640 Neurocognitive Disorders
which may result in significant distress resu lting 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.
Risk and Prognostic Factors 
Genetic and physiological. The genetic basis of Huntington’s disease is a fully penetrant
autosomal dominant expansion of th e 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 asso ciated with Huntington’s disease.
Diagnostic Markers
Genetic testing is the primary laboratory test  for the determination of Huntington’s dis-
ease, which is an autosomal dominant disord er with complete penetrance. The trinucleo-
tide CAG is observed to have a repeat ex pansion in the gene that encodes huntingtin
protein on chromosome 4. A di agnosis of Huntington’s disease is not made in the presence
of the gene expansion alone, but the diagno sis is made only after symptoms become man-
ifest. Some individuals with a positive family  history request genetic testing in a presymp-
tomatic stage. Associat ed features may also include neur oimaging changes; volume loss in
the basal ganglia, particularly the caudate nu cleus and putamen, is well known to occur
and progresses over the course of illness. Other structural and functional changes have
been observed in brain imagin g but remain research measures.
Functional Consequences of Major or Mild