We report on a patient with Klippel-Trenaunay (KT) syndrome, a factor VII deficiency and a copper metabolism disorder. The KT syndrome involved the left leg and, histologically, the liver. Dermatological examination, duplex ultrasonography and a skin and liver biopsy verified the KT syndrome. A long prothrombin time prompted clotting studies revealing a factor VII deficiency while the other factors were in the normal range. Further laboratory examinations showed a copper metabolism disorder similar to Wilson’s disease with a low serum ceruloplasmin level, elevated copper concentration in the urine and increased copper deposition in the liver. Neither liver cirrhosis nor a Kayser-Fleischer corneal ring was present. Sequencing analysis of the Wilson’s disease gene ATB7B showed no mutations. The occurrence of these three uncommon pathologies in a single patient has not been described to date, which may suggest a mutation in a hypothetical common regulatory gene leading to this unusual phenotype.

Keywords:
Klippel-Trenaunay syndrome, Factor VII deficiency, Copper metabolism disorder
1.
Klippel M, Trenaunay P: Du nævus variqueux ostéohypertrophique. Arch Gén Méd 1900;185:641–672.
2.
McKusick VA: Mendelian Inheritance in Man: Catalogs of Human Genes and Genetic Disorders, ed 12. Baltimore, Johns Hopkins University Press, 1998.
3.
Cohen MM Jr: Klippel-Trenaunay syndrome. Am J Med Genet 2000;93:171–175.
4.
Ceballos-Quintal JM, Pinto-Escalante D, Castillo-Zapata I: A new case of Klippel-Trenaunay-Weber (KTW) syndrome: Evidence of autosomal dominant inheritance. Am J Med Genet 1996;63:426–427.
5.
Craven N, Wright AL: Familial Klippel-Trenaunay syndrome: A case report. Clin Exp Dermatol 1995;20:76–79.
6.
Steijlen PM, van Steensel MA: Paradominant inheritance, a hypothesis explaining occasional familial occurrence of sporadic syndromes. Am J Med Genet 1999;85:359–360.
7.
O’Hara PJ, Grant FJ, Haldeman BA, Gray CL, Insley MY, Hagen FS, Murray MJ: Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation. Proc Natl Acad Sci USA 1987;84:5158–5162.
8.
Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW: The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet 1993;5:327–337.
9.
Lindenauer SM: Congenital arteriovenous fistula and the Klippel-Trenaunay syndrome. Ann Surg 1971;174:248–263.
10.
Enjolras O, Mulliken JB: Vascular tumors and vascular malformations (new issues). Adv Dermatol 1997;13:375–423.
11.
Haber M, Reuben A, Burrell M, Oliverio P, Salem RR, West AB: Multiple focal nodular hyperplasia of the liver associated with hemihypertrophy and vascular malformations. Gastroenterology 1995;108:1256–1262.
12.
Ragni MV, Lewis JH, Spero JA, Hasiba U: Factor VII deficiency. Am J Hematol 1981;10:79–88.
13.
Briet E, Onvlee G: Hip surgery in a patient with severe factor VII deficiency. Haemostasis 1987;17:273–277.
14.
McVey JH, Boswell E, Mumford AD, Kemball-Cook G, Tuddenham EG: Factor VII deficiency and the FVII mutation database. Hum Mutat 2001;17:3–17.
15.
Lindenauer SM: The Klippel-Trenaunay syndrome: Varicosity, hypertrophy and hemangioma with no arteriovenous fistula. Ann Surg 1965;162:303–314.
16.
Gibbons RJ, Picketts DJ, Villard L, Higgs DR: Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell 1995;80:837–845.
17.
de Grouchy J, Dautzenberg MD, Turleau C, Beguin S, Chavin-Colin F: Regional mapping of clotting factors VII and X to 13q34: Expression of factor VII through chromosome 8. Hum Genet 1984;66:230–233.
18.
Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM, et al: The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993;5:344–350.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.