Name: SKY-0515 in Huntington's disease: Clinical presentation - signs and symptoms
Published: 2026-09-16T18:00:43-04:00

Motor symptoms: chorea

“Chorea, an involuntary movement disorder consisting of nonrepetitive, nonperiodic jerking of limbs, face, or trunk, is the major sign of HD. Chorea is present in most individuals and typically increases in severity during the first ten years.” (opens the source at this quote in a new tab)

Motor symptoms: dystonia, bradykinesia, rigidity, and oculomotor disturbance

“With advancing disease duration, chorea may decrease and other movement abnormalities such as bradykinesia, rigidity, and dystonia occur. Impairment in voluntary motor function is an early sign.” (opens the source at this quote in a new tab)
“Difficulty in initiating ocular saccades, slow and hypometric saccades, and problems in gaze fixation occur in up to 75% of symptomatic individuals” (opens the source at this quote in a new tab)

“Early in the disease, they are primarily hyperkinetic with involuntary chorea. In later stages, however, hypokinesia with bradykinesia and dystonia may predominate.” (opens the source at this quote in a new tab)

Motor symptoms: gait disturbance and falls

“Compared to controls, Huntington patients had a decreased gait velocity (1.15 m/s versus 1.45 m/s, P < 0.001) and a decreased stride length (1.29 m versus 1.52 m, P < 0.001).” (opens the source at this quote in a new tab)

Cognitive symptoms: executive dysfunction and progressive decline

“A global and progressive decline in cognitive capabilities occurs in all individuals with HD. Cognitive changes include forgetfulness, slowness of thought processes, impaired visuospatial abilities, and impaired ability to manipulate acquired knowledge” (opens the source at this quote in a new tab)
“These initial changes often involve loss of mental flexibility and impairment of executive functions such as mental planning and organization of sequential activities.” (opens the source at this quote in a new tab)

“Chorea and other aspects of the movement disorder are the most visible aspect of the disease. However, non-motor features have greatest affect on functional independence and quality of life, so require recognition and management.” (opens the source at this quote in a new tab)

Psychiatric symptoms: depression, irritability, apathy, and anxiety

“Ninety eight per cent of the patients exhibited neuropsychiatric symptoms, the most prevalent being dysphoria, agitation, irritability, apathy, and anxiety.” (opens the source at this quote in a new tab)

“Depression is the most common psychiatric manifestation, affecting 40% of individuals with HD, followed by anxiety” (opens the source at this quote in a new tab)
“Apathy is a common and disabling symptom that is related to disease stage and worsens with progression” (opens the source at this quote in a new tab)

“Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients.” (opens the source at this quote in a new tab)

Psychiatric symptoms: suicidality

“Eleven (20%) pre-motor and 20 (20%) motor symptomatic mutation carriers were considered suicidal compared to none of the non-carriers.” (opens the source at this quote in a new tab)

Other symptoms: weight loss

“Individuals with HD tend to experience substantial weight loss, reduced muscle mass, and lower body mass index compared to unaffected individuals.” (opens the source at this quote in a new tab)
“Individuals usually have very high calorie requirements to simply maintain their weight.” (opens the source at this quote in a new tab)

Other symptoms: dysarthria and dysphagia

“Speech impairment reflects a combination of dysarthria and word-finding difficulties, and in advanced disease some individuals may progress to complete anarthria. Swallowing difficulties arise from incoordination of oral and pharyngeal muscles, and can lead to choking episodes and aspiration pneumonia, a frequent cause of death in HD.” (opens the source at this quote in a new tab)

Other symptoms: sleep and circadian disturbance

“The most common sleep problems reported by HD patients include insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness.” (opens the source at this quote in a new tab)

Juvenile Huntington's disease: presentation

“In the first decade of life, individuals with juvenile HD present with common clinical manifestations of behavior disturbance and impairment of school performance, followed by dysarthria, seizures, rigidity, gait disturbances, bradykinesia, and dystonia” (opens the source at this quote in a new tab)

“Seizures occur in 30 percent to 50 percent of children with this condition.” (opens the source at this quote in a new tab)