Phenotype–Genotype Analysis of Cryopyrin-Associated Periodic Syndromes (CAPS): Description of a Rare Non-Exon 3 and a Novel CIAS1 Missense Mutation

Abstract

We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

Pediatric hereditary autoinflammatory syndromes

“…A FCAS (OMIM n o 120100), também chamada de urticária familiar ao frio, situa-se no extremo benigno das criopirinopatias, possuindo o melhor prognóstico do grupo 6,61,71 . A doença é caracterizada por surtos de febre baixa (93%), poliartralgia (96%) e rash urticariforme não pruriginoso (100%) que surge de 1 a 2 horas após exposição ao frio (variando de 30 minutos a 6 horas), e dura cerca de 12 horas 7,71,72 .…”

“…A doença é caracterizada por surtos de febre baixa (93%), poliartralgia (96%) e rash urticariforme não pruriginoso (100%) que surge de 1 a 2 horas após exposição ao frio (variando de 30 minutos a 6 horas), e dura cerca de 12 horas 7,71,72 . Outros sintomas comumente relatados são: conjuntivite (84%), sudorese profusa (78%), tonturas (67%), cefaleia (58%), náuseas (51%) e sede excessiva (53%) 72 .…”

“…A maioria dos doentes apresenta epifisite e metafisite de ossos longos, determinando calcificação epifiseal anormal e crescimento excessivo da cartilagem, com consequente encurtamento dos membros e deformidades articulares. Ossificação patelar prematura com crescimento excessivo patelar simétrico é um achado característico da doença 69,71,84 . Artropatia típica é vista em 50% dos pacientes 69 .…”

Síndromes autoinflamatórias hereditárias na faixa etária pediátrica

“…6,10 The signs and symptoms presented in Tables 2 and 3 proper recognition of these conditions is essential for individualized treatment. 43,71,128,129 …”

“…Premature ossification of the patella, with symmetrical patellar overgrowth, is a characteristic finding. 69,71,84 The typical arthropathy of NOMID is found in 50% of patients. 69 Nonspecific laboratory changes are as in other autoinflammatory syndromes, and may include anemia, thrombocytosis, moderately increased white blood cell counts, and increased inflammatory markers, such as ESR and CRP levels.…”