Importance of CAG repeat length in childhood-onset dentatorubral–pallidoluysian atrophy

Abstract

To elucidate a relationship between CAG repeat expansion length and disease progression history in patients with childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA). We retrospectively evaluated information from nine Japanese patients with disease onset reported as between 6 months and 12 years of age. CAG repeat length in these patients ranged from 62 to 93. A strong correlation was confirmed for the age of disease onset, with the onset of epilepsy and involuntary movements, emergence of regression, and autonomic symptoms. The age at becoming wheelchair-bound and initiation of tube feeding also showed a significant correlation with CAG repeat length. This is the first report detailing this aspect of DRPLA focusing on the childhood-onset population. Earlier disease milestones were revealed compared to the expected age based upon a previous report that contained data from the entire patient population, including adult-onset cases (Hasegawa et al. in Mov Disord 25:1694-1700, 2010). These results provide a basis for predicting the outcome of patients in this particular age group, as well as for assessing the results of future clinical therapeutic trials.

Neonatal SCA2 Presenting With Choreic Movements and Dystonia With Dystonic Jerks, Retinitis, Seizures, and Hypotonia

“…4,6 We must bear in mind that the following SCAs may have symptoms onset at neonatal period or during the first year of life: SCA7, SCA8, SCA13, SCA27, SCA29, and DRPLA. 9,10 In conclusion, this report expands the phenotype of veryearly-onset SCA2 (neonatal form) resembling a global encephalopathy, with hypotonia, choreic movements, dystonia with dystonic jerks, seizures, and retinitis. Family history of autosomal-dominant ataxia and marked cerebellar atrophy were crucial to guide the genetic test.…”

“…described a 4‐month‐old girl with SCA2 who presented with spontaneous dyskinetic movements . Additionally, choreoathetosis may be rarely observed in neonatal dentatorubral‐pallidoluysian atrophy (DRPLA) …”

“…The few reports of SCA2 with seizures were patients with early symptoms onset . We must bear in mind that the following SCAs may have symptoms onset at neonatal period or during the first year of life: SCA7, SCA8, SCA13, SCA27, SCA29, and DRPLA …”

“…5 Additionally, choreoathetosis may be rarely observed in neonatal dentatorubral-pallidoluysian atrophy (DRPLA). 9 The ocular involvement observed in SCA2 is typically characterized by severe impairment of fast eye-movement component, and saccadic system is much more compromised. Retinal involvement is classically found in SCA7 patients, but not in SCA2.…”

Repeat expansion diseases

“…Likewise, another CAG/polyglutamine disorder, dentatorubral-pallidoluysian atrophy (DRPLA), can manifest early in life with dystonia, epilepsy and cognitive impairment or later with chorea and ataxia, again primarily reflecting differences in the size of the expansion. Originally described in Japan, the DRPLA mutation was soon also discovered to be the cause of Haw-River syndrome in the United States, which had been thought to be a distinct disorder because it is characterized by seizures, brain calcifications and ataxia (18,75,90). In DM1, the shortest pathogenic repeats can manifest simply with cataracts and late-life myotonia whereas the longest repeats cause congenital myotonic dystrophy with profound weakness and cognitive impairment.…”