Machado-Joseph disease op azorean ancestry in Brazil: the Catarina kindred neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the «Catarina» kindred

Abstract

At the moment 9 seemingly independent families with the clinical diagnosis of MJD are known in Brazil. The largest family tree of Azorean ancestry contains 622 individuals in 9 generations. 236 were examined, 39 found to be affected by two examiners. Phenotypes I, II and III were expressed by 12, 23 and 4 patients with age of onset by phenotypes being 10-48, 14-54 and 30-55 respectively. Although clinically more severe, juvenile onset type I disease did not show as severe a ponto-mesencephalic atrophy on MRI as the father with type II disease of similar symptomatic duration. None of the 8 patients examined with MRI showed olivary atrophy or pallidal abnormalities. 12 affected and 23 at risk were evaluated with neuropsychological tests. Attention was normal in both groups. Verbal memory scores were below normal in the affected and there was greater decay with time than in the risk group. Both scored below normal in identifying silluettes and constructional praxis. Visual memory scores were well below normal for both, with many rotations but no omissions or confabulations. A peculiar pattern of multiplying internal details called "the fly-eye effect" was observed in 6 affected and 8 at risk. Defective color distinction when multiple colors presented close to each other, in face of proper naming of individual colors ("color simulatanagnosia"), was looked for in 29 people. 4/10 affected and 4/19 at risk showed this phenomenon. Cognitive dysfunctions in this MJD family are prominent in the sphere of vision. Whether they constitute an early manifestation in those at risk and thus serve as a clinical identifier of the illness is yet to be established. Depression was looked for in the history of the family with DSM III-R criteria and an attempt at quantification with the Montgomery-Asberg Rating Scale. There was no significant quantitative difference between affected and at risk. Once undeniably symptomatic however, the patients had no, or less depression than themselves before or at the early stages of the illness. Covert depression was appropriately excluded. Fully established MJD in this family seemed to exert a protective effect from depression.

Cognitive deficits in Machado‐Josephs disease

“…Our findings differ in several ways from the results of the only other neuropsychological study that has been performed to date in patients with MJD [17]. We could find no deficits in visual memory, and the MJD patients had no difficulty in discriminating colors when they were presented in complex visual search or memory patterns.…”

Itajaí, Santa Catarina – Azorean ancestry and spinocerebellar ataxia type 3

“…In 1988, Radvany et al studied the first two Brazilian families with a clinical diagnosis of SCA3/MJD, and in 1993, the same authors published a study on the condition in a large family of Azorean descent in the city of Itajaí, in Santa Catarina, that came to be known as the "Catarina kindred" 5,9 . At the time, this family was considered one of the largest families in the world with SCA3/MJD, and the family tree consisted of 622 individuals distributed over nine generations …”

Depressive Symptoms in Machado-Joseph Disease (SCA3) Patients and Their Relatives

“…These studies have demonstrated slow processing of visual information [27] and visual memory impairment [28], both possibly related to compromised executive and emotional functions [29]. Cognitive impairment and dementia have already been associated with SCAs in general [30] and MJD in particular [31], but more rarely with the latter.…”