Alternative titles; symbols
SNOMEDCT: 403833009; ORPHA: 32960; DO: 0090018;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12p13.31 | Periodic fever, familial | 142680 | Autosomal dominant | 3 | TNFRSF1A | 191190 |
A number sign (#) is used with this entry because of evidence that autosomal dominant familial periodic fever (FPF) is caused by heterozygous mutation in the tumor necrosis factor receptor-1 gene (TNFRSF1A; 191190) on chromosome 12p13.
Familial periodic fever (FPF) is an autoinflammatory disorder characterized by recurrent fever with localized myalgia and painful erythema. Febrile attacks may last 1 or 2 days but often last longer than 1 week. Arthralgia of large joints, abdominal pain, conjunctivitis, and periorbital edema are common features. During attacks, painless cutaneous lesions may develop on the trunk or extremities and may migrate distally (review by Drenth and van der Meer, 2001).
Williamson et al. (1982) described an Irish-Scottish family with an autosomal dominant 'periodic disease' characterized by recurrent attacks of fever, abdominal pain, localized tender skin lesions, and myalgia. Pleurisy, leukocytosis, and high erythrocyte sedimentation rate were other features. The disease pursued a benign course and no patient had developed amyloidosis. At least 13 persons in 5 sibships of 3 generations were affected, with 4 instances of male-to-male transmission. The disorder in this family was termed 'familial Hibernian fever.'
Bouroncle and Doan (1957) described 12 cases of periodic fever in 6 sibships in 5 generations of a family. No abnormality was detected by clinical examinations during and between attacks or by many laboratory studies.
Wang et al. (1999) reported a 10-year-old Ashkenazi Jewish boy who developed lymphadenopathy at age 11 months, followed by bouts of prolonged fever, splenomegaly, elevated sedimentation rate, anemia, and reticulocytosis. At age 3 years, he had noninfectious lymphocytic meningitis followed by optic neuritis, indicating a pattern of disparate inflammatory conditions. At the time of report, he exhibited adenopathy and splenomegaly. Autoantibodies were not detected, but lymphocyte phenotyping showed a dramatic T and B lymphocytosis and increased CD4-, CD8- T cells, especially a striking increase in CD4-, CD8- gamma/delta T cells. Both parents were clinically normal. Although the boy was originally diagnosed with autoimmune lymphoproliferative syndrome type IIA (ALPS2A; 603909), he was later found to have a pathogenic mutation in the TNFRSF1A gene, consistent with a diagnosis of TRAPS (Zhu et al., 2006).
Toro et al. (2000) described the cutaneous features of 25 patients with clinically and molecularly diagnosed FPF, which they referred to as 'tumor necrosis factor receptor-associated periodic syndrome' (TRAPS). Twenty-one patients (84%) had cutaneous manifestations. Migratory macules and patches were the most common findings. In addition, 10 patients (40%) exhibited erythematous edematous plaques. Lesions usually occurred during febrile episodes, were most commonly seen on the extremities, were often associated with myalgia, and lasted 4 to 21 days. Biopsies of lesional skin were obtained from 10 patients. The histologic findings were nonspecific, consisting of infiltrating T lymphocytes and monocytes, and could not be distinguished from a viral exanthem or serum sickness-like reaction.
Wildemann et al. (2007) reported a man with periodic fever syndrome who developed central nervous system involvement. Since childhood, he had experienced recurrent attacks of fever, myalgias, arthralgias, and painful migratory rashes. At age 38, he developed brainstem and cerebellar symptoms from a T-cell predominant inflammatory infiltrate without evidence of demyelination. Treatment with a TNF-alpha antagonist resulted in marked clinical improvement with mild residual symptoms. Genetic analysis identified a heterozygous mutation in the TNFRSF1A gene (C55A; 191190.0012).
The transmission pattern of FPF in the families reported by McDermott et al. (1999) was consistent with autosomal dominant inheritance.
Weyhreter et al. (2003) reported a Danish family with TRAPS in which the youngest affected member was treated successfully with etanercept (a fusion protein of the extracellular domain of TNFRSF1A and the Fc portion of IgG1) at age 18 months following lack of response to infliximab or of a sustained response to prednisolone.
Mulley et al. (1997, 1998) found frequent recombination of FPF with the marker D16S2622 located within 1 Mb of familial Mediterranean fever at 16p13.3, thus excluding allelism between these clinically similar conditions. By a genomewide search, they detected linkage to a cluster of markers at 12p13, with a multipoint lod score of 6.14 at D12S356. Assuming penetrance of 90%, they assigned the relevant gene (symbolized FPF by them) to a 19-cM interval between D12S314 and D12S364.
McDermott et al. (1998) confirmed the assignment of familial Hibernian fever to 12p13 by studies in the originally reported Irish-Scottish family (6:Williamson et al., 1982) and in 2 Irish families with similar clinical features (Quane et al., 1997). Cumulative multipoint linkage analyses indicated that the gene, which they symbolized FHF (in parallel with the FMF of familial Mediterranean fever), is likely to be located in an 8-cM interval between D12S77 and D12S356, with a maximum lod score of 3.79. The 2-point maximum lod score was 3.11 for D12S77. There was no evidence of genetic heterogeneity in these 3 families.
In affected members of families segregating periodic fever, McDermott et al. (1999) identified germline mutations in the TNFRSF1A gene (191190.0001-191190.0006), which had been identified as a candidate gene by linkage studies. The families studied included those reported by Mulley et al. (1998) and McDermott et al. (1998), a Finnish family reported by Karenko et al. (1992), and 3 small North American families of Irish/English/German, Irish, and French-Canadian ancestry.
Aganna et al. (2001) identified a mutation in the TNFRSF1A gene (191190.0007) in a 2-generation Dutch family with TRAPS. The mutation was present in the affected father and in all of his 4 children (the affected proposita, a mildly affected son, and 2 unaffected children) but was not found in 120 control chromosomes from unaffected Dutch individuals. Low soluble plasma levels of TNFRSF1A segregated with the mutation in all the children, including those who were unaffected. The authors suggested that low levels of soluble TNFRSF1A in combination with particular environmental insults may be necessary to produce the full-blown phenotype. They also raised the possibility that TNFRSF1A mutations may be present in mildly symptomatic or indeed asymptomatic persons.
According to Kastner (2003), the gene for 'Hibernian fever' came from the Scottish (mother's) side of the family; hence, it should be called Caledonian fever rather than Hibernian fever.
In 2 brothers with periodic fever, Driesen et al. (1968) found that the nonesterified etiocholanolone level of the blood was raised not only during febrile attacks but also in fever-free periods. A sister had attacks of fever of unexplained origin accompanied by abdominal pain and rash but had no symptoms after menarche. Drenth et al. (1994) included the family of Driesen et al. (1968) in a series of cases of the hyper-IgD syndrome (260920). They stated that measurements on subsequent occasions in both brothers showed normal values of etiocholanolone.
Aganna, E., Aksentijevich, I., Hitman, G. A., Kastner, D. L., Hoepelman, A. I. M., Posma, F. D., Zweers, E. J. K., McDermott, M. F. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Dutch family: evidence for a TNFRSF1A mutation with reduced penetrance. Europ. J. Hum. Genet. 9: 63-66, 2001. [PubMed: 11175303] [Full Text: https://doi.org/10.1038/sj.ejhg.5200573]
Bouroncle, B. A., Doan, C. A. 'Periodic fever': occurrence in five generations. Am. J. Med. 23: 502-506, 1957. [PubMed: 13458215] [Full Text: https://doi.org/10.1016/0002-9343(57)90330-3]
Drenth, J. P. H., Haagsma, C. J., van der Meer, J. W. M., the International Hyper-IgD Study Group. Hyperimmunoglobulinemia D and periodic fever syndrome: the clinical spectrum in a series of 50 patients. Medicine 73: 133-144, 1994. [PubMed: 8190036]
Drenth, J. P. H., van der Meer, J. W. M. Hereditary periodic fever. New Eng. J. Med. 345: 1748-1757, 2001. [PubMed: 11742050] [Full Text: https://doi.org/10.1056/NEJMra010200]
Driesen, O., Voute, P. A., Jr., Vermeulen, A. A description of two brothers with permanently raised non-esterified aetiocholanolone blood level. Acta Endocr. 57: 177-186, 1968. [PubMed: 4229818] [Full Text: https://doi.org/10.1530/acta.0.0570177]
Karenko, L., Pettersson, T., Roberts, P. Autosomal dominant 'Mediterranean fever' in a Finnish family. J. Intern. Med. 232: 365-369, 1992. Note: Erratum: J. Intern. Med. 233: 101 only, 1993. [PubMed: 1402641] [Full Text: https://doi.org/10.1111/j.1365-2796.1992.tb00600.x]
Kastner, D. L. Personal Communication. Bethesda, Md. 1/27/2003.
McDermott, M. F., Aksentijevich, I., Galon, J., McDermott, E. M., Ogunkolade, B. W., Centola, M., Mansfield, E., Gadina, M., Karenko, L., Pettersson, T., McCarthy, J., Frucht, D. M., and 21 others. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97: 133-144, 1999. [PubMed: 10199409] [Full Text: https://doi.org/10.1016/s0092-8674(00)80721-7]
McDermott, M. F., Ogunkolade, B. W., McDermott, E. M., Jones, L. C., Wan, Y., Quane, K. A., McCarthy, J., Phelan, M., Molloy, M. G., Powell, R. J., Amos, C. I., Hitman, G. A. Linkage of familial Hibernian fever to chromosome 12p13. Am. J. Hum. Genet. 62: 1446-1451, 1998. [PubMed: 9585614] [Full Text: https://doi.org/10.1086/301886]
Mulley, J., Saar, K., Hewitt, G., Ruschendorf, F., Phillips, H., Colley, A., Sillence, D., Reis, A., Wilson, M. Gene localisation for an autosomal dominant familial periodic fever. (Abstract) Am. J. Hum. Genet. 61 (suppl.): A287 only, 1997.
Mulley, J., Saar, K., Hewitt, G., Ruschendorf, F., Phillips, H., Colley, A., Sillence, D., Reis, A., Wilson, M. Gene localization for an autosomal dominant familial periodic fever to 12p13. Am. J. Hum. Genet. 62: 884-889, 1998. [PubMed: 9529351] [Full Text: https://doi.org/10.1086/301793]
Quane, K. A., McDermott, M. F., McCarthy, J., Daly, M., Phelan, M., Davey, S. R., Sachs, J. A., Hitman, G. A., Shanahan, F., Molloy, M. G. Autosomal dominant periodic fever in two Irish pedigrees. (Abstract) Brit. J. Rheum. 36 (suppl. 1): 142 only, 1997.
Toro, J. R., Aksentijevich, I., Hull, K., Dean, J., Kastner, D. Tumor necrosis factor receptor-associated periodic syndrome: a novel syndrome with cutaneous manifestations. Arch. Derm. 136: 1487-1494, 2000. [PubMed: 11115159] [Full Text: https://doi.org/10.1001/archderm.136.12.1487]
Wang, J., Zheng, L., Lobito, A., Chan, F. K., Dale, J., Sneller, M., Yao, X., Puck, J. M., Straus, S. E., Lenardo, M. J. Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 98: 47-58, 1999. [PubMed: 10412980] [Full Text: https://doi.org/10.1016/S0092-8674(00)80605-4]
Weyhreter, H., Schwartz, M., Kristensen, T. D., Valerius, N. H., Paerregaard, A. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family. J. Pediat. 142: 191-193, 2003. [PubMed: 12584543] [Full Text: https://doi.org/10.1067/mpd.2003.15]
Wildemann, B., Rudofsky, G., Jr., Kress, B., Jarius, S., Konig, F., Schwenger, V. The tumor necrosis factor-associated periodic syndrome, the brain, and tumor necrosis factor-A antagonists. Neurology 68: 1742-1744, 2007. [PubMed: 17360963] [Full Text: https://doi.org/10.1212/01.wnl.0000260226.21010.2b]
Williamson, L. M., Hull, D., Mehta, R., Reeves, W. G., Robinson, B. H. B., Toghill, P. J. Familial hibernian fever. Quart. J. Med. 51: 469-480, 1982. [PubMed: 7156325]
Zhu, S., Hsu, A. P., Vacek, M. M., Zheng, L., Schaffer, A. A., Dale, J. K., Davis, J., Fischer, R. E., Straus, S. E., Boruchov, D., Saulsbury, F. T., Lenardo, M. J., Puck, J. M. Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome. Hum. Genet. 119: 284-294, 2006. [PubMed: 16446975] [Full Text: https://doi.org/10.1007/s00439-006-0138-9]