Genetic Causes of Inflammatory Bone Disease

  • James Verbsky
  • Polly J. FergusonEmail author


This chapter focuses on monogenic autoinflammatory disorders that affect bone. The presence of sterile bone inflammation may be accompanied by inflammation of the skin and intestinal tract. The pathophysiology varies by syndrome and includes dysregulation of the IL-1 pathway or aberrant intracellular signaling defects leading to activation of innate immune cells including osteoclasts. These are rare disorders with variable outcomes. IL-1 inhibitors have been used successfully to decrease inflammation in Majeed syndrome, deficiency of the interleukin receptor antagonist and for non-osseous manifestations of neonatal onset multisystem inflammatory disease. For other disorders such as cherubism, treatment remains challenging. Recognition of additional monogenic autoinflammatory is likely as this is a very new field of investigation.


Majeed syndrome Deficiency of the interleukin-1 receptor antagonist (DIRA) Interleukin-1 Neonatal onset multisystem inflammatory disease (NOMID) Cherubism Schnitzler syndrome Primary hypertrophic osteoarthropathy LPIN2 NLRP3 Pstpip2 SH3BP2 



Adenosine diphosphate


Apoptosis-associated speck-like protein containing a carboxy-terminal CARD


Abelson murine leukemia viral oncogene homolog 1


Congenital dyserythropoietic anemia (CDA)


Chronic non-bacterial osteomyelitis


Chronic recurrent multifocal osteomyelitis


C-reactive protein


C-terminal Src kinase


Deficiency of the interleukin-1 receptor antagonist


Extracellular signal-regulated kinase


Erythrocyte sedimentation rate


Filamin binding LIM protein 1 gene


Filamin binding LIM protein 1


15-hydroxyprostaglandin dehydrogenase




IL-1 receptor accessory protein


IL-1 receptor I


Interleukin-1 receptor antagonist gene symbol


Interleukin 1 receptor associated kinase 4


Lipin2 gene symbol


MAP kinase


Macrophage colony-stimulating factor


Magnetic resonance imaging


Myeloid differentiation primary response 88


Nuclear factor of activated T-cells


NLR family pyrin domain containing 3


Neonatal onset multisystem inflammatory disease


Nuclear receptor subfamily 4 group A member 2


Non-steroidal anti-inflammatory drugs


Purinergic receptor P2X 7


Phosphatidate phosphatase


Primary hypertrophic osteoarthropathy


Proline-serine-threonine phosphatase interacting protein 2


 Protein-tyrosine phosphatase with proline (P), glutamic acid (E), serine (S), and threonine (T) motif


Receptor activator of nuclear factor kappa-Β ligand


SH3 binding protein 2


Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1


Signal transducer and activator of transcription


Short tau inversion recovery


Spleen tyrosine kinase


Tumor necrosis factor


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PediatricsMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of PediatricsUniversity of Iowa Carver College of MedicineIowa CityUSA

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