Familial Behçet‑like autoinflammatory disease‑3 (AIFBL3), caused by heterozygous mutation in the rela gene: a case report

Abstract

Introduction: The autoinflammatory features of Behçet’s disease (BD) and the role of innate immunity dysregulation have been highlighted and BD can be considered as the crossroad of autoinflammatory and autoimmune diseases. Objectives: We describe the case of a 9-year-old caucasic male, who presented at age 6 y with recurrent episodes of fever, oral ulcers and pain at the limbs, hands, wrists. At the physical examination the child showed functional limitation of flexion and extension movements of the wrists (left > right) and a bilateral mild joint stiffness of the shoulders. He showed a mild delay in the stages of psychomotor development, and a mild hypotrophy of the muscles of the lower limbs. Methods: The metabolic disease expert excluded metabolic diseases, based on the metabolic diagnostic investigations. Ultrasound documented knees joint effusion in the lateral supra-patellar seat with synovial membrane’s thickening and evident right knee synovial phlogosis, minimal on the left. A Whole body MRI, reported intra joint fluid effusion in external lateral seat and in sub patellar seat of the left knee. Intraspongious edema of the cuboid of the right foot. The eye examination with slit lamp was normal; HLA-B27, Anti-streptolysin O titer, pharyngeal swab and specific serologies for infectious diseases were negative. Fecal calprotectin was normal. Antinuclear antibodies (ANA) were positive 1:320 with a granular pattern. Results: The genetic study in NGS for autoinflammatory diseases revealed a heterozygous mutation, defined as VUS, of the RELA gene: c.1537C>G (p.Pro513Ala). Mutations of the RELA gene are associated with a familiar autoinflammatory disease Behçet’s disease (BD)-like type 3, with an autosomal dominant transmission. The Familial Behçet-like autoinflammatory disease-3 (AIFBL3), caused by heterozygous mutation in the RELA gene on chromosome 11q13, is characterized predominantly by chronic mucocutaneous ulceration. Conclusion: The patient did not yet fulfil the paediatric BD (PEDBD) nor ICBD criteria for the diagnosis of paediatric BD, however it is well described that BD is an evolutionary disease, and clinical manifestations may appear over the years (1-3). Monogenic BD-like conditions are increasingly recognized and to date have been found to predominantly involve loss-of-function variants in TNFAIP3. This case describes a child carrying the RELA gene mutation, with clinical symptoms evoking BD. The RELA gene mutations are conditions related to dysregulated NF-κB activation and need a strict follow-up and a prompt start of treatment, also in patients who do not fulfil the diagnostic criteria for BD.