Homozygous IL1RN Mutation in Siblings with Deficiency of Interleukin-1 Receptor Antagonist (DIRA)
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LETTER TO EDITOR
Homozygous IL1RN Mutation in Siblings with Deficiency of Interleukin-1 Receptor Antagonist (DIRA) Vahid Ziaee 1,2 & Leila Youssefian 3,4,5,6 & Masoomeh Faghankhani 3,6 & Ali Jazayeri 7 & Amir Hossein Saeidian 3,4,6 & Hassan Vahidnezhad 3,6,8 & Jouni Uitto 3,6 Received: 14 August 2019 / Accepted: 24 February 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
To the Editor: Deficiency of the interleukin 1 (IL-1) receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory syndrome caused by loss-of-function mutations in the IL1RN gene which result in the synthesis of nonfunctional interleukin-1 receptor antagonist (IL1RA), leading to uninhibited attachment of IL-1β to its receptor [1, 2]. The IL-1βtriggered signaling pathway activates MAP kinase and NF-κB, causing expression of pro-inflammatory cytokines, chemokines, and secondary mediators of inflammation [3, 4]. DIRA, mostly diagnosed at birth or within the early neonatal period, presents with three cardinal manifestations: (a) sterile pustular, erythematous, and scaly skin lesions, (b) sterile multifocal osteomyelitis, and (c) periostitis [1]. Up to now, 17 affected families have been reported (Table 1) [1, 2, 5–13].
Case Presentation The proband was a 16-year-old male of Iranian-Persian ancestry born to double first-cousin healthy parents (Fig. 1a; III-2). He presented from the age of 1.5 months
with recurrent episodes of fever and mucositis. His manifestations progressed to pustular rash, erythematous, and scaling skin, which however, lessened with advancing age (Fig. 1b). He had several hospital admissions due to a pathologic fracture of the right wrist, sterile osteomyelitis, arthritis, pneumonia, or cytomegalovirus-associated enteritis. He also demonstrated nail dystrophy, chronic fatigue, paleness, developmental and growth retardation, and his height and weight were below the 5th percentile. He had difficulty in ambulation due to debilitating chronic musculoskeletal pain, epiphyseal overgrowth of knees, and peripheral joint contractures without axial joint involvement. He was initially diagnosed as psoriatic arthritis, and he was under treatment with non-biologic diseasemodifying anti-rheumatic drugs (DMARDs) with poor response. The proband’s younger female sibling was born with similar cutaneous and skeletal manifestations, triangular facies, and protruding ears, along with mild cardiomegaly and more severe respiratory problems including respiratory distress and recurrent pneumonia leading to yearly multiple hospital admissions since age one; she died at 3 years of age (Fig. 1b; Patient III-3).
Vahid Ziaee, Leila Youssefian and Masoomeh Faghankhani contributed equally to this work. * Hassan Vahidnezhad [email protected]
4
Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, USA
* Jouni Uitto [email protected]
5
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
1
Pediatric R
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