic medication use, which can lead to tardive dyskinesia. He has no history of infection or diagnostic evidence that suggested heart involvement. He had no ECG changes or abnormalities on transthoracic echocardiography, as is seen in patients with Sydenham chorea. His family history is negative for Sydenham chorea. No acanthocytes were noted.

Huntington disease is a rare neurodegenerative disorder of the central nervous system (CNS) characterized by choreiform movements, behavioral and psychiatric disturbances, and dementia.[1]Huntington disease is caused by an autosomal-dominantly inherited expansion of CAG trinucleotide repeats in the huntingtin (HTT) gene on chromosome 4; this leads to production of a mutant huntingtin (mHTT) protein, with an abnormally long polyglutamine repeat.[2]Individuals with more than 39 CAG repeats develop the disease, whereas reduced penetrance is seen in those with 36-39 CAG repeats. The disease can be anticipated when the gene is passed down the paternal line, as in this case; a father with a CAG repeat length in the intermediate range may have a child with an expanded pathogenic repeat length. This is because sperm from males shows greater repeat variability and larger repeat sizes than somatic tissues. Mutant huntingtin protein leads to death and neuronal dysfunction through various mechanisms. Postmortem studies reveal diffuse atrophy of the caudate and putamen.

Prevalence in the white population is estimated at 1 in 10,000 to 1 in 20,000. The mean age at symptom onset is 30-50 years. In some cases, symptoms begin before age 20 years, with behavior disturbances and learning difficulties at school; this is termed juvenile Huntington disease (Westphal disease).[3]The first description, by Waters, dates to 1842. However, after a description in 1872 by George Huntington, it became known as Huntington chorea. In 1983, a linkage on chromosome 4 was established, and in 1993 the gene for Huntington disease was found.[1]

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