Case report| Volume 71, ISSUE 6, P1051-1058, December 1981

Ehlers-Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphysema and cerebral heterotopias

      This paper is only available as a PDF. To read, Please Download here.


      A 30 year old woman with marked joint hypermobility had severe, progressive lung disease, seizures, aneurysms of the sinuses of Valsalva and myocardial infarction documented during life. She died of intractable ventricular fibrillation, and postmortem examination showed myocardial injury in the distribution of the left coronary artery but no occlusive coronary artery disease. Severe panacinar emphysema was found in the lungs. Cerebral heterotopias with peculiar vascularization were present and were a likely cause of the seizure disorder. Electron microscopy showed dermal collagen fibrils to be heterogeneous in size, reduced in number, and irregular and frayed in appearance. This patient had a form of the Ehlers-Danlos syndrome, different from the 10 distinct variants described thus far, associated with lethal internal manifestations.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Hollister DW
        Heritable disorders of connective tissue: Ehlers-Danlos syndrome.
        Pediatr Clin North Am. 1978; 25: 575-592
        • DiFerrante N
        • Leachman RD
        • Angelini P
        • Donnelly PV
        • Francis G
        • Almazan A
        Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V.
        Connect Tissue Res. 1975; 3: 49-53
        • Lichtenstein JR
        • Kohn LD
        • Martin GR
        • Byers P
        • McKusick VA
        Procollagen peptidase deficiency in a form of the Ehlers-Danlos syndrome.
        Trans Assoc Am Phys. 1973; 86: 333-339
        • Pinnell SR
        • Krane SM
        • Kenzora JE
        • Glimcher MJ
        A heritable disorder of connective tissue: hydroxylysine-deficient collagen disease.
        N Engl J Med. 1972; 286: 1013-1020
      1. Hollister DW, Byers PH, Holbrook KA: The Ehlers-Danlos syndromes. In, Harris H, Hirschhorn K, eds: Advances in human genetics. New York: Plenum Press (in press).

        • Steinmann B
        • Gitzelmann R
        • Vogel A
        • Grant ME
        • Harwood R
        • Sear CHJ
        Ehlers-Danlos syndrome in two siblings with deficient lysyl hydroxylase activity in cultured skin fibroblasts but only mild hydroxylysine deficit in skin.
        Helv Paediat Acta. 1975; 30: 255-274
        • Williams B
        • Cranley R
        • Doty S
        • Lichtenstein J
        Morphological observations in connective tissue from individuals with procollagen peptidase deficiency (Ehlers-Danlos type VII syndrome) (abstr).
        Am J Hum Genet. 1973; 25: 86A
        • Vogel A
        • Steinmann B
        Ultrastructural studies of skin from a patient with a new type of Ehlers-Danlos syndrome (EDS) characterized by a structural mutation of procollagen (abstr).
        J Cutan Pathol. 1980; 7: 177
        • Byers PH
        • Siegel RC
        • Holbrook KA
        • Narayanan AS
        • Bornstein P
        • Hall JG
        X-linked cutis laxa. Defective cross-link formation in collagen due to decreased lysyl oxidase activity.
        N Engl J Med. 1980; 303: 61-65
        • Arneson MA
        • Hammerschmidt DE
        • Furcht LT
        • King RA
        A new form of Ehlers-Danlos syndrome: fibronectin corrects defective platelet function.
        JAMA. 1980; 244: 144-147
        • Pope FM
        • Martin GR
        • Lichtenstein JR
        • Penttinen RP
        • Gerson B
        • Rowe DW
        • McKusick VA
        Patients with Ehlers-Danlos syndrome type IV lack type III collagen.
        in: 4th ed. Proc Natl Acad Sci USA. 72. 1975: 1314-1316
        • McKusick VA
        Heritable disorders of connective tissue.
        4th ed. C.V. Mosby, St. Louis1972
        • Beighton P
        Lethal complications of the Ehlers-Danlos syndrome.
        Br Med J. 1968; 3: 656-658
        • Beighton P
        The Ehlers-Danlos syndrome.
        Heinemann Medical Books, London1970
        • Tucker DH
        • Miller DE
        • Jacoby Jr, WJ
        Ehlers-Danlos syndrome with a sinus of Valsalva aneurysm and aortic insufficiency simulating rheumatic heart disease.
        Am J Med. 1963; 35: 715-720
      2. Pyeritz RE: Cardiovascular manifestations of heritable disorders of connective tissue. In, Motulsky AG, Childs B, eds: Progress in medical genetics. Philadelphia: W.B. Saunders (in press).

        • Bulkley BH
        • Hutchins GM
        • Ross RS
        Aortic sinus of Valsalva aneurysms simulating primary right-sided valvular heart disease.
        Circulation. 1975; 52: 696-699
        • Merten DF
        • Rooney R
        Progressive pulmonary emphysema associated with congenital generalized elastolysis (cutis laxa).
        Radiology. 1974; 113: 691-692
        • Reye RDK
        • Bale PM
        Elastic tissue in pulmonary emphysema in Marfan syndrome.
        Arch Pathol. 1973; 96: 427-431
        • Pope FM
        • Nicholls AC
        Molecular abnormalities of collagen.
        J Clin Pathol. 1978; 12 (Royal Coll Pathol): 95-104
        • Wechsler HL
        • Fisher ER
        Ehlers-Danlos syndrome. Pathologic, histochemical, and electron microscopic observations.
        Arch Pathol. 1965; 77: 613-619
        • Vogel A
        • Holbrook KA
        • Steinmann B
        • Gitzelmann R
        • Byers BH
        Abnormal collagen fibril structure in the gravis form (Type I) of Ehlers-Danlos syndrome.
        Lab Invest. 1979; 40: 201-206
        • Sevenich M
        • Schultz-Ehrenburg U
        • Orfanos CE
        Ehlers-Danlos syndrome: eine Fibroblasten-und Kollagenkrankheit: Typisiering und elektronenmikroskopische Befunde bei fünf Kranken.
        Arch Dermatol Res. 1980; 267: 237-251
        • Black CM
        • Gathercole U
        • Bailey AJ
        • Beighton P
        The Ehlers-Danlos syndrome: an analysis of the structure of the collagen fibres of the skin.
        Br J Dermatol. 1980; 102: 85-96
        • Byers PH
        • Holbrook KA
        • McGillivray B
        • MacLeod PM
        • Lowry RB
        Clinical and ultrastructural heterogeneity of Type IV Ehlers-Danlos syndrome.
        Hum Genet. 1979; 47: 141-150
        • Lillie JH
        • MacCallum DK
        • Scaletta LJ
        • Occhino JC
        Collagen structure: evidence for a helical organization of the collagen fibril.
        J Ultrastrucl Res. 1977; 58: 134-143
        • Kischer CW
        • Droegemueller W
        • Shetlar M
        • Chvapil M
        • Vining J
        Ultrastructural changes in the architecture of collagen in the human cervix treated with urea.
        Am J Pathol. 1980; 99: 528-538
        • Oegeman Jr, TR
        • Laidlaw J
        • Hascall VC
        • Dziewiatkowski DD
        The effect of proteoglycans on the formation of fibrils from collagen solutions.
        Arch Biochem Biophys. 1975; 170: 698-709
        • Minor RR
        Collagen metabolism: a comparison of diseases of collagen and diseases affecting collagen.
        Am J Pathol. 1980; 98: 227-280
        • Horton WA
        • Collins DL
        • DeSmet AA
        • Kennedy JA
        • Schimke RN
        Familial joint instability syndrome.
        Am J Med Genet. 1980; 6: 221-228
        • Siegel RC
        • Black CM
        • Barley AJ
        Cross-linking of collagens in the x-linked Ehlers-Danlos type V.
        Biochem Biophys Res Comm. 1979; 88: 218-287