Ms. A’s history is highly suggestive of Huntington’s disease. She exhibits classic motor signs, including involuntary choreiform movements in her extremities. She also has psychiatric symptoms that are commonly associated with Huntington’s disease, including depression—which preceded her motor symptoms—cognitive decline, apathy, and psychotic symptoms. In addition, her MRI findings of volume changes in the caudate nucleus and the putamen and inability to rule out a family history make Huntington’s disease more likely (Box).1,8-11
Huntington’s disease: Genetic abnormalities lead to psychiatric and neurologic symptoms
Huntington’s disease is an autosomal dominant disorder characterized by progressive motor, cognitive, and psychiatric disturbances and is the most common genetic cause of chorea. The underlying genetic mutation is a CAG repeat expansion in the Huntington’s disease gene. A Huntington’s disease diagnosis generally is considered in the presence of the characteristic choreiform movements and slowly progressive cognitive decline.8 Physical symptoms can present at any age, although they usually begin between age 35 and 44. In early stages of the disease, patients may experience subtle changes in personality, cognition, and physical skills. Although most Huntington’s disease patients eventually exhibit similar physical symptoms, the onset, progression, and extent of cognitive and psychiatric symptoms vary among individuals. However, psychiatric symptoms frequently are present during the early stages of the disease, often before motor symptoms begin and can include personality changes, irritability, agitation, apathy, and depression. In addition, up to 23% of patients with Huntington’s disease develop psychotic symptoms.1,9 There is no cure for Huntington’s disease, and mean disease duration is 17 to 20 years. The most common cause of death among Huntington’s disease patients is pneumonia, followed by suicide.1
A Huntington’s disease diagnosis is based on clinical symptoms and signs in an individual who has a parent with proven Huntington’s disease and is confirmed by DNA tests.1 Typical neuroanatomic findings include initial neuronal loss in the striatum followed by a diffuse involvement of cortical and subcortical areas.10 Volume changes in the caudate nucleus and the putamen may be a reliable measure of Huntington’s disease and potentially serve as a biomarker.11
Psychiatric symptoms
Psychiatric symptoms frequently are evident in the early stages of Huntington’s disease, often before onset of motor symptoms.1 Depression is the most common sign, and can be difficult to diagnose because weight loss, apathy, and inactivity also occur in Huntington’s disease. Feelings of low self-esteem, guilt, and anxiety can help distinguish depression from symptoms of Huntington’s disease. Cognitive decline also may present before the first motor symptoms occur. Cognitive changes typically are related to executive functions and affected individuals may develop impairments in organization and planning. Psychotic symptoms may be present, but are more common in later stages of the disease.1
Ms. A reported that quetiapine seemed to lessen her choreiform movements, and dopamine receptor blocking agents (ie, antipsychotics) often are considered for managing chorea and psychosis in Huntington’s disease. However, there are few double-blind, placebo-controlled studies evaluating the efficacy of these agents.12 Small, uncontrolled, nonrandomized trials found quetiapine has some efficacy for both motor and psychiatric symptoms in Huntington’s disease.12-15
OUTCOME: Lost to follow-up
Ms. A is discharged from the hospital 3 days after she delivers her daughter and is given an appointment in 6 weeks at an affiliated movement disorders clinic. Before discharge, she is tested for the Huntington’s disease gene mutation with a plan to receive her results during her follow-up visit. During the informed consent process for the genetic testing, Ms. A states that she was tested previously and was quite sure that the test was positive for Huntington’s disease, although she could not recall where or when this testing was completed.
Ms. A also is scheduled to follow up with her obstetrician for a 6-week postpartum check-up and tubal ligation. We encourage Ms. A to make an appointment with her psychiatrist soon after discharge. We also make a referral to the Department of Family and Children Services to provide adequate support and resources to her and her children because of her physical and psychiatric issues.
Ms. A does not show up for her follow-up appointment at the movement disorders clinic. The genetic test is not completed during this admission because of a clerical error, and the serum sample subsequently expires.