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

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 STAT1 primary immunodeficiency osteomyelitis Mendelian susceptibility to mycobaterial disease

Get full access to this article

View all access options for this article.

References

Bustamante

Boisson-Dupuis

Abel

Casanova

. Mendelian susceptibility to mycobacterial disease: genetic, immunological and clinical features of inborn errors of INF-γ immnunity. Semin Immunol 2014; 26(6): 454–470.

Gimenez Sanchez

Cobos-Carrascosa

Sanchez-Forte

. Different penetrance of disseminated infections caused by nontuberculous mycobacteria in Mandelian susceptibility to mycobacetrial disease associated with a novel mutation. Pediatr Infect Dis J 2014; 33(3): 328–330.

Casanova

Abel

. Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 2002; 20: 581–620.

Jouanguy

Lamhamedi-Cherradi

Lammas

. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 1999; 21(4): 370–378.

Dorman

Picard

Lammas

. Clinical features of dominant and recessive interferon γ receptor 1 deficiencies. Lancet 2004; 364(9451): 2113–2121.

Boisson-Dupuis

Kong

Okada

. Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes. Curr Opin Immunol 2012; 24(4): 364–378.

Dupuis

Dargemont

Fieschi

. Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science 2001; 293(5528): 300–302.

Hirata

Okada

Tsumura

. Heterozygosity for the Y701C STAT1 mutation in a multiplex kindred with multifocal osteomyelitis. Haematologica 2013; 98(10): 1641–1649.

Edgar

Smyth

Pritchard

. Interferon-γ receptor deficiency mimicking Langerhans’cell histiocytosis. J Pediatr 2001; 139(4): 600–603.

10.

Emile

Patey

Altare

. Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection. J Pathol 1997; 181(1): 25–30.