Monozygotic Twins Suffering from Huntington’s Disease Show Different Cognitive and Behavioural Symptoms

Abstract

Monozygotic male twins, carrying the same number of trinucleotide repeats in the IT 15 Huntington disease (HD) gene, showed a different clinical course. Patient 1 presented with anxiety and chorea at the age of 40. Patient 2 showed persecution paranoia and motor impersistence at the age of 42. Both patients were monitored for 30 months using currently recommended motor and behaviour scales. No differences were observed in motor scoring besides small interevaluation fluctuations. However, on the cognitive and behaviour scales, patient 1 showed a significant worsening when compared with patient 2. Our cases support the belief that the motor symptoms and signs in HD are highly dependent on the trinucleotide expansion. However, the differences in the evolution of mental status in our patients suggest that other still unknown environmental factors are important in the phenotypic expression of Huntington’s disease.

The Neuropathology of Huntington’s Disease

“…Still others experience marked motor, mood, and cognitive symptoms simultaneously (Brandt and Butters 1986;Folstein 1989;Myers et al 1991;Claes et al 1995;Zappacosta et al 1996; Thompson et al 2002). Interestingly, observations in monozygotic twins who inherited identical HTT genes with the same repeat length exhibit marked differences in their symptom profile (Georgiou et al 1999;Friedman et al 2005;Gomez-Esteban et al 2007). The onset of clinical symptoms in individual HD cases is generally correlated with the number of CAG repeats (Wexler et al 2004), as does the disease severity, but there is no consistent relationship between CAG repeat length and symptom subtype (MacMillan et al 1993;Telenius et al 1994;Claes et al 1995;Zappacosta et al 1996).…”

“…As discussed later, the cell loss in the cerebral cortex also shows a high degree of variability. Most interestingly, this variable pattern of pathology appears to reflect the highly variable symptomatology of cases with HD even among cases possessing the same number of CAG repeats (Georgiou et al 1999;Friedman et al 2005;Gomez-Esteban et al 2007;Tippett et al 2007;Thu et al 2010). …”

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.…”

Restless Legs Syndrom bei Monozygoten und Dizygoten Zwillingen

“…Bird & Omenn 1975;Sudarsky et al 1983;Anca et al 2004;Friedman et al 2005;Gomez-Esteban et al 2007). Fallberichte MZ Zwillingspaare zeigten trotz identischer Anzahl von CAG-Triplett-Repeats eine unterschiedliche Symptomatik und/oder einen abweichenden Verlauf der Erkrankung (Georgiou et al 1999;Anca et al 2004;Friedman et al 2005;Gomez-Esteban et al 2007 (Rothdach et al 2000;Phillips et al 2000;Berger et al 2004;Hogl et al 2005).…”