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Familial amyloid nephropathy with urticaria AND deafness(MWS)

MedGen UID:
120634
Concept ID:
C0268390
Disease or Syndrome
Synonyms: CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME 2; MUCKLE-WELLS SYNDROME; MWS; UDA syndrome; Urticaria, deafness and amyloidosis; Urticaria-deafness-amyloidosis syndrome
SNOMED CT: Familial amyloid nephropathy with urticaria AND deafness (15123008); Muckle-Wells syndrome (15123008); Muckle-Wells type amyloidosis (15123008); Amyloid nephropathy with deafness and urticaria (15123008)
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.
 
Gene (location): NLRP3 (1q44)
 
Monarch Initiative: MONDO:0008633
OMIM®: 191900
Orphanet: ORPHA575

Definition

Muckle-Wells syndrome (MWS) is characterized by episodic skin rash, arthralgias, and fever associated with late-onset sensorineural deafness and renal amyloidosis (Dode et al., 2002). [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.

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).  https://medlineplus.gov/genetics/condition/cryopyrin-associated-periodic-syndromes

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Chronic fatigue
MedGen UID:
760077
Concept ID:
C0518656
Finding
Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer.
Renal amyloidosis
MedGen UID:
120633
Concept ID:
C0268382
Disease or Syndrome
A form of amyloidosis that affects the kidney. On hematoxylin and eosin stain, amyloid is identified as extracellular amorphous material that is lightly eosinophilic. These deposits often stain weakly for periodic acid Schiff (PAS), demonstrate a blue-to-gray hue on the trichrome stain and are typically negative on the Jones methenamine silver (JMS) stain. These tinctorial properties contrast with the histologic appearance of collagen, a major component of basement membranes, mesangial matrix and areas of sclerosis, which demonstrates strong positivity for PAS and JMS (See Figure 1 of PMID:25852856).
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Vasculitis
MedGen UID:
12054
Concept ID:
C0042384
Disease or Syndrome
Inflammation of blood vessel.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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.
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.
Increased intracranial pressure
MedGen UID:
56241
Concept ID:
C0151740
Finding
An increase of the pressure inside the cranium (skull) and thereby in the brain tissue and cerebrospinal fluid.
Polyarticular arthritis
MedGen UID:
56408
Concept ID:
C0162323
Disease or Syndrome
Pain and inflammation in more than five joints.
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Maculopapular exanthema
MedGen UID:
98072
Concept ID:
C0423791
Finding
A skin rash that is characterized by diffuse cutaneous erythema with areas of skin elevation. It may evolve to vesicles or papules as part of a more severe clinical entity. Different degrees of angioedema with involvement of subcutaneous tissue may also appear.
Deep dermal perivascular inflammatory infiltrate
MedGen UID:
1611554
Concept ID:
C4531289
Finding
Numerous lymphocytes surrounding blood vessels in the deep part of the dermis.
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.
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.
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.
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.
Conjunctival hyperemia
MedGen UID:
315653
Concept ID:
C1761613
Finding
Dilatation of the blood vessels of the conjunctiva leading to a red appearance of the sclera.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial amyloid nephropathy with urticaria AND deafness
Follow this link to review classifications for Familial amyloid nephropathy with urticaria AND deafness in Orphanet.

Professional guidelines

PubMed

Marzano AV, Maronese CA, Genovese G, Ferrucci S, Moltrasio C, Asero R, Cugno M
J Allergy Clin Immunol 2022 Apr;149(4):1137-1149. doi: 10.1016/j.jaci.2022.02.007. PMID: 35396080
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA
Nat Med 2015 Mar;21(3):248-55. Epub 2015 Feb 16 doi: 10.1038/nm.3806. PMID: 25686105Free PMC Article

Recent clinical studies

Etiology

Kagami S, Saeki H, Kuwano Y, Imakado S, Tamaki K
J Dermatol 2006 Feb;33(2):118-21. doi: 10.1111/j.1346-8138.2006.00025.x. PMID: 16556280

Diagnosis

Kagami S, Saeki H, Kuwano Y, Imakado S, Tamaki K
J Dermatol 2006 Feb;33(2):118-21. doi: 10.1111/j.1346-8138.2006.00025.x. PMID: 16556280

Prognosis

Kagami S, Saeki H, Kuwano Y, Imakado S, Tamaki K
J Dermatol 2006 Feb;33(2):118-21. doi: 10.1111/j.1346-8138.2006.00025.x. PMID: 16556280

Clinical prediction guides

Kagami S, Saeki H, Kuwano Y, Imakado S, Tamaki K
J Dermatol 2006 Feb;33(2):118-21. doi: 10.1111/j.1346-8138.2006.00025.x. PMID: 16556280
Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA, Scott DG, Nicholls A, Pavek S, Vasseur C, Beckmann JS, Delpech M, Grateau G
Am J Hum Genet 1999 Oct;65(4):1054-9. doi: 10.1086/302589. PMID: 10486324Free PMC Article

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