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Neurologic complications of Down syndrome: a systematic review

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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.

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Authors and Affiliations

  1. Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA

    Jonathan D. Santoro, Dania Pagarkar & Michael S. Rafii

  2. Division of Neurology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Kelli C. Paulsen

  3. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Jonathan D. Santoro, Kelli C. Paulsen & Michael S. Rafii

  4. Faculty of Medicine, Queen’s University, Kingston, ON, Canada

    Duong T. Chu

  5. Department of Neurology, Medical University of South Carolina, Charleston, SC, USA

    Mattia Rosso

  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

    Pat Levitt

  7. Alzheimer’s Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Michael S. Rafii

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Appendix A

Appendix A

Entry terms

Syndrome, Down.

Mongolism.

47,XY, + 21.

Trisomy G.

47,XX, + 21.

Down's Syndrome.

Downs Syndrome.

Syndrome, Down's.

Trisomy 21.

Trisomy 21, Mitotic Nondisjunction.

Down Syndrome, Partial Trisomy 21.

Partial Trisomy 21 Down Syndrome.

Trisomy 21, Meiotic Nondisjunction.

Search terms and phrases

Hypotonia

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Intellectual disability

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Filters used: Review, Systematic Review, Randomized Control Trial.

Hearing and visual impairment

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Search Phrase Using MeSH Terms: (“Hearing Loss”[Mesh]) AND “Down Syndrome”[Mesh].

Cervical instability

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Autism

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Epilepsy, infantile spams

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Epilepsy, Lennox-Gastaut

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Because MeSH terms produced limited results, the search was cross-checked using the following general search phrase entered into the Pubmed search engine: “Lennox–Gastaut and down syndrome”.

Epilespy, LOMEDS

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Epilepsy, late in life

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“myoclonic epilepsy in down syndrome”.

Epilepsy, Alzheimer’s disease

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Moyamoya

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Cerebral amyloid angiopathy

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Alzheimer’s disease

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Disorders of attention

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Depression

Search Phrase Using MeSH Terms: (“Down Syndrome”[Mesh]) AND “Depression”[Mesh].

Catatonia

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Because MeSH terms produced limited results, the search was cross-checked using the following general search phrase entered into the Pubmed search engine: “down syndrome and catatonia”.

Down syndrome regression disorder

Because no MeSH terms existed for this pathology, the following general search phrase was entered into the Pubmed search engine: “down syndrome disintegrative disorder”.

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Santoro, J.D., Pagarkar, D., Chu, D.T. et al. Neurologic complications of Down syndrome: a systematic review. J Neurol 268, 4495–4509 (2021). https://doi.org/10.1007/s00415-020-10179-w

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