Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency

Pediatr Dev Pathol. 2017 Jun;20(3):255-261. doi: 10.1177/1093526616686255. Epub 2017 Jan 27.

Abstract

Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity. We report here a case of multifocal Bacillus Calmette-Guérin osteomyelitis in a context Mendelian susceptibility to mycobacterial disease mimicking a metastatic neuroblastoma in a child presenting with delayed growth. The investigation of her twin sister showed the same disease. A heterozygous mutation in exon 22 of STAT1 gene was found in both sisters, another sister and the father being healthy and heterozygous for the same mutation.

Keywords: Bacillus Calmette-Guérin; Mendelian susceptibility to mycobaterial disease; STAT1; osteomyelitis; primary immunodeficiency.

Publication types

  • Case Reports

MeSH terms

  • Diseases in Twins / diagnosis
  • Diseases in Twins / genetics*
  • Female
  • Genetic Diseases, Inborn / complications
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Infant
  • Mutation
  • Mycobacterium Infections / diagnosis
  • Mycobacterium Infections / genetics*
  • Mycobacterium bovis / isolation & purification*
  • Osteomyelitis / diagnosis
  • Osteomyelitis / genetics*
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics*

Substances

  • Genetic Markers
  • STAT1 Transcription Factor
  • STAT1 protein, human