The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test

@article{Schneider2007TheHD,
  title={The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test},
  author={Susanne A Schneider and Ruth H Walker and Kailash P. Bhatia},
  journal={Nature Clinical Practice Neurology},
  year={2007},
  volume={3},
  pages={517-525}
}
Huntington's disease (HD), which is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD), accounts for about 90% of cases of chorea of genetic etiology. In recent years, several other distinct genetic disorders have been identified that can present with a clinical picture indistinguishable from that of HD. These disorders are termed Huntington's disease-like (HDL) syndromes. So far, four such conditions have been recognized, namely disorders attributable to… 
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PURPOSE OF REVIEW The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's
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TLDR
The present finding may be incidental, however, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions, and is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.
Autopsy‐proven Huntington's disease with 29 trinucleotide repeats
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    Movement disorders : official journal of the Movement Disorder Society
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TLDR
This case raises the possibility that another explanation for the low number of CAG repeats in an otherwise typical case of HD is that the low limit needed for the diagnosis of HD may need to be modified, and suggests that the rather arbitrarily defined low limit of C AG repeat number should be reexamined.
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This research demonstrates that nuclear localization of the polyglutamine protein is critical to disease pathogenesis in HDL2, but not HD, and concludes that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms contribute to the two neurodegenerative disorders.
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TLDR
The most likely remote ethnic origin for all detected families was African, and HDL2 in Venezuela had a low, but higher relative frequency than that in other Caucasoid populations.
Re: Autopsy‐proven Huntington's disease with 29 trinucleotide repeats
TLDR
This case raises the possibility that another explanation for the low number of CAG repeats in an otherwise typical case of HD is that the low limit needed for the diagnosis of HD may need to be modified, and suggests that the rather arbitrarily defined low limit of C AG repeat number should be reexamined.
expansions are the most common genetic cause of Huntington ’ s disease phenocopies
TLDR
This study extends the known phenotype of the C9orf72 expansion, both in age of onset and movement disorder symptoms, and proposes a revised clinico-genetic algorithm for the investigation of HD-phenocopy patients based on these data.
Reply: Autopsy‐proven Huntington's disease with 29 trinucleotide repeats
TLDR
This case raises the possibility that another explanation for the low number of CAG repeats in an otherwise typical case of HD is that the low limit needed for the diagnosis of HD may need to be modified, and suggests that the rather arbitrarily defined low limit of C AG repeat number should be reexamined.
Huntington's disease-like disorders in Latin America and the Caribbean.
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References

SHOWING 1-10 OF 81 REFERENCES
Huntington's disease like-2: review and update.
TLDR
The phenotypic similarities between HD and HDL2 suggest that understanding the pathobiology of HDL2 may shed new light on the pathogenesis of HD and other disorders of striatal neurodegeneration.
Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes.
TLDR
A group of 252 patients with a Huntington's disease-like (HDL) phenotype, including 60 with typical Huntington’s disease, who had tested negative for pathological expansions in the IT15 gene are reported, to report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs.
Huntington's disease–like 2 (HDL2) in North America and Japan
TLDR
The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD‐like phenotype.
Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington’s disease-like phenotype
TLDR
Several families have been reported with clinical features closely resembling HD and autosomal dominant inheritance, among these, an early-onset non-progressive chorea with benign course has been associated with mutations in TITF-1 mapped.
Huntington disease phenocopy is a familial prion disease.
TLDR
It is argued that clinicians should consider screening for PrP mutations in individuals with HD-like diseases in which the characteristic HD (CAG)n repeat expansions are absent and raises the possibility that an unknown number of HD phenocopies are familial prion diseases.
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion
TLDR
A large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation is reported, which is termed Huntington's disease‐like 2 (HDL2), and may yield valuable insight into the pathogenesis of HD and related disorders.
A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.
TLDR
To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide, and tetranucleotide-repeat DNA markers was performed and indicated that the gene responsible for the disease is likely located in a 2.7-cM region.
Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3.
TLDR
The inheritance pattern and unique localization to 4p15.3 are consistent with the identification of a novel, autosomal recessive, neurodegenerative Huntington-like disorder.
Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype
TLDR
The genetic analysis of 107 Portuguese patients with an HDL phenotype found none of the genes already included in the differential diagnosis of HD was responsible for the disease in this sample, so the genetic heterogeneity of the HDL phenotype is still open for investigation.
Huntington's disease like‐2 neuropathology
TLDR
Pathologically, HDL‐2 is similar to HD in its effect on the neostriatum but may differ, at least in some cases, in its degree of focal cortical involvement, including the occipital lobe.
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