title: Long-term clinical profile of children with the low-penetrance R92Q mutation of the TNFRSF1A gene.
abstract: OBJECTIVE
  To analyze the long-term impact of the R92Q mutation of TNFRSF1A in children with periodic fever, in comparison with children with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) with TNFRSF1A structural mutations and children with periodic fever of unknown origin fulfilling the criteria for periodic fever, aphthosis, pharyngitis, and adenitis syndrome (PFAPA).
  
  
  METHODS
  The extracellular region of TNFRSF1A was analyzed in 720 consecutive children with periodic fever, using denaturing high-performance liquid chromatography and DNA sequencing. Followup data on 11 pediatric patients with TNFRSF1A structural mutations (cysteine or T50M), 23 pediatric patients with an R92Q substitution, and 64 pediatric patients with PFAPA were collected during routine clinic visits. The 50-item Child Health Questionnaire was used to assess health-related quality of life (HRQOL).
  
  
  RESULTS
  The frequency of typical TRAPS-related clinical manifestations was significantly lower and the impact of the disease on HRQOL was significantly reduced in patients with the R92Q mutation compared with TRAPS patients carrying structural mutations of TNFRSF1A. Followup data on 11 TRAPS patients with TNFRSF1A structural mutations (mean followup 7.9 years), 16 patients with theR92Q substitution (mean followup 7.3 years), and 64 patients with PFAPA (mean followup 5.2 years) were available. Patients with R92Q mutations and patients with PFAPA displayed a higher rate of self-resolution or amelioration of the fever episodes than did TRAPS patients with structural mutations.
  
  
  CONCLUSIONS
  Although some cases may progress to a more chronic disease course, the majority of children with an R92Q mutation of the TNFRSFA1 gene show a milder disease course than that in children with TNFRSFA1 structural mutations and have a high rate of spontaneous resolution and amelioration of the recurrent fever episodes.
authors.affiliation: Istituto G. Gaslini, Genoa, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Pelagatti
authors.forename: A
authors.initials: A
authors.lastname: Meini
authors.forename: R
authors.initials: R
authors.lastname: Caorsi
authors.forename: M
authors.initials: M
authors.lastname: Cattalini
authors.forename: S
authors.initials: S
authors.lastname: Federici
authors.forename: F
authors.initials: F
authors.lastname: Zulian
authors.forename: G
authors.initials: G
authors.lastname: Calcagno
authors.forename: A
authors.initials: A
authors.lastname: Tommasini
authors.forename: G
authors.initials: G
authors.lastname: Bossi
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: F
authors.initials: F
authors.lastname: Caroli
authors.forename: A
authors.initials: A
authors.lastname: Plebani
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: A
authors.initials: A
authors.lastname: Martini
authors.forename: M
authors.initials: M
authors.lastname: Gattorno
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001691:Biological Therapy; D002648:Child; D002675:Child, Preschool; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005500:Follow-Up Studies; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008137:Longitudinal Studies; D008199:Lymphadenitis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010612:Pharyngitis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013256:Steroids