Also Known as:
- Cinca Syndrome;
- Chronic Neurologic Cutaneous and Articular Syndrome;
- Multisystem Inflammatory Disease, Neonatal-Onset;
- NOMID Cryopyrin-Associated Periodic Syndrome 3, CAPS 3
Description
Chronic infantile neurologic cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy (Feldmann et al., 2002).
See also familial cold autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with a less severe phenotype.
Clinical Features
CINCA syndrome, also known as ‘neonatal onset multisystem inflammatory disease,’ or NOMID, is a rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation (Prieur and Griscelli, 1981; Hassink and Goldsmith, 1983; Torbiak et al., 1989; Prieur, 2001). Persistent and migratory skin rash associated with skin perivascular polymorphonuclear infiltrates is present in patients, starting at birth. A progressive neurologic impairment results from chronic meningitis caused by polymorphonuclear cell infiltration. A progressive visual defect and perceptive deafness frequently occur with increasing age. Joint symptoms manifest recurrent joint flares with or without severe radiologically evident modifications involving the growth cartilage or bone epiphysis. Distinctive facies with characteristic frontal bossing and protruding eyes have been described, as well as shortening of distal limbs and growth retardation, giving a sib-like resemblance between unrelated patients. Intrafamilial occurrence, although much rarer than sporadic cases, is suggestive of an autosomal dominant inheritance pattern (Feldmann et al., 2002).
Overgrowth of the patella and distal femur create a prominence of the knees that is characteristic of CINCA syndrome. This particular feature was noted in the report of Prieur and Griscelli (1981) and the review of Prieur et al. (1987) with clinical photographs and radiographs. Prieur et al. (1987) reported on the clinical presentation and course of 30 patients with CINCA syndrome observed in France, Germany, Finland, England, and the United States.
Leone et al. (2003) studied 3 patients with CINCA syndrome and found that all showed normal phagocytosis and oxidative burst functions of neutrophils. Because the patients had significantly increased expression of CD10 (120520), Leone et al. (2003) postulated that this finding may be a useful marker of the inflammatory disorder typical of some patients.
Molecular Genetics
Feldmann et al. (2002) identified heterozygous missense mutations in exon 3 of the CIAS1 gene (e.g., 606416.0007) in the affected members of each of 7 families with CINCA syndrome.
Of 3 patients with CINCA syndrome studied by Leone et al. (2003), only 1 had a mutation in exon 3 of the CIAS1 gene.
Aksentijevich et al. (2002) identified heterozygous missense mutations in exon 3 of the CIAS1 gene in 6 of 13 patients with CINCA syndrome. No mutation in the CIAS1 gene was found in the other 7 patients, suggesting genetic heterogeneity. Aksentijevich et al. (2002) found no discernible differences in the clinical features of patients with or without mutations in CIAS1.
Clinical Management
Boschan et al. (2006) reported a 5-year-old boy with a CIAS1 mutation and symptoms of severe systemic inflammation suggestive of NOMID. Although prior antiinflammatory therapy had only limited success, treatment with the IL1R antagonist (IL1RN; 147679) anakinra led to remarkable improvement of the clinical and laboratory findings. There was disappearance of rash, cessation of fever episodes with abdominal pain and vomiting, reduction in hepatosplenomegaly and lymph node size, progressive closure of the anterior fontanel, and reduction in papilledema. Serologically, white blood cell count, C-reactive protein (123260) and amyloid A (104750) levels, and erythrocyte sedimentation rate all normalized. The patient became more agile and outgoing and made large developmental advances within a short period of time.
REFERENCES
Aksentijevich, I., Nowak, M., Mallah, M., Chae, J. J., Watford, W. T., Hofmann, S. R., Stein, L., Russo, R., Goldsmith, D., Dent, P., Rosenberg, H. F., Austin, F., and 19 others. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum. 46: 3340-3348, 2002. [PubMed: 12483741, images, related citations] [Full Text]
Boschan, C., Witt, O., Lohse, P., Foeldvari, I., Zappel, H., Schweigerer, L. Neonatal-onset multisystem inflammatory disease (NOMID) due to a novel S331R mutation of the CIAS1 gene and response to interleukin-1 receptor antagonist treatment. Am. J. Med. Genet. 140A: 883-886, 2006. [PubMed: 16532456, related citations] [Full Text]
Feldmann, J., Prieur, A.-M., Quartier, P., Berquin, P., Certain, S., Cortis, E., Teillac-Hamel, D., Fischer, A., de Saint Basile, G. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am. J. Hum. Genet. 71: 198-203, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 1258 only, 2002. [PubMed: 12032915, images, related citations] [Full Text]
Hassink, S. G., Goldsmith, D. P. Neonatal onset multisystem inflammatory disease. Arthritis Rheum. 26: 668-673, 1983. [PubMed: 6847730, related citations] [Full Text]
Leone, V., Presani, G., Perticarari, S., Tommasini, A., Crovella, S., Lenhardt, A., Picco, P., Lepore, L. Chronic infantile neurological cutaneous articular syndrome: CD10 over-expression in neutrophils is a possible key to the pathogenesis of the disease. Europ. J. Pediat. 162: 669-673, 2003. [PubMed: 12928894, related citations] [Full Text]
Prieur, A. M., Griscelli, C. Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation. J. Pediat. 99: 79-83, 1981. [PubMed: 7252669, related citations] [Full Text]
Prieur, A. M. A recently recognised chronic inflammatory disease of early onset characterised by the triad of rash, central nervous system involvement and arthropathy. Clin. Exp. Rheum. 19: 103-106, 2001. [PubMed: 11247311, related citations]
Prieur, A.-M., Griscelli, C., Lampert, F., Truckenbrodt, H., Guggenheim, M. A., Lovell, D. J., Pelkonnen, P., Chevrant-Breton, J., Ansell, B. M. A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome: a specific entity analysed in 30 patients. Scand. J. Rheum. Suppl. 66: 57-68, 1987.
Torbiak, R. P., Dent, P. B., Cockshott, W. P. NOMID–a neonatal syndrome of multisystem inflammation. Skeletal Radiol. 18: 359-364, 1989. [PubMed: 2781338, related citations]
Borrowed from: https://www.omim.org/entry/607115
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