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Genetics Home Reference: your guide to understanding genetic conditions
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Neonatal onset multisystem inflammatory disease

(often shortened to NOMID)
Reviewed September 2008

What is NOMID?

Neonatal onset multisystem inflammatory disease (NOMID) is a disorder that causes persistent inflammation and tissue damage primarily affecting the nervous system, skin, and joints. Recurrent episodes of mild fever may also occur in this disorder.

People with NOMID have a skin rash that is usually present from birth. The rash persists throughout life, although it changes in size and location.

Affected individuals often have headaches, seizures, and vomiting resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Intellectual disability may occur in some people with this disorder. Hearing and vision problems may result from nerve damage and inflammation in various tissues of the eyes.

People with NOMID experience joint inflammation, swelling, and cartilage overgrowth, causing characteristic prominent knees and other skeletal abnormalities that worsen over time. Joint deformities called contractures may restrict the movement of certain joints.

Other features of this disorder include short stature with shortening of the lower legs and forearms, and characteristic facial features such as a prominent forehead and protruding eyes. Abnormal deposits of a protein called amyloid (amyloidosis) may cause progressive kidney damage.

How common is NOMID?

NOMID is a very rare disorder; approximately 100 affected individuals have been reported worldwide.

What genes are related to NOMID?

Mutations in the NLRP3 gene (also known as CIAS1) cause NOMID. The NLRP3 gene provides instructions for making a protein called cryopyrin.

Cryopyrin belongs to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.

Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. Researchers believe that NLRP3 mutations that cause NOMID result in a hyperactive cryopyrin protein and an inappropriate inflammatory response. Impairment of the body's mechanisms for controlling inflammation results in the episodes of fever and widespread inflammatory damage to the body's cells and tissues seen in NOMID.

In about 50 percent of individuals diagnosed with NOMID, no mutations in the NLRP3 gene have been identified. The cause of NOMID in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with neonatal onset multisystem inflammatory disease.

  • NLRP3

How do people inherit NOMID?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In almost all cases, NOMID results from new mutations. These cases occur in people with no history of the disorder in their family. A few cases have been reported in which an affected person has inherited the mutation from one affected parent.

Where can I find information about diagnosis or management of NOMID?

These resources address the diagnosis or management of NOMID and may include treatment providers.

  • Genetic Testing Registry: Chronic infantile neurological, cutaneous and articular syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0409818)

You might also find information on the diagnosis or management of NOMID in Educational resources (http://www.ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about NOMID?

You may find the following resources about NOMID helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for NOMID?

  • chronic infantile neurological, cutaneous and articular syndrome
  • chronic infantile neurologic, cutaneous, and articular syndrome
  • chronic neurologic, cutaneous, and articular syndrome
  • CINCA
  • CINCA syndrome
  • infantile onset multisystem inflammatory disease
  • IOMID syndrome
  • Prieur-Griscelli syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about NOMID?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding NOMID?

amyloid ; amyloidosis ; autosomal ; autosomal dominant ; cartilage ; cell ; chronic ; cutaneous ; disability ; domain ; fever ; gene ; immune system ; inflammation ; inherited ; injury ; joint ; joint inflammation ; kidney ; leucine ; meninges ; mutation ; neonatal ; nervous system ; neurologic ; neurological ; nucleotide ; protein ; short stature ; stature ; syndrome ; tissue ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Aksentijevich I, D Putnam C, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007 Apr;56(4):1273-85. (http://www.ncbi.nlm.nih.gov/pubmed/17393462?dopt=Abstract)
  • Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, Stein L, Russo R, Goldsmith D, Dent P, Rosenberg HF, Austin F, Remmers EF, Balow JE Jr, Rosenzweig S, Komarow H, Shoham NG, Wood G, Jones J, Mangra N, Carrero H, Adams BS, Moore TL, Schikler K, Hoffman H, Lovell DJ, Lipnick R, Barron K, O'Shea JJ, Kastner DL, Goldbach-Mansky R. 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. 2002 Dec;46(12):3340-8. (http://www.ncbi.nlm.nih.gov/pubmed/12483741?dopt=Abstract)
  • Caroli F, Pontillo A, D'Osualdo A, Travan L, Ceccherini I, Crovella S, Alessio M, Stabile A, Gattorno M, Tommasini A, Martini A, Lepore L. Clinical and genetic characterization of Italian patients affected by CINCA syndrome. Rheumatology (Oxford). 2007 Mar;46(3):473-8. Epub 2006 Aug 18. (http://www.ncbi.nlm.nih.gov/pubmed/16920754?dopt=Abstract)
  • Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008 Jan;4(1):34-42. doi: 10.1038/ncprheum0681. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18172447?dopt=Abstract)
  • OMIM: CINCA SYNDROME (http://omim.org/entry/607115)
  • Dollfus H, Häfner R, Hofmann HM, Russo RA, Denda L, Gonzales LD, DeCunto C, Premoli J, Melo-Gomez J, Jorge JP, Vesely R, Stubna M, Dufier JL, Prieur AM. Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease syndrome: ocular manifestations in a recently recognized chronic inflammatory disease of childhood. Arch Ophthalmol. 2000 Oct;118(10):1386-92. (http://www.ncbi.nlm.nih.gov/pubmed/11030821?dopt=Abstract)
  • Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol. 2008 Mar;144(3):392-402. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18347298?dopt=Abstract)
  • Feldmann J, Prieur AM, 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. 2002 Jul;71(1):198-203. Epub 2002 May 24. (http://www.ncbi.nlm.nih.gov/pubmed/12032915?dopt=Abstract)
  • Hill SC, Namde M, Dwyer A, Poznanski A, Canna S, Goldbach-Mansky R. Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA). Pediatr Radiol. 2007 Feb;37(2):145-52. Epub 2006 Nov 28. (http://www.ncbi.nlm.nih.gov/pubmed/17136361?dopt=Abstract)
  • Kanazawa N, Furukawa F. Autoinflammatory syndromes with a dermatological perspective. J Dermatol. 2007 Sep;34(9):601-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17727363?dopt=Abstract)
  • 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. Eur J Pediatr. 2003 Oct;162(10):669-73. Epub 2003 Aug 20. (http://www.ncbi.nlm.nih.gov/pubmed/12928894?dopt=Abstract)
  • Saito M, Fujisawa A, Nishikomori R, Kambe N, Nakata-Hizume M, Yoshimoto M, Ohmori K, Okafuji I, Yoshioka T, Kusunoki T, Miyachi Y, Heike T, Nakahata T. Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 2005 Nov;52(11):3579-85. (http://www.ncbi.nlm.nih.gov/pubmed/16255047?dopt=Abstract)
  • Stankovic K, Grateau G. Auto inflammatory syndromes: Diagnosis and treatment. Joint Bone Spine. 2007 Dec;74(6):544-50. Epub 2007 Sep 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17950649?dopt=Abstract)
  • Tunca M, Ozdogan H. Molecular and genetic characteristics of hereditary autoinflammatory diseases. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):77-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15720239?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2008
Published: December 22, 2014