Huntington's disease-like
Huntington's disease-like (HDL) is a group of rare neurological conditions that resemble Huntington's disease, characterized by uncontrolled movements, emotional problems, and a decline in thinking ability.
Overview
HDLs occur in people who display the characteristic features of Huntington's disease but do not have a variant in the gene typically associated with that disorder. Researchers have described four types, designated HDL1 through HDL4. Sometimes, HDL4 is also known as spinocerebellar ataxia type 17 (SCA17).
Symptoms
HDL1, HDL2, and HDL4 usually begin in early to mid-adulthood. Common symptoms include:
- Irritability and emotional problems
- Small involuntary movements (dyskinesia)
- Poor coordination and trouble learning or making decisions
- Chorea (involuntary jerking or twitching movements)
- Problems with walking (bradykinesia), speaking (dysarthria), and swallowing (dysphagia)
- Changes in personality and decline in thinking abilities (dementia)
HDL3 begins much earlier in life, usually around age 3 or 4, and is characterized by a decline in thinking ability, movement and speech difficulties, and seizures.
Causes
Variants in the PRNP, JPH3, and TBP genes cause the various HDLs. These genes provide instructions for making proteins important for normal brain function. The variants involve an increase in the length of repeated DNA segments, leading to the production of abnormal proteins that build up in neurons and disrupt their function.
Genes Associated with Huntington's disease-like
- JPH3
- PRNP
- TBP
Inheritance
HDL1, HDL2, and HDL4 are inherited in an autosomal dominant pattern, meaning one copy of the altered gene is sufficient to cause the disorder. HDL2 and HDL4 often exhibit anticipation, where the condition begins earlier and symptoms become more severe in successive generations. HDL3 is likely inherited in an autosomal recessive pattern, requiring two copies of the altered gene.
