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Ehlers–Danlos syndrome and neurological features: a review

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Abstract

Ehlers–Danlos Syndrome is a term that comprises a variety of inherited connective tissue disorders characterized primarily by skin hyperextensibility, joints hypermobility and excessive dislocations, easy bruisability, generalized fragility. If much is known about orthopedic or physiatric features of this syndrome, poor is known about the neurological ones. Thus neurological assessment is very important due to the possible various clinical manifestations in this syndrome.

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References

  1. Beighton P, De Paepe A, Hal JG et al (1992) Molecular nosology of heritable disorders of connective tissues. Am J Med Genet 42:431–448

    Article  CAS  PubMed  Google Scholar 

  2. Beighton P, De Paepe A, Danks D et al (1988) International nosology of heritable disorders of connective tissue, Berlin 1986. Am J Med Genet 29:581–594

    Article  CAS  PubMed  Google Scholar 

  3. Beighton P, de Paepe A, Steinmann B, Tsipuoras P, Wenstrup RJ (1998) Ehlers-Danlos syndrome: revised nosology. Am J Med Genet 77:31–37

    Article  CAS  PubMed  Google Scholar 

  4. Brunk I, Stover B, Ikonomidou C, Brinckmann J, Neumann L (2004) Ehlers–Danlos syndrome type VI with cystic malformations of the meninges in a 7-years-old girl. Eur J of Pediatrics 163(4–5):214–217

    Article  Google Scholar 

  5. Byers PH (1997) Ehlers-Danlos syndrome. In: Rimoin DI, Commor JM, Pyeritz RE (eds) Energy and Rimoin's principles and practice of medical genetics, 3rd edn. Churchill Livingstone, New York, pp 1067–1081

    Google Scholar 

  6. Chen BM, Grinnel AD (1995) Integrins and modulation of transmitter release from motor nerve terminals by stretch. Science 269:1578–1580

    Article  CAS  PubMed  Google Scholar 

  7. Chevassus-au-Louis N, Baraban SC, Gaiarsa JL, Ben-Ari Y (1999) Cortical malformations and epilepsy: new insight from animal models. Epilepsia 40:811–821

    Article  CAS  PubMed  Google Scholar 

  8. Cupo LN, Pyeritz RE, Olson JL (1981) Ehlers–Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphisema and cerebral heterotopias. Am J Med 71:1051–1058

    Article  CAS  PubMed  Google Scholar 

  9. Danlos EA (1908) Un cas de cutis laxa avec tumeurs pur contusion chronique des coudes et des genous. Bull Soc Franc Dermatol Syphiligr 19:70–72

    Google Scholar 

  10. De Graaf AS (1973) Neuralgic amyotrophy in identical twins with Ehlers–Danlos syndrome. Eur Neurol 9:190–196

    Article  PubMed  Google Scholar 

  11. Debrun GM, AletichVA MillerNR, DeKeiset RJW (1996) Three cases of spontaneous direct carotid cavernous fistulas associated with Ehlers–Danlos syndrome type IV. Surg Neurol 46:247–252

    Article  CAS  PubMed  Google Scholar 

  12. Desal H, Toulgoat F, Raoul S, Guillon B, Bommard S, Naudou-Giron E, Auffray-Calvier E, de Kersaint-Gilly A (2005) Ehlers–Danlos syndrome type IV and recurrent carotid-cavernous fistula. Review of the literature, endovascular approach, technique and difficulties. Neuroradiology 47:300–304

    Article  CAS  PubMed  Google Scholar 

  13. Echaniz-laguna A, de Saint-Martin A, Lafontaine AL, Tasch E, Thomas P, Hirsh E (2000) Bilateral focal polymicrogyria in Ehlers–Danlos syndrome. Arch Neurol 57:123–127

    Article  CAS  PubMed  Google Scholar 

  14. Edwards A, Taylor GW (1969) Ehlers–Danlos syndrome with vertebral artery aneurysm. Proc R Soc Med 62:734–735

    CAS  PubMed  Google Scholar 

  15. Ehlers E (1901) Danische dermatologische Gesellschaft 15. Sitzung vom 15 Dezember 1900. Dermatol Z 8:173–175

    Google Scholar 

  16. Eksioglu Y, Scheffer IE, Cardenas P (1996) Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron 16:77–87

    Article  CAS  PubMed  Google Scholar 

  17. El-Shaker M, Watts HG (1991) Acute brachial plexus neuropathy secondary to halo-gravity traction in a patient with Ehlers–Danlos syndrome. Spine 16:385–386

    Article  CAS  PubMed  Google Scholar 

  18. Ezzeddine H, Sabourand P, Eschard C, El Tourjuman O, Bednarek N, Motte J (2005) Bilateral frontal polymicrogyria and Ehlers–Danlos syndrome. Arch de Pediatrie 12:173–175

    Article  CAS  Google Scholar 

  19. Farag TI, Schimke RN (1989) Ehlers–Danlos syndrome: a new oculo-scoliotic type with associated polyneuropathy? Clin Genet 35:121–124

    Article  CAS  PubMed  Google Scholar 

  20. Fox JW, Lamperti ED, Ekşioğlu YZ, Hong SE, Feng Y, Graham DA, Scheffer IE, Dobyns WB, Hirsch BA, Radtke RA, Berkovic SF, Huttenlocher PR, Walsh CA (1998) Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia. Neuron 21:1315–1325

    Article  CAS  PubMed  Google Scholar 

  21. Franceschini P, Guala A, Licata D, Di Cara G, Franceschini D (2000) Arterial tortuosity syndrome. Am J Med Genet 91:141–143

    Article  CAS  PubMed  Google Scholar 

  22. Galan E, Koussef BG (1995) Peripheral Neuropathy in Elhers–Danlos syndrome. Pediatr Neurol 12:242–245

    Article  CAS  PubMed  Google Scholar 

  23. Gloviczki P, Oderich G, Panneton JM, Thomas C, Bower TC, Noralane M, Lindor NM, Kennet JC, Cherry J, Noel AA, Kalra M, Sullivan T (2005) The spectrum, management and clinical outcome of Ehlers–Danlos syndorme type IV: a 30-year experience. J Vasc Surg 42:98–106

    Article  PubMed  Google Scholar 

  24. Grahame R (2000) Hypermobility−not a circ act. Int J Clin Pract 54(5):314–315

    CAS  PubMed  Google Scholar 

  25. Gupta P, Gleeson AP (2000) A rare case of head injury associated with Ehlers–Danlos syndrome. Injury Int J Care Injured 31:641–643

    CAS  Google Scholar 

  26. Halbach VV, Higashida RT, Dowd CF, Barnwell SL, Hieshima GB (1990) Treatment of carotid cavernous fistulas associated with Ehlers–Danlos syndrome. Neurosurgery 26:1021–1027

    Article  CAS  PubMed  Google Scholar 

  27. Hernández A, Aguirre-Negrete MG, González-Flores S, Reynoso-Luna MC, Fragoso R, Nazará Z, Tapia-Arizmendi G, Cantú JM (1986) Ehlers–Danlos features with progeroid facies and mild mental retardation. Further delineation of the syndrome. Clin Genet 30(6):456–461

    Article  PubMed  Google Scholar 

  28. Herrero F (1995) Ehlers–Danlos syndrome and epilepsy: a case study. Epilepsia 36(3):240

    Google Scholar 

  29. Holzschuch M, Woerrgen C, Brawanski A (1996) Transcranial Doppler sonography in a patient with Ehlers–Danlos syndrome: case report. Neurosurgery 39:170–172

    Article  Google Scholar 

  30. Hunter GC, Malone JM, Moore WS, Misiarowski DL, Chvapli M (1982) Vascular manifestations in patients with Ehlers–Danlos syndrome. Arch Surg 117:495–498

    CAS  PubMed  Google Scholar 

  31. Jacome DE (1999) Epilepy in Ehlers–Danlos syndrome. Epilepsia 19:467–473

    Article  Google Scholar 

  32. Jacome DE (1999) Headache in Ehlers–Danlos syndrome. Chefalalgia 19:791–796

    CAS  Google Scholar 

  33. Jansen LH (1955) The structure of the connective tissue, an explanation of the symptoms of Ehlers–Danlos syndrome. Dermatologica 110:108–120

    Article  CAS  PubMed  Google Scholar 

  34. Johnson SAM (1949) Ehlers–Danlos syndrome: a clinical and genetic study. Arch Dermatol Syph 60:82–105

    CAS  Google Scholar 

  35. Kayed K, Kass B (1979) Acute multiple brachial neuropathy and Ehlers–Danlos syndrome. Neurology 29:1620–1621

    CAS  PubMed  Google Scholar 

  36. Kosho T, Miyake N, Hatamochi A et al (2010) A new Ehlers–Danlos syndrome with craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and multisystem fragility-related manifestations. Am J Med Genet 152A(6):1333–1346

    PubMed  Google Scholar 

  37. Krog M, Almgren B, Eriksson I, Nordstrom S (1983) Vascular complications in the Ehlers–Danlos syndrome. Acta Chir Scand 149:279–282

    CAS  PubMed  Google Scholar 

  38. Lees MH, Menashe VD, Sunderland CO (1969) Ehlers–Danlos syndrome associated with multiple pulmonary artery stenoses and tortuous systemic arteries. J Pediatr 75(6):1031–1036

    Article  CAS  PubMed  Google Scholar 

  39. Lumley MA, Jordan M, Rubinstein R, Tsipouras P, Evans MI (1994) Psychosocial functioning in the Ehelrs–Danlos syndrome. Am J Med Genet 53:149–152

    Article  CAS  PubMed  Google Scholar 

  40. Mathew T, Sinha S, Taly AB, Arunodaya GR, Srikanth SG (2005) Neurological manifestations of Ehlers–Danlos syndrome. Neurol India 53(3):339–341

    Article  CAS  PubMed  Google Scholar 

  41. McKusick VA (1956) Heritable disorders of connective tissue. Mosby, St. Louis

    Google Scholar 

  42. Mirza FH, Smith PL, Lim WN (1979) Multiple aneurysms in a patient with Ehlers–Danlos syndrome: angiography without sequelae. Am J Radiol 132:993–995

    CAS  Google Scholar 

  43. Miyake N, Kosho T, Mizumoto S et al (2010) Loss-of-function mutations of CHST14 in a new type of Ehlers–Danlos syndrome. Human Mutate 31(8):966–974. doi:10.1002/humu.21300

    Article  CAS  Google Scholar 

  44. Nagashima C, Tsuji R, Kubota M, Tajima J (1981) Atlanto-axial, atlanto-occipital dislocations, development canal stenosis in the Ehlers–Danlos syndrome. No Shinkei geka 9:601–608

    CAS  PubMed  Google Scholar 

  45. North KN, Whiteman DA, Pepin MG, Byers PH (1995) Cerebrovascular complications in Ehlers–Danlos syndrome type IV. Ann Neurol 38:960–964

    Article  CAS  PubMed  Google Scholar 

  46. Papapetropoulos T, Tsankanikas C (1981) Brachial neuropathy and Ehlers–Danlos syndrome. Neurology 31:642–643

    CAS  PubMed  Google Scholar 

  47. Pepin M, Schwarze U, Superti-Fuga A, Byers PH (2000) Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type. N Eng J Med 342:673–680

    Article  CAS  Google Scholar 

  48. Pinnel SR, Krane SM, Kenzora JE, Glincher MJ (1972) A heritable disorder of connective tissue: hydroxylisine-deficient collagen disease. N Eng J Med 286:1013–1020

    Article  Google Scholar 

  49. Pope FM (1991) Molecular analysis of Ehlers–Danlos syndrome type II. Br J Rheumatol 30:163–166

    Article  CAS  PubMed  Google Scholar 

  50. Pouassaint TY, Fox JW, Dobyns WB, Radke R, Scheffer IE, Berkovic SF, Barnes PD, Huttenlocher PR, Walsh CA (2000) Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings. Pediatr Radiol 30:748–755

    Article  Google Scholar 

  51. Pretorius ME, Butler IJ (1983) Neurologic manifestation of Ehlers–Danlos syndrome. Neurology 33:1087–1089

    CAS  PubMed  Google Scholar 

  52. Pyeritz RE (2000) Ehlers–danlos syndrome. In: Goldmann L, Bennet JC (eds) Cecil textbook of medicine, 21st edn. Saunders, Philadelphia, pp 1119–1120

    Google Scholar 

  53. Rowe PC, Bou-Holaigah I, Kan JS, Calkins H (1995) Is neurally mediated hypotension an unrecognised cause of chronic fatige? Lancet 345:623–624

    Article  CAS  PubMed  Google Scholar 

  54. Rubinstein MK, Cohen NH (1964) Ehelrs–Danlos syndrome associated with multiple intracranial aneurysms. Neurology 14:125–132

    CAS  PubMed  Google Scholar 

  55. Sacheti A, Szemere J, Bernstein B, Tafas T, Schechter N (1997) Chronic pain is a manifestation of the Ehlers–Danlos syndrome. J Pain Symptom Manage 14:88–93

    Article  CAS  PubMed  Google Scholar 

  56. Sakai LY (1995) The extracellular matrix. Sci Am 2:58–67

    CAS  Google Scholar 

  57. Savasta S, Crispino M, Valli M, Calligaro A, Zambelloni C, Poggiani C (2007) Subependymal periventricular heterotopias in a patient with Ehlers–Danlos sindrome: a new case. J Child Neurol 22:317–320

    Article  PubMed  Google Scholar 

  58. Savasta S, Valli M (2008) Ehlers–Danlos syndromes (chapter 56). In: Ruggieri M, Castroviejo IP, Di Rocco C (eds) Neurocutaneous Disorders, 1st edn. Springer Wien, New York, pp 887–906

    Chapter  Google Scholar 

  59. Schady W, Ochoa J (1984) Ehlers–Danlos syndrome in association with tomaculous neuropathy. Neurology 34:1270

    CAS  PubMed  Google Scholar 

  60. Schievink WI, Gordon OK, Tourje J (2003) Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study. Neurosurgery 54:65–71

    Google Scholar 

  61. Schievink WI, Limburg M, Oorthuys JW, Fleury P, Pope FM (1990) Cerebrovascular disease in Ehlers–Danlos syndrome type IV. Stroke 21:626–632

    CAS  PubMed  Google Scholar 

  62. Schievink WI, Piepgras DG, Earnest VE, Gordon H (1991) Spontaneous carotid-cavernous fistulae in Ehlers–Danlos syndrome type IV. J Neurosurg 74:991–998

    Article  CAS  PubMed  Google Scholar 

  63. Scholman A, Kepes JJ (1967) Bilateral spontaneous carotid-cavernous fistulae in Ehlers–Danlos syndrome. J Neurosurg 26:82–86

    Article  Google Scholar 

  64. Shapiro SK (1952) A case of Meekrin–Ehlers–Danlos syndrome with neurological manifestation. J Nerv Ment Dis 115:64–71

    Article  CAS  PubMed  Google Scholar 

  65. Sheen VL, Jansen A, Chen MH, Parrini E, Morgan T, Ravenscroft R, Ganesh V, Underwood T, Wiley J, Leventer R, Vaid RR, Ruiz DE, Hutchins GM, Menasha J, Willner J, Geng Y, Gripp KW, Nicholson L, Berry-Kravis E, Bodell A, Apse K, Guerrini R, Walsh CA (2005) Filamin A mutation cause periventricular heterotopia with Ehlers–Danlos syndrome. Neurology 64:254–262

    CAS  PubMed  Google Scholar 

  66. Silverman FN, Gilden JJ (1959) Congenital insensitivity to pain: a neurologic syndrome with bizarre skeletal lesions. Radiology 72:176–190

    CAS  PubMed  Google Scholar 

  67. Steinmann B, Royce PM, Superti-Furga A (1993) The Ehlers–Danlos syndrome. In: Royce PM, Steinmann B (eds) Connective tissues and its heritable disorders: molecular, genetic, and medical aspects. Wiley-Liss, NewYork, pp 351–407

    Google Scholar 

  68. Stewart JM, Gewitz MH, Weldon A, Arlievsky N, Li K, Munoz J (1999) Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics 103:116–121

    Article  CAS  PubMed  Google Scholar 

  69. Thomas P, Bossan A, Lacour JP, Chanalet S, Ortone JP, Chatel M (1996) Ehlers–Danlos syndrome with subependimal periventricular heterotopias. Neurology 46:1165–1167

    CAS  PubMed  Google Scholar 

  70. Tschernogobow A (1892) Cutis laxa Mhft Prakt Dermatol 14:76

    Google Scholar 

  71. Voermans NC, van Alfen N, Pillen S, Lammens M, Schalkwijk J, Zwarts MJ, van Rooij IA, Hamel BCJ, van Engelen BG (2009) Neuromuscular involvement in various types of Ehlers–Danlos syndrome. Ann Neurol 65:687–697

    Article  PubMed  Google Scholar 

  72. Voermans NV, Knoop H, Bleijenberg G, van Engelen BG (2010) Pain in Ehlers–Danlos syndrome is common, severe, and associated with functional impairment. J Pain Symptom Manage. doi:10.1016/j.jpainsymman.2009.12.026

    PubMed  Google Scholar 

  73. Wahab AA, Janahi IA, Eltohami A, Zeid A, Haque NF, Teebi AS (2003) A new type of Ehlers–Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr 92:456–462

    Article  PubMed  Google Scholar 

  74. Wang N, Butler JP, Ingber DE (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1227

    Article  CAS  PubMed  Google Scholar 

  75. Wenstrup RJ, Murad S, Pinnel SR (1989) EDS type VI: clinical manifestation of collagen lysylhydroxylase deifciency. J Pediatr 115:405–409

    Article  CAS  PubMed  Google Scholar 

  76. Yeowell HN, Pinnel SR (1993) The Ehlers–Danlos syndrome. Semin Dermatol 12:229–240

    CAS  PubMed  Google Scholar 

  77. Zaidi SHE, Peltekova V, Meyer S, Lindinger A, Paterson AD, Tsui LC, Faiyaz-UI-Haque M, Teebi AS (2004) A family exhibiting arterial tortuosity syndrome displays homozygosity for markers in the arterial tortuosity locus at chromosome 20q13. Clin Genet 67:183–188

    Article  Google Scholar 

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Savasta, S., Merli, P., Ruggieri, M. et al. Ehlers–Danlos syndrome and neurological features: a review. Childs Nerv Syst 27, 365–371 (2011). https://doi.org/10.1007/s00381-010-1256-1

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