Abstract

The Huntington's disease-like syndromes (often abbreviated as HD-like or "HDL" syndromes) are a family of inherited neurodegenerative diseases that closely resemble Huntington's disease (HD) in that they typically produce a combination of chorea, cognitive decline or dementia and behavioural or psychiatric problems.

HDL1

HDL1 is an unusual, autosomal dominant familial prion disease. Only described in one family, it is caused by an eight-octapeptide repeat insertion in the "PRNP" gene. More broadly, inherited prion diseases in general can mimic HD.

HDL2

HDL2 is the commonest HD-like syndrome and is caused by GTC/CAG triplet expansions in the

"JPH3" gene encoding junctophilin-3. It is almost exclusively restricted to populations of African descent, and is actually more common than Huntington’s disease in black South Africans.

HDL3

HDL3 is a rare, autosomal recessive disorder linked to chromosome 4p15.3. It has only been reported in two families and the causative gene is unidentified.

Other causes of HD-like syndromes

Other neurogenetic disorders can cause an HD-like or HD phenocopy syndrome but are not solely defined as HDL syndromes. The commonest is spinocerebellar ataxia type 17 (SCA-17), occasionally called HDL-4. Others include mutations in "C9orf72", spinocerebellar ataxias type 1 and 3, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia, mitochondrial disease.

A Huntington's disease-like presentation may also be caused by acquired causes.