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Disease Profile

Neonatal Onset Multisystem Inflammatory disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

E85.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Chronic Infantile Neurological Cutaneous Articular syndrome; CINCA syndrome; CINCA;

Categories

Congenital and Genetic Diseases; Eye diseases; Immune System Diseases;

Summary

Neonatal onset multisystem inflammatory disease (NOMID) is an inflammatory disorder present from birth (congenital) characterized by tissue damage of the nervous system, skin, and joints. Individuals with NOMID have a skin rash that is present from birth and persists throughout life. Other symptoms may include: headaches, seizures, and vomiting resulting from chronic meningitis (inflammation of the tissue that covers and protects the brain and spinal cord); intellectual disability; episodes of mild fever; and hearing and vision problems.[1][2] NOMID is the most severe form of the cryopyrin associated periodic syndromes (CAPS) caused by mutations in the NLRP3 (CIAS1) gene. About 50% of affected individuals with NOMID are found to have mutations in this gene. This condition is inherited in an autosomal dominant manner.[3][2] Treatment may include the use of medications to suppress the process of inflammation, such as anti-inflammatories, corticosteroids, and interleukin-1 beta receptors.[3][4]

Symptoms

The symptoms of neonatal onset multisystem inflammatory disease (NOMID) start at birth, or are observed within the first weeks of life. The first symptoms are usually a skin rash and fever. Individuals with NOMID may also have chronic meningitis (inflammation of the membranes surrounding the brain), which may lead to headaches, seizures, and vomiting. Hearing loss, vision loss, and intellectual disability, may also occur.

People with NOMID often 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, including a prominent forehead and protruding eyes. There is an increased risk for individuals with NOMID to develop abnormal deposits of a protein called amyloid (amyloidosis), which may cause kidney damage.[2][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of neutrophils
0001874
Arthralgia
Joint pain
0002829
Brachydactyly
Short fingers or toes
0001156
Elevated C-reactive protein level
0011227
Elevated erythrocyte sedimentation rate
High ESR
0003565
Fatigue
Tired
Tiredness

[ more ]

0012378
Fever
0001945
Increased intracranial pressure
Rise in pressure inside skull
0002516
Meningitis
0001287
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Nausea and vomiting
0002017
Papule
0200034
Pseudopapilledema
0000538
Sensorineural hearing impairment
0000407
Urticaria
Hives
0001025
Uveitis
0000554
30%-79% of people have these symptoms
Abnormal thrombocyte morphology
Platelet abnormalities
0001872
Anemia
Low number of red blood cells or hemoglobin
0001903
Delayed closure of the anterior fontanelle
Later than typical closing of soft spot of skull
0001476
Edema
Fluid retention
Water retention

[ more ]

0000969
Frontal bossing
0002007
Hepatomegaly
Enlarged liver
0002240
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Leukocytosis
Elevated white blood count
High white blood count
Increased blood leukocyte number

[ more ]

0001974
Lymphadenopathy
Swollen lymph nodes
0002716
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Skeletal dysplasia
0002652
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Blindness
0000618
EEG abnormality
0002353
Global developmental delay
0001263
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Purpura
Red or purple spots on the skin
0000979
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Retrobulbar optic neuritis
0100654
1%-4% of people have these symptoms
Arthritis
Joint inflammation
0001369
Childhood onset
Symptoms begin in childhood
0011463
Eosinophilia
High blood eosinophil count
0001880
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Neonatal onset
0003623
Papilledema
0001085
Progressive sensorineural hearing impairment
0000408
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever

[ more ]

0001954
Seizure
0001250
Skin rash
0000988
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006

Cause

Neonatal onset multisystem inflammatory disease (NOMID) is a genetic disease, often caused by mutations in the NLRP3 (also known as CIAS1) gene. In almost all cases, NOMID results from new mutations within this gene. These cases occur in people with no history of the disorder in their family (de novo). A few cases have been reported in which an affected person has inherited the mutation from one affected parent. In these instances, the disorder is inherited in an autosomal dominant manner.[2]

The NLRP3 gene provides instructions for making a protein called cryopyrin. Cryopyrin is found mainly in white blood cells and in cartilage-forming cells (chondrocytes) and plays a role in the immune system, helping to start and regulate the immune system response. It is suspected that mutations within the NLRP3 gene cause cryopyrin to be overactive, leading to an inappropriate inflammatory response that results the symptoms of in NOMID.[2] 

A genetic mutation in the NLRP3 gene is not found in about 50% of individuals with NOMID.[2][4]

Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

    • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • Genetics Home Reference (GHR) contains information on Neonatal Onset Multisystem Inflammatory disease. This website is maintained by the National Library of Medicine.
      • The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. Click on the link to view information on this topic.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Neonatal Onset Multisystem Inflammatory disease. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Victor A. McKusick. CINCA Syndrome. In: Marla J. F. O'Neill. Online Mendelian Inheritance in Man (OMIM). 2/13/2012; https://www.omim.org/entry/607115. Accessed 10/25/2016.
            2. neonatal onset multisystem inflammatory disease. Genetics Home Reference. September 2008; https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease#definition. Accessed 10/25/2016.
            3. Hoffman H. Neonatal-onset Multisystem Inflammatory Disease. National Organization for Rare Disorders (NORD). 2011; https://rarediseases.org/rare-diseases/neonatal-onset-multisystem-inflammatory-disease/. Accessed 10/25/2016.
            4. NOMID/CINCA. Autoinflammatory Alliance. https://www.autoinflammatory.org/nomid.php. Accessed 10/25/2016.

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