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Cited by 238Connective tissue disorders researchMusculoskeletal pain and rehabilitationSpinal Dysraphism and Malformations

Neurological and spinal manifestations of the Ehlers–Danlos syndromes

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Henderson, Fraser C., Austin, Claudiu, Benzel, Edward, Bolognese, Paolo, Ellenbogen, Richard, Francomano, Clair A., Ireton, Candace, Klinge, Petra +5 more·2017·American Journal of Medical Genetics Part C: Seminars in Medical Genetics
DOI 10.1002/ajmg.c.31549
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Abstract

The Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression. This report also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto‐occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS. © 2017 Wiley Periodicals, Inc.

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  • People with hypermobile EDS are at higher risk of many comorbid problems, including gastrointestinal motility disorders, scoliosis, varicose veins, Chiari malformation, craniocervical instability and painful joint dislocation.

    “individuals with hEDS have a higher risk of a wide variety of co-morbid problems, including gastrointestinal motility disorders, scoliosis, varicose veins, Chiari malformation, craniocervical instability, painful joint dislocation, and others (Castori, 2012a; Zarate et al., 2010; Milhorat et al., 2007; Henderson et al., 2017).”

    From Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome (2018) · cites this paper as Henderson et al., 2017

  • Intubation may be difficult in hypermobile EDS because of temporomandibular joint laxity, spinal ligamentous laxity and early intervertebral disc degeneration.

    “Intubation can be problematic for hEDS patients due to temporomandibular joint laxity or spinal ligamentous laxity and early intervertebral disc degeneration (Henderson et al., 2017).”

    From Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome (2018) · cites this paper as Henderson et al., 2017

  • The study found a rate of Chiari malformations of 10% and migraines of 67%.

    “Our significant rate of Chiari malformations (10%) and migraines (67%) are also reported as common comorbidities in the literature on EDS. 33 , 34 , 35”

    From Comorbidity, misdiagnoses, and the diagnostic odyssey in patients with hypermobile Ehlers-Danlos syndrome (2023) · cites this paper as [34]

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Research works printed but not linked: 2

  1. Henderson FC, Wilson WA, Benzel EC. 2010a. Pathophysiology of cervical myelopathy: Biomechanics and deformative stress. In: Benzel EC, editor. Spine surgery: Techni- ques, complication avoidance, and manage- ment, Vol 1. 3rd edition. Philadelphia, PA: Elsevier Churchill Livingstone.
  2. Klinge PM. Histopathological evidence of clinically relevant filum pathology in Tethered Cord Syndromes with little radiographic evidence including hypermobility syndromes. CSF Research Colloquium Conference Proceed- ings, September 26, 2015, New Orleans, Louisiana.

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Authors
Henderson, F. C., Austin, C., Benzel, E., Bolognese, P., Ellenbogen, R., Francomano, C. A., Ireton, C., Klinge, P., Koby, M., Long, D., Patel, S., Singman, E. L., & Voermans, N. C.
Affiliations
  • Greater Baltimore Medical Center (US)
  • Johns Hopkins University (US)
  • Doctors Community Hospital (US)
  • North Shore University Hospital (US)
Corresponding author
Henderson, Fraser C.
ORCID
Venue
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Publisher
Wiley
Published
2017-02-21
Volume
175
Issue
1
Pages
195-211
ISSN
  • 1552-4868 (ISSN-L)
  • 1552-4876
DOI
10.1002/ajmg.c.31549
OpenAlex
W2590724600
Cited by
238
References
124
Citations by year
2026: 23 · 2025: 19 · 2024: 40 · 2023: 35 · 2022: 31 · 2021: 28 · 2020: 24 · 2019: 16 · 2018: 16 · 2017: 5 · 2013: 1
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Medical Genetics Part C Seminars in Medical Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Spinal Dysraphism and Malformations
Keywords
Ehlers-Danlos syndrome, connective tissue diseases, neurological symptoms, craniocervical instability, atlanto-occipital joint, atlantoaxial instability, intervertebral disc degeneration, peripheral nerve entrapment, migraine, idiopathic intracranial hypertension, Tarlov cyst, tethered cord syndrome, dystonia, Chiari I malformation, myelopathy, ligamentous laxity, neuromuscular disorders, diagnosis and treatment guidelines
MeSH terms
Ehlers-Danlos Syndrome, Humans, Nervous System Diseases, Spinal Diseases, Comorbidity, Practice Guidelines as Topic, Musculoskeletal Pain

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