Presentation Modes, Anticipation, and Penetrance: A Case Series of Huntington’s Disease

TL;DR

This paper presents three Huntington’s disease cases, highlighting how the disease presents, its genetic anticipation, and variable penetrance.

Contribution

The study contributes a case series illustrating presentation modes, anticipation, and penetrance in Huntington’s disease.

Findings

HD typically presents with psychiatric, cognitive, and motor symptoms.

Anticipation leads to earlier onset in successive generations due to CAG repeat expansion instability.

Reduced penetrance alleles are common, with disease threshold at 35 CAG repeats.

Abstract

Huntington’s disease (HD) is an inherited, potentially incurable neurodegenerative disease. It typically presents as a triad of progressive psychiatric, cognitive, and motor symptoms and shows significant anticipation and penetrance. It is caused by trinucleotide CAG (cytosine, adenine, guanine) repeat expansion in the Huntington (HTT) gene. It exhibits significant anticipation, earlier onset in successive generations within a pedigree, which is caused by the instability of the HTT gene, along with a further increase in its length in subsequent generations. Reduced penetrance alleles of HD are relatively common in the general population. The threshold for disease is 35, with complete penetrance above 39 and incomplete penetrance for 36, 37, and 38 repeats. A series of three cases of HD have been discussed here, along with their pattern of presentation, anticipation, and genetic variation.

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