Objective: To analyze the demographics, genetic history, co-morbidities, and clinical presentation of three individuals of African descent with Dentatorubral-Pallidoluysian Atrophy (DRPLA).

Background: DRPLA is a rare, autosomal dominantly-inherited disorder of the ATN1 gene characterized by myoclonus, epilepsy, ataxia, and dementia. The number of CAG repeats increases generationally when the ATN1 gene is paternally inherited. Larger repeat expansions are usually associated with earlier clinical manifestation. DRPLA is most commonly seen in populations of Japanese ancestry with significantly lower rates in non-Asian populations. An African-American family with “Haw River Syndrome” was studied in North Carolina, but it was later determined that Haw River Syndrome and DRPLA are the same disorder.

Method: Retrospective analysis of three cases of DRPLA affecting a father, son, and daughter of African descent. Comprehensive review of medical records was completed in a 50 year-old male from Sierra Leone with 61 CAG repeats in allele 1 of ATN1 gene and his 2 offspring, a son (71 repeats) and daughter (69 repeats).

Results: Father became clinically manifest at age 38 with executive dysfunction, then progressive ataxia, and later a generalized seizure. Son showed signs of developmental delay at age 4 and later developed refractory, generalized epilepsy at age 7. He was treated with multiple anti-epileptic medications and vagal nerve stimulation as well as deep-brain stimulation for severe dystonia. He passed away at age 16. Daughter exhibited developmental delays in early childhood and started to have generalized seizures at age 11. She has less refractory epilepsy which has been somewhat controlled with anti-epileptic medications, vagal nerve stimulation, and CBD oil.

Conclusion: DRPLA is not commonly seen in individuals of African descent. In these three cases, the clinical presentation differed among the offspring who predominantly experienced seizures, dystonia, and intellectual disability, whereas, the father presented predominantly with ataxia and cognitive dysfunction.

References: Adachi N, Arima K, Asada T, Kato M, Minami N, Goto Yi, Onuma T, Ikeuchi T, Tsuji S, Hayashi M, Fukutani Y. Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):258-60. Citation on PubMed Hayashi Y, Kakita A, Yamada M, Koide R, Igarashi S, Takano H, Ikeuchi T, Wakabayashi K, Egawa S, Tsuji S, Takahashi H. Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain. Acta Neuropathol. 1998 Dec;96(6):547-52. Citation on PubMed Ikeuchi T, Koide R, Onodera O, Tanaka H, Oyake M, Takano H, Tsuji S. Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA. Clin Neurosci. 1995;3(1):23-7. Citation on PubMed Ikeuchi T, Onodera O, Oyake M, Koide R, Tanaka H, Tsuji S. Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Semin Cell Biol. 1995 Feb;6(1):37-44. Review. Citation on PubMed Katsuno M, Banno H, Suzuki K, Takeuchi Y, Kawashima M, Tanaka F, Adachi H, Sobue G. Molecular genetics and biomarkers of polyglutamine diseases. Curr Mol Med. 2008 May;8(3):221-34. Review. Citation on PubMed Koide R, Onodera O, Ikeuchi T, Kondo R, Tanaka H, Tokiguchi S, Tomoda A, Miike T, Isa F, Beppu H, Shimizu N, Watanabe Y, Horikawa Y, Shimohata T, Hirota K, Ishikawa A, Tsuji S. Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings. Neurology. 1997 Dec;49(6):1605-12. Citation on PubMed Licht DJ, Lynch DR. Juvenile dentatorubral-pallidoluysian atrophy: new clinical features. Pediatr Neurol. 2002 Jan;26(1):51-4. Citation on PubMed Tsuji S. Dentatorubral-pallidoluysian atrophy: clinical aspects and molecular genetics. Adv Neurol. 2002;89:231-9. Review. Citation on PubMed Veneziano L, Frontali M. DRPLA. 1999 Aug 6 [updated 2016 Jun 9]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from http://www.ncbi.nlm.nih.gov/books/NBK1491/ Citation on PubMed Yamada M, Wood JD, Shimohata T, Hayashi S, Tsuji S, Ross CA, Takahashi H. Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral-pallidoluysian atrophy. Ann Neurol. 2001 Jan;49(1):14-23. Citation on PubMed

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MDS Abstracts - https://www.mdsabstracts.org/abstract/case-series-of-3-individuals-of-african-descent-with-dentatorubral-pallidoluysian-atrophy/