Teaching Neuro Images : Leukodystrophy and progressive myoclonic epilepsy disclosing DRPLA

Abstract

A 25-year-old Brazilian man presented with an 8-year history of progressive myoclonic epilepsy. Familial history disclosed a Japanese paternal grandmother with late-onset parkinsonism-dementia and a paternal uncle with atypical parkinsonism. Examination showed myoclonic jerks, ataxia, and brisk tendon reflexes. Brain MRI showed diffuse leukodystrophy (figure). Genetic testing (supplemental material on the Neurology ® Web site at Neurology.org) exhibited 70/35 CAG expansions in the ATN1 gene, diagnostic of dentatorubral-pallidoluysian atrophy (DRPLA).DRPLA is a polyglutamine neurodegenerative disorder with a wide spectrum of manifestations ranging from ataxia, choreoathetosis, and dementia in adults to epilepsy and intellectual disability in children. The presence of leukodystrophy on suspicion of progressive myoclonic epilepsy should raise the possibility of DRPLA. STUDY FUNDINGNo targeted funding reported. DISCLOSUREThe authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Ethical statement: Full consent was obtained from the patient's parents and family for the case report publication.e58

Dentatorubro-Pallidoluysian Atrophy (DRPLA) among 700 Families with Ataxia in Brazil

“…Patient presented a late-onset form of ataxia, and her diagnosis was achieved after excluding all other forms of SCAs due to expanded nucleotide repeats. The only single Brazilian case previously diagnosed was a man of Japanese ancestry that presented progressive myoclonic epilepsy starting at 17 years of age [4]. Other large case series of SCAs from Brazil did not detect DRPLA [9][10][11].…”

“…DRPLA is very rare in Latin America. For instance, frequency of DRPLA was estimated to be 3.1% among SCAs in Venezuela [3], while only one single case has been described so far in Brazil in an individual of Japanese ancestry [4].…”

Dentatorubral-Pallidoluysian Atrophy: An Update

“… 3 Family history can identify neurological presentations with overlapping clinical features, such as atypical Parkinsonism with cerebellar ataxia, Parkinsonism dementia, and cerebellar atrophy. 10 , 57 …”

Dentatorubral-pallidoluysian Atrophy: An Update

“…31 DRPLA, in common with other microsatellite repeat disorders, shows genetic anticipation whereby disease symptoms occur earlier and more severely generation on generation. Previous studies have provided estimates of CAG repeat length (median and range) dependent on age at onset of symptoms: ,21 years (68 repeats; range 63-79), 21-40 years (64 repeats; range 61-69), .40 years (63 repeats; range [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. This phenomenon is thought to be driven by CAG repeat expansion in the gametes, particularly in spermatogenesis, as anticipation is more pronounced on paternal inheritance.…”

“…3 Family history can identify neurological presentations with overlapping clinical features, such as atypical Parkinsonism with cerebellar ataxia, Parkinsonism dementia, and cerebellar atrophy. 10,57 Diagnosis may be most difficult in an late-onset adult DRPLA where other differential diagnoses are more common, and the clinical presentation may be less typical; 14 when isolated ataxia is the sole clinical finding, more common causes of ataxia are likely to be considered (e.g. a background of alcohol excess), potentially resulting in DRPLA not being considered during the diagnostic work-up.…”