Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report

Pediatr Rheumatol Online J. 2022 Apr 11;20(1):24. doi: 10.1186/s12969-022-00686-7.


Background: Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation.

Case presentation: We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/β receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved.

Conclusions: JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight.

Keywords: Auto inflammation; Autoimmunity; Janus kinase inhibitor; Ruxolitinib; Singleton Merten syndrome; Therapy; Type I interferon.

Publication types

  • Case Reports

MeSH terms

  • Aortic Diseases
  • Child
  • Child, Preschool
  • Dental Enamel Hypoplasia
  • Humans
  • Interferon Type I*
  • Interferon-Induced Helicase, IFIH1 / genetics
  • Male
  • Metacarpus / abnormalities
  • Muscle Weakness
  • Muscular Diseases
  • Nitriles
  • Odontodysplasia
  • Osteoporosis* / genetics
  • Pyrazoles
  • Pyrimidines
  • Vascular Calcification


  • Interferon Type I
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Interferon-Induced Helicase, IFIH1

Supplementary concepts

  • Singleton Merten syndrome