Highlights
- •We describe the larger series of clinical cases (n = 14) with HD-like phenotype and IAs published to date.
- •MRI and FDG-PET neuroimaging findings compatible with HD can be found in some patients with IA.
- •Larger and more detailed series are needed to assess the pathogenic role of IAs in HTT gene.
Abstract
Background
Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They
are present in the general population but there is an increasing number of cases with
Huntington-like phenotype reported.
Methods
We reviewed the medical records of cases in our centre where the neurologist suspected
Huntington's disease (HD) as one of the feasible diagnoses and genetic testing showed
the number of CAG repeats was in the “intermediate range”. We gathered the type of
symptoms in all cases and the main neuroimaging findings when available.
Results
We found 14 cases, 8 males and 6 females, with average age at onset at 64 years old.
Most cases exhibited some type of extrapyramidal symptoms. Cognitive and/or behavioral
symptoms were also present in most cases (being depression, anxiety and cognitive
impairment the most frequent ones). In one case we found deposits of iron in the basal
ganglia in the MRI, and in another case we found diffuse cortical hypometabolism with
predominantly frontal bilateral involvement and bilateral focal deficit of both caudate
and thalamus in the FDG-PET.
Conclusion
The clinical and neuroimaging findings of some cases with IA in this series are compatible
with the clinical picture of HD but also with several other alternative diagnoses.
Therefore we can not establish association between IA and HD. Larger series with more
comprehensive diagnostic workout and neuropathological studies are needed to confirm
or rule out whether IAs in the HTT gene may cause HD.
Keywords
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Article info
Publication history
Published online: April 15, 2021
Accepted:
April 12,
2021
Received in revised form:
March 27,
2021
Received:
March 3,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
