Machado-Joseph disease in Brazil: from the first descriptions to the emergence as the most common spinocerebellar ataxia

Abstract

Machado-Joseph disease is an autosomal dominant inherited disorder of Azorean ancestry firstly described in 1972. Since then, several Brazilian researchers have studied clinical and genetic issues related to the disease. Nowadays, Machado-Joseph disease is considered the most common spinocerebellar ataxia worldwide. Machado-Joseph disease still has no specific therapy to arrest progression, but the unclear pathophysiological mechanism, features related to genetic characteristics, phenotype variability, apparently global involvement of the nervous system in the disease and the therapeutic challenges continue to attract investigators in the field of spinocerebellar ataxias. Brazilian researchers have distinguished themselves in the ongoing investigation seeking new knowledge about Machado-Joseph disease.

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 …”

“…Clinical manifestations include cerebellar ataxia, particularly gait ataxia, bulging eyes, dysarthria, pyramidal signs, progressive ophthalmoplegia, dystonia, parkinsonism, lower motor neuron disease and peripheral neuropathy, with fasciculations and amyotrophy 1,2,3,4,5 . In Brazil, several studies have focused on the prevalence and clinical presentation of this neurodegenerative disease in different areas, particularly in the south of the country 2,3,5 .…”

“…In Brazil, several studies have focused on the prevalence and clinical presentation of this neurodegenerative disease in different areas, particularly in the south of the country 2,3,5 . Here we discuss the historical importance of the city of Itajaí, in the state of Santa Catarina, as the origin of most cases of SCA3 families in Brazil.…”

Machado-Joseph Disease in the context of the person/family that experiences it: daily changes and future expectations Doença de Machado-Joseph no contexto da pessoa/família que a vivencia: alterações cotidianas e expectativas futuras

“…9 In this context, Brazilian researchers have excelled in research in search of new knowledge about this disease. 15 However, even with the numerous investments, the MJD is still little discussed and known by society in general.…”

Diagnosis at a first glance? "Bulging eyes" as a clue for a more accurate diagnosis in spinocerebellar ataxias

“…SCA3 is the most common SCA worldwide, and this is not different in Brazil 5 . SCA represents an extensive and complex group of autosomal dominant neurodegenerative diseases, and to date, SCA1, SCA2, SCA3, SCA6 and SCA7 are the most frequently identified subtypes.…”