A família Drew de Walworth: um século após a avaliação inicial finalmente o diagnóstico doença de Machado-Joseph

Abstract

RESUMO -As enfermidades heredo-degenerativas, entre elas as ataxias cerebelares autossômicas dominantes, agora conhecidas como ataxias espinocerebelares (AEC), correspondem a extenso grupo de doenças com grande heterogeneidade genética. Algumas formas de AEC, em especial a doença de Machado-Joseph (DMJ), caracteriza-se por acentuada variabilidade de expressão fenotípica intra e inter-familial. Em 1895, na Grã-Bretanha, foi descrita uma família com uma forma autossômica dominante de AEC que viria a ser conhecida como a família Drew de Walworth. Desde sua descrição inicial até 1995, quando do diagnóstico genético final de DMJ, vários membros e gerações desta família foram examinados e seus achados descritos na literatura por famosos neurologistas como Gowers, Stewart, Collier, Kinnier-Wilson, Turner, Worster-Drought, Ferguson, Critchley e Anita Harding. Neste artigo, os autores descrevem a trajetória histórica tortuosa e as discussões sobre os diagnósticos nosológicos propostos no decorrer de um século, com o propósito de mostrar a impressionante e atraente complexidade que envolve este grupo de doenças neurodegenerativas.

Spinocerebellar ataxias: microsatellite and allele frequency in unaffected and affected individuals

“…In the patient group in the present study, SCA3 locus had more expanded alleles than other loci. This corroborates the hypothesis that the Portuguese and African populations brought a pool of founding genes to Brazil with a common mutation in the SCA3 gene identified as the cause of MJD (SCA3) 37,[41][42][43] . However, other studies of the Portuguese population did not show any correlation between the frequency of the large normal alleles and the frequency of the disease [20][21][22][23] .…”

“…Alleles with a number of (CAG)n greater than 27 are observed in the Portuguese, American, Japanese and African populations, of which there is a high incidence in SCA3 patients 13,37,41 . In the patient group in the present study, SCA3 locus had more expanded alleles than other loci.…”

Reconstructing the History of Machado-Joseph Disease

“…In 1895, William Gowers (1845-1915; National Hospital for the Paralysed and Epileptics, Queen Square, London, UK) examined a patient named William Drew, and his final diagnostic was paralysis agitans, in the National Hospital (now the National Hospital for Neurology and Neurosurgery). Since then and until recently, many clinician-researchers have examined members of the Drew family of Walworth [20]. With a clear autosomal dominant pattern of inheritance (for details, see Kang et al [18]) and pleomorphic clinical characteristics among patients (euphoria, emotional instability, and without cognitive impairment; vertical ophthalmoparesis, nystagmus, and lid retraction; pyramidal signs; sensitive disturbances; extrapyramidal manifestations -including parkinsonism; dysarthria; altered control of sphincters; and cerebellar ataxia) [21], the members of the family were examined through decades by others including T. Grainger Stewart, James Collier, Kinnier-Wilson, Aldren Turner, Worster-Drought, Fergunson and Critchley (1929), J.…”

“…With a clear autosomal dominant pattern of inheritance (for details, see Kang et al [18]) and pleomorphic clinical characteristics among patients (euphoria, emotional instability, and without cognitive impairment; vertical ophthalmoparesis, nystagmus, and lid retraction; pyramidal signs; sensitive disturbances; extrapyramidal manifestations -including parkinsonism; dysarthria; altered control of sphincters; and cerebellar ataxia) [21], the members of the family were examined through decades by others including T. Grainger Stewart, James Collier, Kinnier-Wilson, Aldren Turner, Worster-Drought, Fergunson and Critchley (1929), J. Brown (1975), Anita Harding (1982 and1984) and Giunti, and Sweeney and Harding (1995) [20]. In 1995, Giunti, Sweeney, and Harding published a study presenting the diagnosis of MJD for the family [20,22].…”

“…Brown (1975), Anita Harding (1982 and1984) and Giunti, and Sweeney and Harding (1995) [20]. In 1995, Giunti, Sweeney, and Harding published a study presenting the diagnosis of MJD for the family [20,22].…”