Showing papers on "Majeed syndrome published in 2019"

Majeed syndrome: description of a novel mutation and therapeutic response to bisphosphonates and IL-1 blockade with anakinra

Abstract: cupying lesions, myositis and sub-cutaneous oedema and can therefore lead to diagnostic uncertainty. Biopsy is commonly considered the gold standard for identification of muscle pathology but is in fact an undesirable procedure in this condition, due to poor wound healing in the affected population. Treatment is largely conservative, and includes analgesia, physiotherapy to prevent muscle contractures and optimization of glycaemic control [2]. Immunosuppression, for inflammatory muscle disease, is not warranted, and indeed steroids would be ill-advised in a patient who already has a complication of poor glycaemic control. Several pathogenic mechanisms have been postulated in DMI including microangiopathic disease, artherosclerotic occlusion and thrombosis leading to muscle infarct. Furthermore initial muscle injury may be perpetuated by a cycle of hypoxia reperfusion injury and an inflammatory response leading to muscle oedema and compartment syndrome [3].

Compound heterozygous LPIN2 pathogenic variants in a patient with Majeed syndrome with recurrent fever and severe neutropenia: case report.

Abstract: Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome. We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2. Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.

Dramatic Response of Familial Majeed Syndrome to Interleukin-1 Antagonist Therapy: Case report.

Abstract: Majeed syndrome (MS) is a rare, autosomal recessive, autoinflammatory disease characterized by recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and inflammatory dermatome. In this article, we report the cases of two siblings with MS. Genetic studies of both siblings were obtained and revealed mutations in LPIN2 gene by means of a homozygous single-base pair change in the donor splice site of exon 17 (c.2327+1G>C). Both patients underwent different modalities of treatment for MS which involved immune-suppressive and biologic therapies. We observed a significant clinical response to biologic anti-interleukin-1 (IL-1) therapy in our patients. This impressive clinical response indicates the pivotal role of IL-1 in MS pathogenesis. There are limited data on the use of anti-IL-1 therapy in treating MS due to the rarity of the condition. Anti-IL-1 therapy should be considered as a promising treatment for this disease.

Genetic Causes of Inflammatory Bone Disease

Abstract: 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.

Imaging of Chronic Recurrent Multifocal Osteomyelitis and Autoinflammatory Bone Disorders

Abstract: Autoinflammatory bone diseases are disorders characterized by chronic osteitis, bone resorption, and abnormal remodeling resulting from aberrant unprovoked activation of the innate immune system The areas affected by chronic bone inflammation are typically culture-negative, with no apparent pathogen on histopathology Inflammatory skin lesions are often present, as well as accompanying fever Chronic recurrent multifocal osteomyelitis (CRMO), SAPHO syndrome, Majeed syndrome, pyoderma gangrenosum and acne (PAPA), deficiency of interleukin-1 receptor antagonist (DIRA), CINCA/NOMID, and cherubism are among the most common autoinflammatory bone disorders in childhood, and CRMO is by far the most studied and well-recognized of them all This chapter covers the imaging findings of some of these diseases, focusing on CRMO as the prototypical condition of the group