Huntington's disease-like syndrome
{{Infobox medical condition (new)
| name = Huntington's disease-like syndrome
| synonyms = HDL syndrome
| field = Neurology
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Huntington's disease-like syndromes (HD-like syndromes, 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.{{cite journal|last1=Wild|first1=EJ|last2=Tabrizi|first2=SJ|title=Huntington's disease phenocopy syndromes.|journal=Current Opinion in Neurology|date=December 2007|volume=20|issue=6|pages=681–7|pmid=17992089|doi=10.1097/wco.0b013e3282f12074|s2cid=37287959}}
Types
= 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 most common HD-like syndrome and is caused by CTG/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. Full penetrance occurs in people with 40 repeats or more. A South African study in 2024 examined eight individuals with HDL2 and found their repeat numbers varied from 45 to 63, with the median number being 52. The same study found that increasing repeat number is correlated with greater cognitive and behavioural impairment, but less chorea.{{Cite journal |last1=Narotam-Jeena |first1=Heena |last2=Guttman |first2=Mark |last3=van Hillegondsberg |first3=Ludo |last4=van Coller |first4=Riaan |last5=Krause |first5=Amanda |last6=Carr |first6=Jonathan |date=2024 |title=Atypical Presentations of Huntington Disease-like 2 in South African Individuals |journal=Movement Disorders Clinical Practice |language=en |volume=11 |issue=7 |pages=850–854 |doi=10.1002/mdc3.14052 |issn=2330-1619 |pmc=11233840 |pmid=38725192}}
= 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 =
Other neurogenetic disorders can cause an HD-like or HD phenocopy syndrome but are not solely defined as HDL syndromes. The most common is spinocerebellar ataxia type 17 (SCA-17), occasionally called HDL-4. Others include mutations in C9orf72,{{cite journal|last1=Hensman Moss|first1=DJ|last2=Poulter|first2=M|last3=Beck|first3=J|last4=Hehir|first4=J|last5=Polke|first5=JM|last6=Campbell|first6=T|last7=Adamson|first7=G|last8=Mudanohwo|first8=E|last9=McColgan|first9=P|last10=Haworth|first10=A|last11=Wild|first11=EJ|last12=Sweeney|first12=MG|last13=Houlden|first13=H|last14=Mead|first14=S|last15=Tabrizi|first15=SJ|title=C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies.|journal=Neurology|date=28 January 2014|volume=82|issue=4|pages=292–9|pmid=24363131|doi=10.1212/WNL.0000000000000061|pmc=3929197}}{{cite journal|last1=Cooper-Knock|first1=J|last2=Shaw|first2=PJ|last3=Kirby|first3=J|title=The widening spectrum of C9ORF72-related disease; genotype/phenotype correlations and potential modifiers of clinical phenotype.|journal=Acta Neuropathologica|date=March 2014|volume=127|issue=3|pages=333–45|pmid=24493408|doi=10.1007/s00401-014-1251-9|pmc=3925297}} spinocerebellar ataxias type 1 and 3, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia and mitochondrial diseases.
A Huntington's disease-like presentation may also be caused by acquired causes.
References
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External links
{{Medical resources
| DiseasesDB = 33520, 33521, 34626
| OMIM = 606438, 603218, 604802
}}
Category:Extrapyramidal and movement disorders
Category:Systemic atrophies primarily affecting the central nervous system
Category:Autosomal dominant disorders