Severe infantile dentatorubral pallidoluysian atrophy with extreme expansion of CAG repeats

Abstract

References1. Leigh RJ, Robinson DA, Zee DS. A hypothetical explanation for periodic alternating nystagmus: instability in the optokinetic-vestibular system. Ann NY Acad Sci 1981;374:619 -635. 2. Baloh RW, Honrubia V, Konrad HR. Periodic alternating nystagmus. Brain 1976;99:11-26. 3. Davis DG, Smith JL. Periodic alternating nystagmus: a report of eight cases. Am J Ophthalmol 1971;72:757-762. 4. Keane JR. Periodic alternating nystagmus with downward beating nystagmus: a clinicoanatomical case study of multiple sclerosis. Arch Neurol 1974;30:399 -402. 5. Dow ER, Anastasio TJ. Induction of periodic alternating nystagmus in intact goldfish by sinusoidal rotation. Neuroreport 1997;8:2755-2759. 6. Wearne S, Raphan T, Cohen B. Control of spatial orientation of the angular vestibuloocular reflex by the nodulus and uvula.Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant disease that has a wide variety of clinical symptoms. 1 There is a correlation between age at onset and clinical symptoms. Progressive myoclonus epilepsy (PME) is a usual feature of juvenile DRPLA; but late adult DRPLA patients usually experience cerebellar ataxia and hyperkinetic involuntary movements such as choreoathetosis, often without myoclonus or epilepsy. 2 We report two unrelated patients with infantile DRPLA. Patient 1. The patient is a 4-year-old boy and the second child of healthy, nonconsanguineous Japanese parents without a family history of neurologic diseases. His father is 39 years old and his mother is 35 years old. He has a healthy 8-year-old brother. There were no major problems in the neonatal periods. He developed normally until age 6 months when his mother noticed decreased activity. At age 1 year, he could stand with support; but he began to regress slowly and became irritable. At age 2 years, he had difficulty controlling his head and swallowing, sometimes showing dystonic posture. Choreoathetosis of the limbs appeared and became prominent. At age 2 years 7 months, he had tonic convulsions. Various antiepileptic drugs did not control the convulsions.He was no longer able to fix or follow, but had light perception and normal optic fundus. Nystagmus was not noted. Muscle tone was variable, and deep tendon reflexes were exaggerated. Plantar response was absent. Oral dyskinesia, severe choreoathetosis, and dystonia were continuously seen. Myoclonus was not present.Laboratory examination including lysosomal enzyme activities, organic and amino acid analysis, and the level of lactate and pyruvate, were unremarkable. Histologic examination of the biopsied skin and muscle revealed no abnormalities.MRI of the brain showed atrophy of the cerebrum and cerebellum, brain stem, and delayed myelination ( figure, A and B).Patient 2. The patient is a 2-year-old girl and the second child of healthy, nonconsanguineous Japanese parents. Her father is 46 years old and her mother is 37 years old. Her 10-year-old brother has epilepsy and mild mental retardation. Her birth and development up to age 4 months were normal, but she could no...

Juvenile Huntington’s Disease and Other PolyQ diseases, Update on Neurodevelopmental Character and Comparative Bioinformatic Review of Transcriptomic Data

“…Patients with juvenile-onset DRPLA often have progressive myoclonic epilepsy as one of the first symptoms (Tomoda et al, 1991) and the onset in first years of life with CAG repeats between 70 and 80 (Veneziano and Frontali, 1993; Hasegawa et al, 2010). Disease onset could occur as early as six months of age (with an extreme number of CAG repeats of 90 and 93), when hyperkinetic and involuntary movements, the difficulty of controlling head movements, and seizures developed (Shimojo et al, 2001).…”

“…Atrophy of the brainstem and spinal cord was noticed as mild (Takeda and Takahashi 1996). MRI data of children with DRPLA also showed severe atrophy of the cerebrum and cerebellum, delayed myelination, and thin corpus callosum (Shimojo et al 2001). In general, juvenile-onset can be characterized by more marked pallidoluysian degeneration than dentatorubral degeneration, which is opposite to late-adult onset degeneration pattern (Yamada, 2010).…”

Integrating science to find cures in child neurology

“…1 After the 1990s, genetic diagnoses became possible for some neurological disorders. 2 From 2010, next-generation sequencing developed and became widely used in daily medical practice. 3 Consequently, genetic diagnoses improved remarkably.…”

“…In the same period, magnetic resonance imaging became available, facilitating image‐informed diagnoses for central nervous system disorders . After the 1990s, genetic diagnoses became possible for some neurological disorders . From 2010, next‐generation sequencing developed and became widely used in daily medical practice .…”

理を知り病を癒す

“…私が医師になった1980年代前半、診断に当たっては病歴を聴取し、一般身体診察および神経学的診察を行い、血液や脳脊髄液検査、脳波や神経伝導検査などの電気生理学的検査、そしてCTスキャンなどを実施した。小児神経疾患患者の多くで正確に診断することは困難だった。1980 年代後半、トレーニングの必要性を強く感じて私は国立精神・神経センターで小児神経学の修業を開始した。そこで初めて系統的な神経学的診察法を授かった。まったく同じ時期にMRIが導入され多くの中枢神経疾患の画像診断に大きな力を与えてくれた 1 ) 。1990 年代以降、特定の神経疾患では遺伝子診断が可能となった 2 ) 。2010 年代には次世代シークエンサーが開発され日常診療においても広く使われるようになった 3 ) 。その結果、遺伝子診断が急速に進歩した。…”