The author: Professor Yasser Metwally
December 15, 2012 — Ehlers-Danlos syndrome constitutes a group of connective tissue disorders characterized by clinical and genetic variability. Mutations in 8 separate genes contribute to these phenotypes. Earlier reports were focused on the skin and ocular abnormalities. The heterogeneity began to be appreciated in the past few decades, from the insights gained from biochemical and molecular genetic studies.
Ehlers-Danlos syndrome type 1 has an autosomal dominant inheritance and affected individuals have soft, velvety, hyperextensible skin, joint hypermobility, easy bruisablility and thin, atrophic ‘cigarette-paper’ scars following trauma. About 50% of the infants with EDS 1 are born 4 to 8 weeks prematurely because of the fragile fetal membranes as in our Patient 3.  Neurological manifestation other than stroke and hypotonia include peripheral neuropathy, epilepsy, neuronal migration disorders,[3,6] Melkerson – Rosenthal syndrome, familial spastic ataxia and dentatopallido luysian atrophy. EDS has a prevalence of 1 in 10,000 persons. It is therefore possible that these neurological illnesses coexist rather than causally linked. Rare manifestations like neuropathy, optic atrophy, deafness, cerebellar ataxia, chorea, myotonia, calf hypertrophy, polymicrogyria and mirror movements ale also noted.
Defects in extra cellular matrix proteins have been proposed as a mechanism for arterial aneurysms and EDS IV. Disruption between the extracellular matrix and cytoskeleton causes aberrations in cellular migration. This might result in various congenital malformations of the brain parenchyma like neuronal migration disorders. The extracellular matrix proteins involved may affect collagen or tenascins, a family of glycoproteins expressed in the surface of neurons and glial cells. Mice deficient in small leucine rich proteoglycans develop osteoporosis, EDS, muscular dystrophy and corneal diseases. This may be the link between some cases of muscular dystrophy and EDS.
Ehlers-Danlos syndrome may affect all level of neuraxis. A careful search may reveal asymptomatic and unrecognized abnormalities, which offer better explanations for the patient’s symptoms and may alter prognosis.
1. Byers PH. Disorders of collagen biosynthesis and structure. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw Hill; 1995;5241-71.
2. Pretorius ME, Butler IJ. Neurologic manifestations of Ehlers-Danlos syndrome. Neurology 1983;33:1087-89.
3. Thomas P, Bossan A, Lacour JP, Chanalet S, Ortonne JP, Chatel M. Ehlers-Danlos syndrome with subependymal periventricular heterotopias. Neurology 1996;46:1165-67.
4. Muellbacher W, Finisterer J, Mamoli B, Bittner RE, Trautinger F. Axonal neuropathy in Ehlers -Danlos syndrome. Muscle Nerve 1998; 21:972-4.
5. Jacome DE. Epilepsy in Ehlers – Danlos Syndrome. Epilepsia 1999;40:467-73.
6. Echaniz-Laguna A, de Saint-Martin A, Lafontaine A L, Tasch E, Thomas P, Hirsh E et al. Bilateral Focal Polymicrogyria in Ehlers – Danlos syndrome. Arch Neurol 2000;57:123-7.
7. Caksen H, Cesur Y, Tombul T, Uner A, Kirimi E, Tuncer O et al. A case of Melkersson-Rosenthal syndrome associated with Ehlers – Danlos syndrome. Genet Couns 2002;13:183-6.
8. Chouza C, Caamano JL, De Medina O, Bogacz J, Oehninger C, Vignale R et al. Familial spastic ataxia associated with Ehlers-Danlos syndrome with platelet dysfunction. Can J Neurol Sci 1984;11:541-549.
9. Sugie K, Nakamuro T, Harada N, Suzumura A, Takayanagi T. A report of two siblings with both maternal dentate-rubro – pallido – luysian atrophy and paternal Ehlers – Danlos syndrome type III. Rinsho Shinkeigaku 1998;38:233-7.
10. North KN, Whiteman DAH, Pepin MG, Byers PH. Cerebrovascular complications in Ehlers-Danlos syndrome type IV. Ann Neurol 1995;38:960-4.
11. Ameye L, Young MF. Mice deficient in small leucine – rich proteoglycans: novel in vivo model for osteoporosis, Ehlers – Danlos syndrome, muscular dystrophy and corneal disease. Glycobiology 2002;12:107-16