[en] Ehlers-Danlos syndrome (EDS) dermatosparaxis type (type VIIC) and the related disease of cattle dermatosparaxis, are recessively inherited connective tissue disorders, caused by a deficient activity of procollagen I N-proteinase, the enzyme that excises the N-terminal propeptide in procollagen type I, type II, and type III. Although well documented in cattle, to date only seven human cases have been recorded, most of them aged under 2 years. We document the natural history of three patients with EDS dermatosparaxis type, two of whom have been reported before the age of 2 years, and one new patient. The phenotype of the patients, and especially the facial resemblance, is striking, making this a clinically recognizable condition. The most consistent anomalies during the first years of life are premature rupture of the membranes, extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. The children are at risk for rupture of internal organs due to soft tissue fragility, as is illustrated by different internal events in two of the three patients described here. Orofacial features include micrognathia, a frontal open bite, and gingival hyperplasia with varying degrees of hyperkeratosis. The deciduous dentition shows abnormal morphology of the molars, obliteration of the tooth pulp, and severe enamel attrition. The permanent dentition shows agenesis and microdontia of several teeth. Tooth discoloration, dysplastic roots, and tooth pulp obliteration are present in a restricted number of permanent teeth.
Disciplines :
Genetics & genetic processes Dermatology
Author, co-author :
Malfait, Fransiska; Ghent University Hospital > Center for Medical Genetics
De Coster, Peter; Ghent University Hospital > Dpt of Paediatric Dentistry > Center for Special Care, Paecamed Research
Hausser, Ingrid; University of Heidelberg - Germany > Dpt of Dermatology > Electron Microscopic Laboratory
van Essen, Anthonie J; University Hospital of Groningen - The Netherlands > Dpt of Clinical Genetics
Franck, Peter; University Hospital Freiburg - Germany > Center for Paediatrics and Youth Medicine
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de BIologie des Tissus Conjonctifs
Martens, Luc; Ghent University Hospital > Dpt of Paediatric Dentistry > Center for Special Care, Paecamed Research
De Paepe, Anne; University Hospital Ghent > Center for Medical Genetics
Language :
English
Title :
The natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC).
Publication date :
2004
Journal title :
American Journal of Medical Genetics. Part A
ISSN :
1552-4825
eISSN :
1552-4833
Publisher :
Wiley Liss, Inc., Hoboken, United States - New Jersey
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. 1998. Ehlers-Danlos syndromes: Revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 77:31-37.
Colige A, Li SW, Sieron AL, Nusgens BV, Prockop DJ, Lapiere CM. 1997. cDNA cloning and expression of bovine procollagen I N-proteinase: A new member of the superfamily of zinc-metalloproteinases with binding sites for cells and other matrix components. Proc Natl Acad Sci USA 94:2374-2379.
Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, Wilcox W, Krakow D, Cohn DH, Reardon W, Byers PH, Lapiere CM, Prockop DJ, Nusgens BV. 1999. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet 65:308-317.
Colige A, Nuytinck L, Hausser I, van Essen AJ, Thiry M, Herens C, Adès LC, Malfait F, De Paepe A, Franck P, Wolff G, Oosterwijk JC, Smitt JHS, Lapière CM, Nusgens BV. 2004. Common polymorphisms and novel types of mutation in the ADAMTS2 gene responsible for the dermatosparaxis type of Ehlers-Danlos (type VIIC). J Invest Dermatol, in press.
De Coster PJ, Malfait F, Martens LC, De Paepe A. 2003. Unusual oral findings in dermatosparaxis (Ehlers-Danlos syndrome type VIIC). J Oral Pathol Med 32(9):568-570.
Fujimoto A, Wilcox WR, Cohn DH. 1997. Clinical, morphological, and biochemical phenotype of a new case of Ehlers-Danlos syndrome type VIIC. Am J Med Genet 68:25-28.
Gage JP, Shaw RM, Moloney FB. 1995. Collagen type in dysfunctional temporomandibular joint disks. J Prosthet Dent 74:517-520.
Helle O, Nes NN. 1972. A hereditary skin defect in sheep. Acta Vet Scand 13:443-445.
Holbrook KA, Byers PH, Counts DF, Hegreberg GA. 1980. Dermatosparaxis in a Himalayan cat: II. Ultrastructural studies of dermal collagen. J Invest Dermatol 74:100-104.
Li SW, Arita M, Fertala A, Bao Y, Kopen GC, Langsjo TK, Hyttinen MM, Helminen HJ, Prockop DJ. 2001. Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility. Biochem J 355(Pt 2):271-278.
Lukinmaa PL, Ranta H, Ranta K, Kaitila I. 1987a. Dental findings in osteogenesis imperfecta: I. Occurrence and expression of type I dentinogenesis imperfecta. J Craniofac Genet Dev Biol 7:115-125.
Lukinmaa PL, Ranta H, Ranta K, Kaitila I, Hietanen J. 1987b. Dental findings in osteogenesis imperfecta: II. Dysplastic and other developmental defects. J Craniofac Genet Dev Biol 7:127-135.
Nusgens BV, Verellen-Dumoulin C, Hermanns-Le T, De Paepe A, Nuytinck L, Pierard GE, Lapiere CM. 1992. Evidence for a relationship between Ehlers-Danlos type VII C in humans and bovine dermatosparaxis. Nat Genet 1:214-217.
Pasch MC, Sillevis Smitt JH, Veenhuizen L, Kuiters GR, van Essen AJ. 2000. Boy with dermatosparaxis (Ehlers-Danlos type VIIC). Ned Tijdschr Geneeskd 144:2435-2436.
Petty EM, Seashore MR, Braverman IM, Spiesel SZ, Smith LT, Milstone LM. 1993. Dermatosparaxis in children. A case report and review of the newly recognized phenotype. Arch Dermatol 129:1310-1315.
Pierard GE, Lapiere M. 1976. Skin in dermatosparaxis. Dermal micro-architecture and biomechanical properties. J Invest Dermatol 66:2-7.
Ranta H, Lukinmaa PL, Waltimo J. 1993. Heritable dentin defects: Nosology, pathology, and treatment. Am J Med Genet 45:193-200.
Reardon W, Winter RM, Smith LT, Lake BD, Rossiter M, Baraitser M. 1995. The natural history of human dermatosparaxis (Ehlers-Danlos syndrome type VIIC). Clin Dysmorphol 4:1-11.
Schwartz S, Tsipouras P. 1984. Oral findings in osteogenesis imperfecta. Oral Surg Oral Med Oral Pathol 57(2):161-167.
Smith LT, Wertelecki W, Milstone LM, Petty EM, Seashore MR, Braverman IM, Jenkins TG, Byers PH. 1992. Human dermatosparaxis: A form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen. Am J Hum Genet 51:235-244.
Steinmann B. 2002. Connective tissue and its heritable disorders, 2nd edn. In: Royce P, Steinmann B, editors. New York: Wiley-Liss, Inc. 1201p.
Wang WM, Lee S, Steiglitz BM, Scott IC, Lebares CC, Alien ML, Brenner MC, Takahara K, Greenspan DS. 2003. Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase. J Biol Chem 278:19549-19557.
Wertelecki W, Smith LT, Byers P. 1992. Initial observations of human dermatosparaxis: Ehlers-Danlos syndrome type VIIC. J Pediatr 121:558-564.