Author: Professor Gilles Grateau
Address for correspondence:
Pr Gilles GRATEAU
Service de médecine interne
Hôtel-Dieu
1 Place du Parvis Notre-Dame
75181 PARIS CEDEX 4
FRANCE
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Name of the disease and its synonyms
Muckle–Wells syndrome
Urticaria–deafness amyloidosis
Excluded diseases
Familial urticaria
Familial deafness
Hereditary amyloidosis type AA
Diagnostic criteria
They are purely clinical, however genetic diagnosis is currently feasible.
Differential diagnosis
This is a large group of diseases, many of which be considered as a function
of the predominant clinical symptoms, which vary from one family to another,
but also from one patient to another within the same family.
Incidence
It is unknown.
Clinical description
The first manifestations of Muckle–Wells syndrome consist of non-pruritic
urticaria, starting during infancy, and sometimes debilitating because they
are almost permanent, accompanied by a low-grade fever. The other inflammatory
signs are mainly joint (arthralgias or arthritides) and/or ocular (conjunctivitis)
involvement.
These inflammatory signs are associated with neurosensory deafness that
starts during adolescence. The severity of the disease resides in the
inconstant occurrence of generalized amyloidosis type AA.
The autosomal dominant inheritance has variable intra- and interfamilial
expression.
Management including treatments
There is no treatment to prevent urticarial attacks. Hearing aids can correct
deafness to some extent.
Etiology
The gene responsible for Muckle–Wells syndrome was localized to chromosome
1q44 in 1999 and recently identified. The CIAS1 (cold-induced autoinflammatory
syndrome 1) gene is expressed in peripheral blood leukocytes and encodes a
protein "cryopyrin" whith the same N terminal domain than pyrin, protein associated
to Familial Mediterranean Fever. Mutations in the CIAS1 gene are responsible
for two other syndromes : familial cold autoinflammatory syndrome (FCAS)
and CINCA (Chronic Infantile Neurological Cutaneous and Articular) syndrome.
Biological methods of diagnosis
No biological sign specific to Muckle–Wells syndrome has been identified;
only moderate non-specific signs of inflammation during the course of inflammatory
attacks are known. Some biochemical analyses are useful to exclude certain
diseases that can be considered as a function of the clinical signs present.
Unresolved questions and comments
The existence of other clinical signs in some families suggests the possibility
of genetic heterogeneity.
References
Muckle TJ, Wells M. Urticaria, deafness, and amyloidosis: a new heredo-familial
syndrome. Q J Med, 1962, 31 :235-248.
Berthelot JM; Maugars Y; Robillard N; Pascal O; Stalder JF; David A; Prost
A. Am J Med Genet, 1994 53: 72-74.
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.
Genetic Linkage of the Muckle-Wells Syndrome to Chromosome 1q44. Am J Hum
Genet 1999; 65: 1054-9.
Hoffman HM, Wright FA, Broide DH, Wanderer AA, Kolodner RD. Identification
of a locus on chromosome 1q44 for familial cold urticaria. Am J Hum
Genet 2000.
Dode C, Le Du N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G, Meyrier
A, Watts RA, Scott DG, Nicholls A, Granel B, Frances C, Garcier F, Edery P,
Boulinguez S, Domergues JP, Delpech M, Grateau G. New mutations of CIAS1 that
are responsible for Muckle-Wells syndrome and familial cold urticaria: a
novel mutation underlies both syndromes. Am J Hum Genet. 2002;70:1498-506.
Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of
a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory
syndrome and Muckle-Wells syndrome. Nature Genet 2001; 29:301-5
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This paper should be referenced as such
Grateau G, Muckle–Wells syndrome; Orphanet encyclopedia, March 1999, last
update June 2003:
http://orphanet.infobiogen.fr/data/patho/GB/uk-MWS.html
Scientific editor: Professor Didier Lacombe
Date of creation: March 1999
Update: July 2002
: June
2003
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