Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

Sarrabay, Guillaume; Grandemange, Sylvie; Touitou, Isabelle

doi:10.1586/1744666x.2015.1047765

Cited by 28 publications

(21 citation statements)

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“…Finally, in one case (ISO87), a class 3 variant was identified in NLRP3, a gene known to underlie autosomal dominant cryporin-associated periodic syndromes, for example, Muckle-Wells syndrome. 18 Further clinical evaluation in the patient revealed, however, no evidence for this syndrome and the variant was therefore considered not to be the cause of the HI.…”

Section: Diagnostic Yield With Wes In Hi Patientsmentioning

confidence: 88%

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

et al. 2016

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Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes. Two hundred index patients, mostly of Dutch origin, with presumed hereditary HI underwent WES followed by targeted analysis of an HI gene panel of 120 genes. We found causative variants underlying the HI in 67 of 200 patients (33.5%). Eight of these patients have a large homozygous deletion involving STRC, OTOA or USH2A, which could only be identified by copy number variation detection. Variants of uncertain significance were found in 10 patients (5.0%). In the remaining 123 cases, no potentially causative variants were detected (61.5%). In our patient cohort, causative variants in GJB2, USH2A, MYO15A and STRC, and in MYO6 were the leading causes for autosomal recessive and dominant HI, respectively. Segregation analysis and functional analyses of variants of uncertain significance will probably further increase the diagnostic yield of WES.

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Section: Diagnostic Yield With Wes In Hi Patientsmentioning

confidence: 88%

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

et al. 2016

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“…As already stated, up to 35–40% of patients with a clear CINCA/NOMID phenotype turn out to be negative for germ-line mutations of NLRP3 [17]. Almost 70% of these patients are, instead, carriers of a somatic mosaicism [44], that can involve even a very low percentage of the cells of myeloid lineage [17]. There is a general consensus among experts that the clinical picture of CINCA/NOMID is sufficient to point out the diagnosis even in the absence of a positive genetic test [45].…”

Section: Diagnosis and Diagnostic Methodsmentioning

confidence: 99%

Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review

Finetti

Omenetti

Federici

et al. 2016

Orphanet J Rare Dis

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IntroductionThe Chronic Infantile Neurological Cutaneous and Articular (CINCA, or Neonatal-onset multisystem inflammatory disease NOMID) is a rare autoinflammatory disease identified in 1987 by Prieur et al., typically characterized by the triad of skin rash, arthropathy and central nervous system manifestations. It represents the most severe phenotype of the cryopyrin-associated periodic syndrome (CAPS).Clinical description and etiologyThe syndrome is due to autosomal dominant gain of function mutations in NLRP3, which encodes a key component of the innate immunity that regulates the activation and secretion of interleukin (IL)-1β. From the first days of life, patients display an urticarial rash in association with chronic inflammation with a typical facies featured by frontal bossing and saddle back nose. The CNS manifestations include chronic aseptic meningitis leading to brain atrophy, mental delay and sensorineural hearing loss. Chronic polyarthritis and alteration of the growth cartilage also may be present. CINCA/NOMID diagnosis is made clinically, based on the presence of characteristic features. The detection of NLRP3 mutations is diagnostic in 65–70% of cases. Indeed, up to 40% of affected patients are negative for germline NLRP3 mutations and several subjects are carriers of somatic mosaicism. Due to the pivotal role of Cryopyrin in the control of Caspase-1 activation and the massive secretion of active IL-1β observed in cryopyrin-mutated individuals, anti-IL1 treatment represents the standard therapy.ConclusionPrognosis of CINCA/NOMID syndrome has been changed by the availability of anti-IL1 drugs. Nowadays, the use of anti-IL-1 drugs has sensibly reduced the risk of developing main complications such as severe intellectual disability, hearing-loss and amyloidosis, if treatment is started early on.

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“…Gout progresses in four stages: isolated hyperuricemia, crystal deposition, acute flares and advanced gout with tophi, chronic gouty arthritis and erosions (41)(42)(43). Monosodium urate is the acute trigger of the NLRP3 inflammasome in acute gouty flares, recruiting caspase-1 which activates IL-1β (15,42,45,46). Acute gout is characterized by articular and periarticular inflammation with excruciating pain that commonly resolves after one or two weeks and typically involves the first metatarsophalangeal joints and, more rarely, ankles, knees, midfoot, wrists, elbow and bursae; fever can be present, particularly in polyarticular cases (41,43).…”

Section: N Polygenic Aidsmentioning

confidence: 99%

“…Acute CPP crystal arthritis is treated with intraarticular steroids (often as first-line option), oral colchicine, NSAIDs and/or systemic steroids; IL-1 inhibitors have also been successful (48,50). Schnitzler's syndrome is a late-onset AID that invariably presents with both monoclonal gammopathy and chronic urticarial rash (11,46,51,52). These features are often accompanied by fever, bone pain, arthritis, lymphadenopathy, hepatomeg-aly and/or splenomegaly, and leukocytosis (52).…”

Section: N Polygenic Aidsmentioning

confidence: 99%

Adult-onset systemic autoinflammatory disorders: a clinical approach

2020

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Autoinflammatory disorders (AIDs) are a subgroup of immune-mediated syndromes that result from a primary dysfunction of the innate immune system. AIDs can be either monogenic or polygenic diseases. Unlike organspecific AIDs, systemic AIDs are characterized by fever and/or elevation of acute-phase reactants. This review aims to describe the most common adult-onset systemic AIDs, focusing mostly on polygenic and mixed-pattern diseases which are expected to be more prevalent in adult patients than monogenic AIDs overall. The literature was searched in Medline database. Organ-specific or childhood-onset systemic AIDs were excluded. AIDs were divided in three distinct groups: mixed-pattern, polygenic and adult-onset monogenic AIDs. Most adult-onset AIDs are polygenic but late-onset disease is not rare among monogenic AIDs such as familial Mediterranean fever (FMF). The diagnosis of systemic AIDs in adults is often delayed due to several factors and sometimes it is only established when amyloidosis or other complications are present. Therefore, it probably makes sense to primarily exclude common AIDs in adult patients with fever of unknown origin (and probably different presentations such as polyserositis) since a high prevalence of adult-onset Still’s disease or FMF is usually expected. Colchicine, nonsteroidal anti-inflammatory drugs, steroids, immunosuppressive agents, interleukin-1 inhibitors and tumor necrosis factor antagonists constitute common therapeutic options for systemic AIDs.

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Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

Cited by 28 publications

References 71 publications

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review

Adult-onset systemic autoinflammatory disorders: a clinical approach

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