Neurologic complications of Down syndrome: a systematic review

J Neurol. 2021 Dec;268(12):4495-4509. doi: 10.1007/s00415-020-10179-w. Epub 2020 Sep 12.


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: Cerebrovascular; Down syndrome; Epilepsy; Hypotonia; Neurologic disorders; Trisomy 21.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease*
  • Autism Spectrum Disorder*
  • Comorbidity
  • Down Syndrome* / complications
  • Down Syndrome* / epidemiology
  • Humans
  • Retrospective Studies