Monozygotic Twins Discordant for Huntington Disease After 7 Years

Abstract

Background: Huntington disease (HD) has only rarely been identified in identical twins. All described twins have had disease onset within 1 year of each other, suggesting that disease onset is determined solely by genetic influences.Objective: To describe a unique set of monozygotic twins in whom clinical HD onset is at least 7 years apart.Design: A 71-year-old woman was diagnosed as having HD based on medical history, physical examination results consistent with HD, and a CAG trinucleotide repeat number of 39 in the HD gene on chromosome 4. Her onset was 6 years earlier. Her genetically confirmed identical twin, carrying the same number of CAG repeats, was neurologically healthy when examined the next year. Only

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

“…The affected MZ male twin had the full mutation, whereas the unaffected twin was mosaic for the full mutation and the premutation. Another example is a pair of MZ twins who had the same 39 expansion of the CAG repeat in the HD gene, were discordant for clinical onset of Huntington disease by 7 years [Friedman et al, 2005].…”

Cortical interneuron loss and symptom heterogeneity in Huntington disease

“…1,2 The disease is caused by an unstable expansion of CAG repeats in the HTT gene. 3 Although the correlation between CAG repeat size and onset age is significant, it is widely acknowledged that the repeat size is a poor indicator of symptom variability.…”

First use of creatine hydrochloride in premanifest Huntington disease

“…This has been amply illustrated by variation in disease manifestation and onset in monozygotic twins (either reared together or apart) [57][58][59][60][61] and most notably in the Venezuelen kindred 3 . Whilst this adds further complexity to understanding the disease process, it presents an exciting opportunity to impact on the disease course via non-pharmacological means, and without the need to directly modify gene function, which has proved enigmatic to-date.…”