Muckle–Wells syndrome: clinical perspectives

Figures & data

Figure 1 The NLRP3 inflammasome.

Notes: This figure schematizes the signaling cascade from the triggering inflammatory event to the fever and inflammation attack. The inflammasome is constituted of a multimeric assembly of units including one sensor (NLRP3), two connecting proteins (ASC and cardinal), and one effector (ICE). The number of units is still elusive. Adapted from Best Pract Res Clin Rheumatol, 22(5), Touitou and Koné-Paut, Autoinflammatory diseases, 811–829, Copyright 2008, with permission from Elsevier.⁴
Abbreviations: ASC, apoptosis-associated Speck-like protein containing a CARD; CARD, caspase recruitment domain-containing protein; DAMPS, damage-associated molecular patterns; ICE, interconvertin enzyme; IL-1, interleukin-1; LRR, leucine-repeat rich; NFκB, nuclear factor; NOD, nucleotide-binding oligomerization domain; PAMPS, pathogen-associated molecular pattern molecules; PYD, pyrin domain; TLR, Toll-like receptor.

Table 1 NLRP3 mutations and their clinical phenotypes

Mutation	Prevalence	Phenotype
R260W	25%	Symptom onset after the age of 6 months (median >2 years) Positive family history Cold-triggered attacks 42% undergo a chronic course
T348M	15%	Early age at onset (before the age of 6 months, median <2 months) 85% undergo a chronic course Hearing loss (70%)
V198M	10%	Low penetrance Median age of onset, ~1.5 years Neurological involvement uncommon
A439V	10%	Median age of onset, 4 years Neurological involvement uncommon Positive family history
E311K	7%	Median age of onset, 2 years High rate of hearing loss Neurological involvement uncommon
Q703K	7%	Considered as a polymorphism (5% of healthy Caucasians) Median age of onset, ~6 years (rarely before 12 months) Very mild disease No arthritis or neurological involvement (with the exception of morning headache) No family history No deafness
Rare mutations or no mutation	25%	Severe disease Early age of onset (before 6 months of age) Severe neurological manifestations Severe musculoskeletal involvement Hearing loss Severe ophthalmological manifestations

Note: Data from Levy et al.⁹

TouitouIKoné-PautIAutoinflammatory diseasesBest Pract Res Clin Rheumatol200822581182919028365

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LevyRGérardLKuemmerle-DeschnerJfor PRINTO and Euro-feverPhenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever RegistryAnn Rheum Dis201574112043204925038238

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