Huntington's disease-like syndromes (HD-like syndromes, or HDL syndromes) are a family of inherited

neurodegenerative diseases A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

that closely resemble

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...

(HD) in that they typically produce a combination of chorea, cognitive decline or

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

and behavioural or psychiatric problems.

Types

HDL1

HDL1 is an unusual,

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

familial

prion disease Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It i ...

. Only described in one family, it is caused by an eight- octapeptide repeat insertion in the ''

PRNP Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...

'' gene. More broadly, inherited prion diseases in general can mimic HD.

HDL2

HDL2 is the most common HD-like syndrome and is caused by CTG/ CAG triplet expansions in the ''

JPH3 Junctophilin-3 is a protein that in humans, is encoded by the ''JPH3'' gene. The gene is approximately 97 kilobases long and is located at position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexe ...

'' 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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

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

Other

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 C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene ''C9orf72''. The human ''C9orf72'' gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pai ...

'', spinocerebellar ataxias type 1 and 3, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea,

Friedreich's ataxia Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 year ...

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

References

External links

{{Medical resources , DiseasesDB = 33520, 33521, 34626 , OMIM = 606438, 603218, 604802 Rare syndromes Extrapyramidal and movement disorders Genetic diseases and disorders Systemic atrophies primarily affecting the central nervous system Autosomal dominant disorders Trinucleotide repeat disorders Huntington's disease