Case series of 3 individuals of African descent with dentatorubral-Pallidoluysian atrophy

Abstract

To analyze the genetic history and clinical presentation of three individuals of African descent with Dentatorubral-Pallidoluysian Atrophy (DRPLA). DRPLA is a rare, autosomal dominantly-inherited CAG repeat disorder of the ATN1 gene characterized by myoclonus, epilepsy, ataxia, and dementia. DRPLA is most commonly seen in populations of Japanese ancestry. An African-American family with “Haw River Syndrome” was studied in North Carolina, but was later determined that Haw River Syndrome and DRPLA are the same disorder. Retrospective analysis of three cases of DRPLA affecting a father, son, and daughter of African descent; 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). Father became clinically manifest at age 38 with executive dysfunction, then progressive ataxia. 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. Daughter exhibited developmental delays in early childhood and started to have generalized seizures at age 11. She has less refractory epilepsy which has been controlled with anti-epileptic medications, vagal nerve stimulation, and CBD oil. 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.