Neurological and spinal manifestations of the Ehlers–Danlos syndromes

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Vol. 175; no. 1; pp. 195 - 211
• Main Authors: Henderson, Fraser C., Austin, Claudiu, Benzel, Edward, Bolognese, Paolo, Ellenbogen, Richard, Francomano, Clair A., Ireton, Candace, Klinge, Petra, Koby, Myles, Long, Donlin, Patel, Sunil, Singman, Eric L., Voermans, Nicol C.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2017
• Subjects: atlantoaxial instability; Brain; Central nervous system diseases; Comorbidity; Congenital defects; Connective tissues; craniocervical instability; Cysts; Deformation; Degeneration; Disease control; Disorders; Dystonia; Ehlers-Danlos syndrome; Ehlers-Danlos Syndrome - complications; Ehlers-Danlos Syndrome - pathology; Ehlers-Danlos Syndrome - physiopathology; Entrapment; Epidemiology; Fragility; Gene expression; Genetics; Headache; Humans; Hypertension; Intervertebral discs; Kyphosis; Ligaments; Migraine; Motor task performance; Musculoskeletal Pain - etiology; Myalgia; Nervous system; Nervous System Diseases - diagnosis; Nervous System Diseases - pathology; Neural tube defects; Neurological diseases; Pain; Perineurium; Peripheral nerves; Practice Guidelines as Topic; Skin; Spinal cord; Spinal Diseases - diagnosis; Spinal Diseases - pathology; Spine; Spine (cervical); Stability; tethered cord syndrome; Vibration; Walking; craniocervical instability; Ehlers-Danlos syndrome; headache; atlantoaxial instability; tethered cord syndrome
• ISSN: 1552-4868; 1552-4876
• DOI: 10.1002/ajmg.c.31549

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.