Phenotypic expression of Huntington’s disease varies by presence of motor, cognitive, and psychiatric symptoms. Psychiatric and cognitive abnormalities can predate the motor abnormality by at least 15 years. Initial symptoms requiring care often include irritabity, anxiety, or depressed mood. Other behavioral disturbances may include pronounced ap- athy, disinhibition, impulsivity, and impaired insight, with apathy often becoming more progressive over time. Early movement symptoms may involve the appearance of fidget- iness of the extremities as well as mild apmxia (i.e., difficulty with purposeful movements), particularly with fine motor tasks. As the disorder progresses, other motor problems in- clude impaired gait (ataxia) and postural instability. Motor impairment eventually affects speech production (dysarthria) such that the speech becomes very difficult to understand, which may result in significant distress resulting from the communication barrier in the context of comparatively intact cognition. Advanced motor disease severely affects gait with progressive ataxia. Eventually individuals become nonambulatory. End-stage motor disease impairs motor control of eating and swallowing, typically a major contributor to the death of the individual from aspiration pneumonia.
Genetic and physiological. The genetic basis of Huntington’s disease is a fully penetrant autosomal dominant expansion of the CAG trincleotide, often called a CAG repeat in the huntingtin gene. A repeat length of 36 or more is invariably associated with Huntington’s disease, with longer repeat lengths associated with early age at onset. A CAG repeat length of 36 or more is invariably associated with Huntington’s disease.
Genetic testing is the primary laboratory test for the determination of Huntington’s dis- ease, which is an autosomal dominant disorder with complete penetrance. The trinucleo- tide CAG is observed to have a repeat expansion in the gene that encodes huntingtin protein on chromosome 4. A diagnosis of Huntington’s disease is not made in the presence of the gene expansion alone, but the diagnosis is made only after symptoms become man- ifest. Some individuals with a positive family history request genetic testing in a presymp- tomatic stage. Associated features may also include neuroimaging changes; volume loss in the basal ganglia, particularly the caudate nucleus and putamen, is well known to occur and progresses over the course of illness. Other structural and functional changes have been observed in brain imaging but remain research measures.
Functionai Consequences of Major or Mild
Neurocognitlve Disorder Due to Huntington’s Disease
In the prodromal phase of illness and at early diagnosis, occupational decline is most com— mon, with most individuals reporting some loss of ability to engage in their typical work.
The emotional, behavioral, and cognitive aspects of Huntington’s disease, such as disin- hibition and personality changes, are highly associated with functional decline. Cognitive deficits that contribute most to functional decline may include speed of processing, initi- ation, and attention rather than memory impairment. Given that Huntington’s disease on- set occurs in productive years of life, it may have a very disruptive effect on performance in the work setting as well as social and family life. As the disease progresses, disability from problems such as impaired gait, dysarthria, and impulsive or irritable behaviors may substantially add to the level of impairment and daily care needs, over and above the care needs attributable to the cognitive decline. Severe choreic movements may substantially interfere with provision of care such as bathing, dressing, and toileting.
Other mental disorders. Early symptoms of Huntington’s disease may include instabil- ity of mood, irritability, or compulsive behaviors that may suggest another mental disor- der. However, genetic testing or the development of motor symptoms will distinguish the presence of Huntington’s disease.