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Chronic infantile neurological, cutaneous and articular syndrome(CINCA)

MedGen UID:
98370
Concept ID:
C0409818
Disease or Syndrome
Synonyms: Chronic Infantile Neurological Cutaneous Articular syndrome; CHRONIC NEUROLOGIC CUTANEOUS AND ARTICULAR SYNDROME; CINCA; CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME 3; Infantile Onset Multisystem Inflammatory Disease; Neonatal Onset Multisystem Inflammatory Disease; Prieur Griscelli syndrome
SNOMED CT: NOMID - Neonatal onset multisystem inflammatory disease (239826001); Neonatal onset multisystem inflammatory disease (239826001); Chronic infantile neurological, cutaneous and articular syndrome (239826001); CINCA - Chronic infantile neurological, cutaneous and articular syndrome (239826001)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): NLRP3 (1q44)
 
Monarch Initiative: MONDO:0011776
OMIM®: 607115
Orphanet: ORPHA1451

Definition

Chronic infantile neurologic cutaneous and articular syndrome (CINCA) is an early-onset, severe, chronic inflammatory disease, 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. [from OMIM]

Additional description

From MedlinePlus Genetics
Individuals with MWS develop the typical periodic episodes of skin rash, fever, and joint pain after cold exposure, although episodes may occur spontaneously or all the time. Additionally, they can develop progressive hearing loss in their teenage years. Other features of MWS include skin lesions or kidney damage from abnormal deposits of a protein called amyloid (amyloidosis).

In people with NOMID, the signs and symptoms of the condition are usually present from birth and persists throughout life. In addition to skin rash and fever, affected individuals may have joint inflammation, swelling, and joint deformities called contractures that may restrict movement. People with NOMID typically have headaches, seizures, and cognitive impairment resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Other features of NOMID include eye problems, short stature, distinctive facial features, and kidney damage caused by amyloidosis.

While the CAPS spectrum shares similar signs and symptoms, the individual conditions tend to have distinct patterns of features. People with FCAS1 are particularly sensitive to the cold, and exposure to cold temperatures can trigger a painful or burning rash. The rash usually affects the torso and limbs but may spread to the rest of the body. In addition to fever and joint pain, other possible symptoms include muscle aches, chills, drowsiness, eye redness, headache, and nausea.

The signs and symptoms of CAPS affect multiple body systems. Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain. These episodes can be triggered by exposure to cold temperatures, fatigue, other stressors, or they may arise spontaneously. Episodes can last from a few hours to several days. These episodes typically begin in infancy or early childhood and persist throughout life.

Cryopyrin-associated periodic syndromes (CAPS) are a group of conditions that have overlapping signs and symptoms and the same genetic cause. The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. FCAS1 is the least severe form of CAPS, MWS is intermediate in severity, and NOMID is the most severe form.  https://medlineplus.gov/genetics/condition/cryopyrin-associated-periodic-syndromes

Clinical features

From HPO
Patellar overgrowth
MedGen UID:
1782823
Concept ID:
C5539503
Anatomical Abnormality
Excessive growth of the kneecap (patella).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Progressive sensorineural hearing impairment
MedGen UID:
335894
Concept ID:
C1843156
Disease or Syndrome
A progressive form of sensorineural hearing impairment.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Increased count of eosinophils in the blood.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Meningitis
MedGen UID:
6298
Concept ID:
C0025289
Disease or Syndrome
Inflammation of the meninges.
Uveitis
MedGen UID:
52961
Concept ID:
C0042164
Disease or Syndrome
Inflammation of one or all portions of the uveal tract.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Optic papillitis
MedGen UID:
10565
Concept ID:
C0030353
Finding
Papilledema refers to edema (swelling) of the optic disc secondary to any factor which increases cerebral spinal fluid pressure.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVChronic infantile neurological, cutaneous and articular syndrome
Follow this link to review classifications for Chronic infantile neurological, cutaneous and articular syndrome in Orphanet.

Professional guidelines

PubMed

Koné-Paut I, Galeotti C
Expert Rev Clin Immunol 2015;11(10):1083-92. Epub 2015 Aug 27 doi: 10.1586/1744666X.2015.1077702. PMID: 26312542
Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A
J Clin Immunol 2008 May;28 Suppl 1:S73-83. Epub 2008 Mar 27 doi: 10.1007/s10875-008-9178-3. PMID: 18368292

Recent clinical studies

Etiology

Marzano AV, Tavecchio S, Venturini M, Sala R, Calzavara-Pinton P, Gattorno M
G Ital Dermatol Venereol 2015 Feb;150(1):41-50. Epub 2015 Jan 14 PMID: 25586657
Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A
J Clin Immunol 2008 May;28 Suppl 1:S73-83. Epub 2008 Mar 27 doi: 10.1007/s10875-008-9178-3. PMID: 18368292
Rynne M, Maclean C, Bybee A, McDermott MF, Emery P
Ann Rheum Dis 2006 Apr;65(4):533-4. doi: 10.1136/ard.2005.038091. PMID: 16531551Free PMC Article
Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C, Shoham N, Aganna E, Hugot JP, Wise C, Waterham H, Pugnere D, Demaille J, Sarrauste de Menthiere C
Hum Mutat 2004 Sep;24(3):194-8. doi: 10.1002/humu.20080. PMID: 15300846

Diagnosis

Luo XY, Chen AW, Cai JH, Fang J, Wang H
J Dermatol 2020 Aug;47(8):903-906. Epub 2020 Jun 3 doi: 10.1111/1346-8138.15414. PMID: 32490544
Marzano AV, Tavecchio S, Venturini M, Sala R, Calzavara-Pinton P, Gattorno M
G Ital Dermatol Venereol 2015 Feb;150(1):41-50. Epub 2015 Jan 14 PMID: 25586657
Montealegre Sanchez GA, Hashkes PJ
Dev Med Child Neurol 2009 Jun;51(6):420-8. doi: 10.1111/j.1469-8749.2009.03336.x. PMID: 19563585
Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A
J Clin Immunol 2008 May;28 Suppl 1:S73-83. Epub 2008 Mar 27 doi: 10.1007/s10875-008-9178-3. PMID: 18368292
Russo RA, Katsicas MM
Acta Paediatr 2001 Sep;90(9):1076-9. doi: 10.1080/080352501316978192. PMID: 11683199

Therapy

Koné-Paut I, Galeotti C
Expert Rev Clin Immunol 2015;11(10):1083-92. Epub 2015 Aug 27 doi: 10.1586/1744666X.2015.1077702. PMID: 26312542
Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, Stricker K, Chakraborty A, Tannenbaum S, Wright AM, Rordorf C
Arthritis Res Ther 2011 Feb 28;13(1):R34. doi: 10.1186/ar3266. PMID: 21356079Free PMC Article
Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A
J Clin Immunol 2008 May;28 Suppl 1:S73-83. Epub 2008 Mar 27 doi: 10.1007/s10875-008-9178-3. PMID: 18368292
Kawashima H, Sato A, Nishimata S, Yamada N, Kashiwagi Y, Watanabe K, Takekuma K, Hoshika A, Ozawa T
Ther Apher Dial 2007 Jun;11(3):232-4. doi: 10.1111/j.1744-9987.2007.00465.x. PMID: 17498007
Russo RA, Katsicas MM
Acta Paediatr 2001 Sep;90(9):1076-9. doi: 10.1080/080352501316978192. PMID: 11683199

Prognosis

Kim BJ, Kim YH, Han JH, Lee SY, Carandang M, Lee DH, Lee S, Choi BY
Otol Neurotol 2021 Feb 1;42(2):e168-e171. doi: 10.1097/MAO.0000000000002933. PMID: 33156237
Kawashima H, Sato A, Nishimata S, Yamada N, Kashiwagi Y, Watanabe K, Takekuma K, Hoshika A, Ozawa T
Ther Apher Dial 2007 Jun;11(3):232-4. doi: 10.1111/j.1744-9987.2007.00465.x. PMID: 17498007

Clinical prediction guides

Kim BJ, Kim YH, Han JH, Lee SY, Carandang M, Lee DH, Lee S, Choi BY
Otol Neurotol 2021 Feb 1;42(2):e168-e171. doi: 10.1097/MAO.0000000000002933. PMID: 33156237
Hentgen V, Despert V, Leprêtre AC, Cuisset L, Chevrant-Breton J, Jégo P, Chalès G, Gall EL, Delpech M, Grateau G
J Rheumatol 2005 Apr;32(4):747-51. PMID: 15801036
Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint Basile G
Am J Hum Genet 2002 Jul;71(1):198-203. Epub 2002 May 24 doi: 10.1086/341357. PMID: 12032915Free PMC Article
Russo RA, Katsicas MM
Acta Paediatr 2001 Sep;90(9):1076-9. doi: 10.1080/080352501316978192. PMID: 11683199

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