CINCA Syndrome With New NLRP3 Mutation and Unreported Complication of Thyroid Carcinoma.

BACKGROUND: Chronic infantile neurologic cutaneous and articular syndrome (CINCA) is the most severe phenotype of cryopyrin-associated periodic syndromes (CAPS) and is caused by a missense mutation in NLRP3 gene. CASE PRESENTATION: We are reporting a 15-year-old male patient with complaints of chronic arthritis and mental involvement. Further investigations showed a heterozygous c.785G>A missense mutation in Exon 3 of NLRP3 gene and coexisting medullary thyroid carcinoma 2 years later. CONCLUSIONS: This case showed a recently identified gene variant of NLRP3 in a CINCA patient, as a heterozygous c.785G>A missense mutation in Exon 3 of NLRP3 gene and coexisted medullary thyroid carcinoma as an unreported complication of CINCA.

Selective rickets from localized advanced maturation-a case report.

An unusual cause of rickets is illustrated by a patient with infantile multisystem inflammatory disease who, by age 2 years and 4 months, developed striking radiographic and clinical rickets restricted to those joints involved by the inflammatory process. The locally increased vascularity from his inflammation led to increased maturation at those sites so rapid as to override the usual enchondral calcification, thus causing a rickets pattern. Other sites, such as the proximal humeri, lacking any inflammation, showed no increased maturation rate and did not manifest local rickets. Rapid local bone maturation may cause localized rickets.

Analyses of gene mutation, clinical phenotype, treatment and follow up of 10 cases with chronic infantile neurologic, cutaneous, articular syndrome / 中华风湿病学杂志

Objective To explore the gene mutation,clinical phenotype,treatment and prognosis of chronic infantile neurologic,cutaneous,articular (CINCA) syndrome,so as to improve the diagnosis rate,reduce the disability rate and teratogenicity rate of CINCA syndrome.Methods Ten children with CINCA syndrome admitted to our hospital were retrospectively analyzed in terms of the clinical phenotypes,auxiliary examinations,treatment and follow-up.Three ml ethylene diamine tetraacetic acid (EDTA) anticoagul-ation was taken from children and their parents with the consents.Genomic DNA was extracted by QIAamp whole blood Deoxynbonucleic acid (DNA) extraction kit (German Qiagen Company).The whole exons were detected by Agilent liquid phase capture technology (Agilent Company).Finally,Sanger sequencing was used to verify the results.Results In this study,eight mutations of NLRP3 gene were found in children with CINCA syndrome,namely 913G/A (D305N),1057G/T(V353L),1702T/A (F568I),1703T/A (F568Y),1710G/C (K570N),1789A/G (S597G),1991T/C (M664T),2269G/A (G757R).The onset age of most of the cases was less than half a month,and the initial manifestation was mainly urticaria-like rash.Short stature and special face could be seen in all 10 cases.All the patients had fever and urticarial rash in varying degrees during the course of the disease.Nine of them had obvious arthritis.Nine children had central nervous system involvement.There were 8 cases of binaural nervous deafness,7 cases of binocular optic neuritis,and 6 cases of hepato-splenomegaly and/or lymphadenopathy.Amyloid A was significantly increased.Glucocorticoids and immunosup-pressive agents are the basic drugs for the treatment of this disease.If the curative effect was not good,biological agents should be added early to alleviate the disease.Conclusion CINCA syndrome is a rare autosomal dominant hereditary disease,the main clinical manifestations of which are skin,joint and central nervous system involvement,and even amyloidosis of organs.Early diagnosis and active treatment can reduce the involvement of important organs.

Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare autoinflammatory disorder driven by uncontrolled hypersecretion of interleukin (IL)-1, which can be clinically depicted by striking cutaneous, neurologic, and skeletal features. Little is known about the exact pathogenesis of CINCA bone disease, which mainly involves the knees. We report a 20-year-old CINCA patient, who was consecutively treated firstly with anakinra, started at 7 years, then with full dose canakinumab, started at 17 years, focusing on the typical bone abnormalities of the syndrome: the comparison of radiographs of knees performed at 7 and 20 years has shown the disappearance of a typical metaphyseal dysplasia occurring in the femurs of this CINCA patient, regularly treated with IL-1 blockade for a period of 13 years. A review of the medical literature reveals poor information on the skeletal response of CINCA syndrome to IL-1-inhibiting therapies. This contribution confirms the protean striking effects of IL-1 blockade in this peculiar autoinflammatory disorder, showing for the first time the reversal of the characteristic CINCA metaphyseal dysplasia over long-term treatment.

Dental Treatment in a Patient with CINCA Syndrome under General Anesthesia / 대한소아치과학회지

Chronic infantile neurological cutaneous articular (CINCA) syndrome periodically causes fever along with inflammation in multiple organs. Patients with this condition are vulnerable to dental problems due to systemic inflammation. For uncooperative patients, general anesthesia has been widely used to control negative behavior. However, caution should be exercised when administering general anesthesia in these patients because this syndrome is pro-inflammatory. The present case report describes the clinical considerations of the dental treatment of an uncooperative child with CINCA syndrome who was treated under general anesthesia.

CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report.

Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a systemic autoinflammatory disease caused by increased production of interleukin (IL)-1ß. We present a case of CINCA syndrome followed up to skeletal maturity. Joint contracture and valgus deformity of the knee had developed before diagnosis. Surgical interventions by soft tissue release and hemiepiphysiodesis improved the contracture and the deformity, and IL-1 receptor antagonist dramatically controlled systemic inflammation, and the patient lives without any disabilities.

Síndrome CINCA: um diagnóstico diferencial da artrite idiopática juvenil / CINCA syndrome: a differential diagnosis of the juvenile idiopathic arthritis

A síndrome CINCA (crônico-infantil-neurológica-cutâneaarticular) é uma enfermidade inflamatória multissistêmica rara, de início no período neonatal e caracterizada por febre, exantema cutâneo, envolvimento articular e do sistema nervoso central. É também conhecida pela literatura médica norte-americana como NOMID (doença multissistêmica inflamatória de início neonatal). Relatamos o caso de uma criança de 3 anos de idade admitida em nosso serviço com história de febre e exantema cutâneo desde o período neonatal. Apresentou crises convulsivas no sexto mês de vida e artrite simétrica de joelhos desde o nono mês. Na admissão, mostrava-se toxemiada, pálida, com um exantema maculopapular generalizado e artrite de joelhos e tornozelos. Apresentava ainda retardo de crescimento e desenvolvimento. Achados laboratoriais incluíram anemia, leucocitose, trombocitose, níveis elevados de proteína C reativa e meningite asséptica no exame do liquor. Os outros exames foram negativos. Os achados radiográficos dos joelhos, quadris e tornozelos foram anormais. A criança recebeu tratamento com antiinflamatório não hormonal, corticosteróide e metotrexato, com melhora apenas da dor e da febre. A etiologia da síndrome CINCA permanece desconhecida e nenhum tratamento tem se mostrado eficaz. Essa doença deve ser distinguida da forma sistêmica da artrite idiopática juvenil (AIJ), o principal diagnóstico diferencial.

CINCA syndrome (chronic-infantile-neurological-cutaneousarticular) is a rare multisystemic inflammatory disease with neonatal onset characterized by fever, skin rash, articular, and central nervous system involvement. This syndrome is known in the North American medical literature as infantile onset multisystem inflammatory disease (NOMID). We describe the case of a 3-yearold child admitted in our service with fever and skin rash since the neonatal period. She presented seizures at 6 months-old and bilateral arthritis of the knees since her 9 months. On admission she looked sick, pale and presented generalized erythematosus maculopapular rash, arthritis of the knees and ankles. She presented growth and mental retardation too. Laboratory Endings included anemia, leukocytosis, thrombocytosis, elevated C-reactive protein levels and the examination Endings from the cerebrospinal fluid showed an aseptic meningitis. Other test results were negative. Radiographs of the knees, hips and ankles revealed abonrmalities. The child received treatment with nonsteroidal anti-inflammatory drugs, corticosteroids and methotrexate, with partial response to treatment, leading to improvement in pain and fever defervescence. The etiology of CINCA syndrome remains unknown and no single treatment has been found to be effective. This disease should be distinguished from systemic onset juvenile idiophatic arthritis (JIA), the main differential diagnosis.