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Familial cold autoinflammatory syndrome 2(FCAS2)

MedGen UID:: 435869
•Concept ID:: C2673198
•: Disease or Syndrome

Synonym:	FCAS2
SNOMED CT:	NLR family pyrin domain containing 12-associated hereditary periodic fever syndrome (783146009); FCAS2 - familial cold autoinflammatory syndrome type 2 (783146009); NLRP12-associated hereditary periodic fever syndrome (783146009); Familial cold autoinflammatory syndrome type 2 (783146009)
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. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	NLRP12 (19q13.42)

Monarch Initiative:	MONDO:0012724
OMIM®:	611762
Orphanet:	ORPHA247868

Definition

Familial cold autoinflammatory syndrome-2 (FCAS2) is an autosomal dominant autoinflammatory disorder characterized by episodic and recurrent rash, urticaria, arthralgia, myalgia, and headache. In most patients, these episodes are accompanied by fever and serologic evidence of inflammation. Most, but not all, patients report exposure to cold as a trigger for the episodes. Additional features may include abdominal pain, thoracic pain, and sensorineural deafness. The age at onset is variable, ranging from the first year of life to middle age, and the severity and clinical manifestations are heterogeneous (summary by Shen et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of familial cold autoinflammatory syndrome, see FCAS1 (120100). [from OMIM]

Additional description

From MedlinePlus Genetics
Familial cold autoinflammatory syndrome type 2 is a condition that causes episodes of fever, skin rash, and joint pain. These episodes can be triggered by exposure to cold temperatures, or they may arise without warning, and they can last a few hours to several days. These episodes typically begin in childhood and persist throughout life.

Episodes typically occur after an hour or more of cold exposure in affected individuals who are sensitive to cold; however only a few minutes of cold exposure is required in some individuals.

In people with familial cold autoinflammatory syndrome type 2, the most common symptom that occurs during an episode is a fever. Other common features are an itchy rash and joint and muscle pain.

Additional features of familial cold autoinflammatory syndrome type 2 include abdominal pain, diarrhea, headache, and nausea. Some affected individuals develop hearing loss (sensorineural deafness) due to chronic inflammation. https://medlineplus.gov/genetics/condition/familial-cold-autoinflammatory-syndrome-type-2

Clinical features

From HPO

Abdominal pain

MedGen UID:: 7803
•Concept ID:: C0000737
•: Sign or Symptom

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

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Arthralgia

MedGen UID:: 13917
•Concept ID:: C0003862
•: Sign or Symptom

Joint pain.

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Lower limb pain

MedGen UID:: 6033
•Concept ID:: C0023222
•: Sign or Symptom

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the leg.

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Myalgia

MedGen UID:: 68541
•Concept ID:: C0231528
•: Sign or Symptom

Pain in muscle.

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Sensorineural hearing loss disorder

MedGen UID:: 9164
•Concept ID:: C0018784
•: Disease or Syndrome

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

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Headache

MedGen UID:: 9149
•Concept ID:: C0018681
•: Sign or Symptom

Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.

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Arthritis

MedGen UID:: 2043
•Concept ID:: C0003864
•: Disease or Syndrome

Inflammation of a joint.

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Pharyngalgia

MedGen UID:: 116585
•Concept ID:: C0242429
•: Sign or Symptom

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the throat.

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Erythema nodosum

MedGen UID:: 41858
•Concept ID:: C0014743
•: Disease or Syndrome

An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral.

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Leukocytosis

MedGen UID:: 9736
•Concept ID:: C0023518
•: Disease or Syndrome

An abnormal increase in the number of leukocytes in the blood.

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Splenomegaly

MedGen UID:: 52469
•Concept ID:: C0038002
•: Finding

Abnormal increased size of the spleen.

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Lymphadenopathy

MedGen UID:: 96929
•Concept ID:: C0497156
•: Disease or Syndrome

Enlargment (swelling) of a lymph node.

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Skin rash

MedGen UID:: 1830322
•Concept ID:: C5779628
•: Sign or Symptom

A red eruption of the skin.

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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.

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Recurrent fever

MedGen UID:: 811468
•Concept ID:: C3714772
•: Sign or Symptom

Periodic (episodic or recurrent) bouts of fever.

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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.

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Recurrent aphthous stomatitis

MedGen UID:: 445425
•Concept ID:: C2937365
•: Disease or Syndrome

Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.

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Urticaria

MedGen UID:: 22587
•Concept ID:: C0042109
•: Disease or Syndrome

Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.

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Show all Hide all

Abnormality of head or neck
- Recurrent aphthous stomatitis
Abnormality of metabolism/homeostasis
Abnormality of the immune system
Abnormality of the integument
- Urticaria
Abnormality of the musculoskeletal system
- Arthritis
Abnormality of the nervous system
- Headache
Abnormality of the respiratory system
- Pharyngalgia
Constitutional symptom
Ear malformation
- Sensorineural hearing loss disorder

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVFamilial cold autoinflammatory syndrome
- CROGVFamilial cold autoinflammatory syndrome 1
- CROGVFamilial cold autoinflammatory syndrome 2
- CROGVFamilial cold autoinflammatory syndrome 3
- CROGVFamilial cold autoinflammatory syndrome 4

Autoinflammatory syndrome with skin involvement
- Familial cold autoinflammatory syndrome 2

Follow this link to review classifications for Familial cold autoinflammatory syndrome 2 in Orphanet.

Recent clinical studies

Etiology

NLRP12-associated systemic autoinflammatory diseases in children.

Wang HF
Pediatr Rheumatol Online J 2022 Feb 5;20(1):9. doi: 10.1186/s12969-022-00669-8. PMID: 35123508 Free PMC Article

See all (1)

Diagnosis

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

Demir F, Sözeri B
Clin Exp Rheumatol 2023 Oct;41(10):2115-2121. Epub 2023 Oct 9 doi: 10.55563/clinexprheumatol/kzggp3. PMID: 37877365

NLRP12-associated systemic autoinflammatory diseases in children.

Wang HF
Pediatr Rheumatol Online J 2022 Feb 5;20(1):9. doi: 10.1186/s12969-022-00669-8. PMID: 35123508 Free PMC Article

Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases.

Davis MDP, van der Hilst JCH
J Allergy Clin Immunol Pract 2018 Jul-Aug;6(4):1162-1170. Epub 2018 Jun 2 doi: 10.1016/j.jaip.2018.05.006. PMID: 29871797

See all (3)

Therapy

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

Demir F, Sözeri B
Clin Exp Rheumatol 2023 Oct;41(10):2115-2121. Epub 2023 Oct 9 doi: 10.55563/clinexprheumatol/kzggp3. PMID: 37877365

See all (1)

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Familial cold autoinflammatory syndrome 2(FCAS2)

Definition

Additional description

Clinical features

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Therapy

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