Neurologic complications of Down syndrome: a systematic review
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REVIEW
Neurologic complications of Down syndrome: a systematic review Jonathan D. Santoro1,3 · Dania Pagarkar1 · Duong T. Chu4 · Mattia Rosso5 · Kelli C. Paulsen2,3 · Pat Levitt6 · Michael S. Rafii1,3,7 Received: 11 August 2020 / Revised: 17 August 2020 / Accepted: 19 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Down syndrome (DS) is one of the most well-recognized genetic disorders. Persons with DS are known to have a variety of co-morbid medical problems, affecting nearly all organ systems. Improved healthcare interventions and research have allowed for increased life span of persons with DS, although disorders of the neurologic system remain underexplored. The purpose of this systematic review is to provide clinically pertinent information on the neurological phenotypes of frequently occurring or clinically relevant conditions. A retrospective review of MEDLINE, Scopus, and Pubmed were used to identify sources among seventeen, clinically relevant, search categories. MeSH terms all contained the phrase “Down Syndrome” in conjunction with the topic of interest. ‘Frequently-occurring’ was defined as prevalent in more than 10% of persons with DS across their lifespan, whereas ‘clinically-relevant’ was defined as a disease condition where early diagnosis or intervention can augment the disease course. In total, 4896 sources were identified with 159 sources meeting criteria for inclusion. Seventeen clinical conditions were grouped under the following subjects: hypotonia, intellectual and learning disability, cervical instability, autism spectrum disorder, epilepsy, cerebrovascular disease, Alzheimer’s disease and neuropsychiatric disease. The results of this review provide a blueprint for the clinical neurologist taking care of persons with DS across the age spectrum and indicate that there are many underrecognized and misdiagnosed co-occurring conditions in DS, highlighting the need for further research. Keywords Down syndrome · Trisomy 21 · Neurologic disorders · Epilepsy · Hypotonia · Cerebrovascular
Introduction * Jonathan D. Santoro [email protected] 1
Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA
2
Division of Neurology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
3
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
4
Faculty of Medicine, Queen’s University, Kingston, ON, Canada
5
Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
6
Department of Pediatrics and Program in Developmental Neuroscience and Developmental Neurogenetics, The Saban Research Institute, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
7
Alzheimer’s Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Down syndrome (DS) is one of the most common genetic disorders and the most c
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