Other entities represented in this entry:
SNOMEDCT: 109380002, 82385007; ICD10CM: I82.0; ICD9CM: 453.0; ORPHA: 131; DO: 11512;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q24.2 | {Budd-Chiari syndrome} | 600880 | Autosomal recessive | 3 | F5 | 612309 |
| 9p24.1 | {Budd-Chiari syndrome, somatic} | 600880 | 3 | JAK2 | 147796 |
A number sign (#) is used with this entry because susceptibility to Budd-Chiari syndrome (BDCHS) can result from heterozygous or homozygous mutation in the F5 gene (612309) on chromosome 1q24 or by somatic mutation in the JAK2 gene (147796) on chromosome 9p24.
Budd-Chiari syndrome (BDCHS) is defined as thrombosis of one or more of the large hepatic veins, the inferior vena cava, or both. Patients present with a classic clinical triad of abdominal pain, hepatomegaly, and ascites, typically associated with nonspecific elevations of liver enzymes. The disorder may be acute, subacute, or chronic. Edema of the legs may be present (summary by Chung et al., 2006).
Budd-Chiari syndrome (BDCHS) is characterized by a spectrum of disease states, including anatomic abnormalities and hypercoagulable disorders, resulting in hepatic venous outflow occlusion. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain, and abdominal ascites (Zimmerman et al., 2006).
One of the causes of Budd-Chiari syndrome is a membranous obstruction of the inferior vena cava (MOVC). Primary thrombosis due to a thrombophilia such as that resulting from defects in the natural coagulation inhibitors such as protein C (612283), protein S (176880), and antithrombin III (107300) are also causes. Riemens et al. (1995) reported a family in which 3 of 11 sibs (2 sisters and 1 brother) showed symptoms of MOVC developing in early adult life. All had signs of more longstanding disease, as judged by the presence of collaterals, cirrhosis, and, in one case, hepatocellular carcinoma. The brother died with lung metastasis from the hepatocellular carcinoma, while the 2 sisters had surgical removal of the membrane and were well 20 and 21 years after surgery. On family screening, no further cases of membranous obstruction of the inferior vena cava were found. There was no evidence of an inherited defect in a coagulation inhibitor or plasminogen deficiency (173350); however, Riemens et al. (1995) could not totally exclude a thrombotic etiology.
Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera (PV; 263300). Cario et al. (2003) described a third pediatric case of Budd-Chiari syndrome as the initial symptom of familial polycythemia vera in an 11-year-old girl; the patient's grandmother also had polycythemia vera. The patient's mother was unaffected. The patient underwent orthotopic liver transplantation and the polycythemia vera was treated with hydroxyurea. In agreement with the clinical diagnosis, the polycythemia rubra vera-1 gene (PRV1; 162860) showed increased mRNA expression in peripheral granulocytes.
Menon et al. (2004) reviewed all aspects of Budd-Chiari syndrome, including the inherited hypercoagulable states that had been found to be associated with the disorder. They noted that the relative risk of hepatic vein thrombosis among women who use oral contraceptives is 2.37, which is similar to their relative risk of stroke, myocardial infarction, and venous thromboembolism (Valla et al., 1986). Many patients in whom Budd-Chiari syndrome develops in association with the use of oral contraceptives or pregnancy also have an underlying thrombophilia, either inherited or acquired.
Mahmoud et al. (1997) reported the incidence of the factor V Leiden mutation (R506Q; 612309.0001) in Budd-Chiari syndrome and portal vein thrombosis. The R506Q mutation was seen in 7 (23%) of 30 patients with Budd-Chiari syndrome (6 heterozygotes and 1 homozygote), 3 of whom had coexistent myeloproliferative disease. Only 1 (3%) of 32 patients with portal vein thrombosis was found to have the R506Q mutation. The mutation was found in 3 (6%) of the 54 controls, who had liver disease but no history of thrombophilia. Mahmoud et al. (1997) concluded that the R506Q mutation seems to be an important factor in the pathogenesis of Budd-Chiari syndrome but not of portal vein thrombosis.
Gurakan et al. (1999) described a child with Budd-Chiari syndrome who was homozygous for the factor V Leiden mutation. Budd-Chiari syndrome is rare in children.
Janssen et al. (2000) compared 43 patients with Budd-Chiari syndrome and 92 patients with portal vein thrombosis with 474 population-based controls. The relative risk of Budd-Chiari syndrome was 11.3 for individuals with the factor V Leiden mutation, 2.1 for those with a prothrombin (176930) gene mutation, and 6.8 for those with protein C deficiency. In patients with portal vein thrombosis, the corresponding figures were 2.7, 1.4, and 4.6, respectively. The relative risk of Budd-Chiari syndrome or portal vein thrombosis was not increased in the presence of inherited protein S or antithrombin deficiency.
Patel (2005) identified a V617F mutation in the JAK2 gene (147796.0001) in a high proportion of patients with the Budd-Chiari syndrome, providing evidence that these patients have a latent myeloproliferative disorder. Chung et al. (2006) described Budd-Chiari syndrome in a 46-year-old woman who was well until the onset of increasing abdominal distention over a period of several days. She was found to have a combination of the JAK2 V617F mutation and the factor V Leiden mutation.
Sozer et al. (2009) identified somatic homozygous JAK2 V617F mutations in liver venule endothelial and hematopoietic cells from 2 unrelated patients with polycythemia vera who developed Budd-Chiari syndrome. However, analysis of endothelial cells from a third PV patient with Budd-Chiari syndrome and in 2 patients with hepatoportal sclerosis without PV showed only wildtype JAK2. Endothelial and hematopoietic cells are believed to come from a common progenitor called the hemangioblast. Sozer et al. (2009) concluded that finding V617F-positive endothelial cells and hematopoietic cells from patients with PV who developed Budd-Chiari syndrome indicates that endothelial cells are involved by the PV malignant process, and suggested that the disease might originate from a common cell of origin in some patients.
Cario, H., Pahl, H. L., Schwarz, K., Galm, C., Hoffmann, M., Burdelski, M., Kohne, E., Debatin, K.-M. Familial polycythemia vera with Budd-Chiari syndrome in childhood. Brit. J. Haemat. 123: 346-352, 2003. [PubMed: 14531919] [Full Text: https://doi.org/10.1046/j.1365-2141.2003.04591.x]
Chung, R. T., Iafrate, A. J., Amrein, P. C., Sahani, D. V., Misdraji, J. Case 15-2006: a 46-year-old woman with sudden onset of abdominal distention. New Eng. J. Med. 354: 2166-2175, 2006. [PubMed: 16707754] [Full Text: https://doi.org/10.1056/NEJMcpc069006]
Gurakan, F., Gurgey, A., Bakkaloglu, A., Kocak, N. Homozygous factor V Leiden mutation in a child with Budd-Chiari syndrome. J. Pediat. Gastroent. Nutr. 28: 516-517, 1999. [PubMed: 10328130] [Full Text: https://doi.org/10.1097/00005176-199905000-00016]
Janssen, H. L. A., Meinardi, J. R., Vleggaar, F. P., van Uum, S. H. M., Haagsma, E. B., van der Meer, F. J. M., van Hattum, J., Chamuleau, R. A. F. M., Adang, R. P., Vandenbroucke, J. P., van Hoek, B., Rosendaal, F. R. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 96: 2364-2368, 2000. [PubMed: 11001884]
Mahmoud, A. E. A., Elias, E., Beauchamp, N., Wilde, J. T. Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis. Gut 40: 798-800, 1997. [PubMed: 9245936] [Full Text: https://doi.org/10.1136/gut.40.6.798]
Menon, K. V. N., Shah, V., Kamath, P. S. The Budd-Chiari syndrome. New Eng. J. Med. 350: 578-585, 2004. [PubMed: 14762185] [Full Text: https://doi.org/10.1056/NEJMra020282]
Patel, R. K. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. (Abstract) Proceedings of the 47th Annual Meeting of the American Society of Hematology, Atlanta 2005. P. 7282.
Riemens, S. C., Haagsma, E. B., Kok, T., Gouw, A. S. H., van der Jagt, E. J. Familial occurrence of membranous obstruction of the inferior vena cava: arguments in favor of a congenital etiology. J. Hepatol. 22: 404-409, 1995. [PubMed: 7665859] [Full Text: https://doi.org/10.1016/0168-8278(95)80102-2]
Sozer, S., Fiel, M. I., Schiano, T., Xu, M., Mascarenhas, J., Hoffman, R. The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood 113: 5246-5249, 2009. [PubMed: 19293426] [Full Text: https://doi.org/10.1182/blood-2008-11-191544]
Valla, D., Le, M. G., Poynard, T., Zucman, N., Rueff, B., Benhamou, J. P. Risk of hepatic vein thrombosis in relation to recent use of oral contraceptives: a case-control study. Gastroenterology 90: 807-811, 1986. [PubMed: 3949113] [Full Text: https://doi.org/10.1016/0016-5085(86)90855-3]
Zimmerman, M. A., Cameron, A. M., Ghobrial, R. M. Budd-Chiari syndrome. Clin. Liver Dis. 10: 259-273, 2006. [PubMed: 16971261] [Full Text: https://doi.org/10.1016/j.cld.2006.05.005]