Majeed Syndrome

Majeed syndrome is a very rare condition characterized by recurrent episodes of fever and inflammation in the bones and skin. This condition has two main features: 1) chronic recurrent multifocal osteomyelitis (CRMO) and 2) congenital dyserythropoietic anemia (CDA).

This condition causes recurrent episodes of pain and joint swelling beginning in infancy or early childhood and the symptoms persist into adulthood. CRMO can lead to complications such as slow growth and the development of joint deformities called contractures, which restrict the movement of certain joints.

CDA is one of many types of anemia, all of which involve a shortage of red blood cells. Without enough of these cells, the blood cannot carry an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and shortness of breath. Complications of congenital dyserythropoietic anemia can range from mild to severe.

Most people with Majeed syndrome also develop inflammatory disorders of the skin, most often a condition known as Sweet syndrome. The symptoms of Sweet syndrome include fever and the development of painful bumps or blisters on the face, neck, back, and arms.

Clinical features develop in early childhood, no later than 2 years of age. The youngest reported onset has been at 3 weeks of age.

 

Genetics

Majeed syndrome is caused by mutations in the LPIN2 gene. This gene provides instructions for making a protein called lipin-2. Researchers believe that this protein may play a role in the processing of fats (lipid metabolism). However, no lipid abnormalities have been found with Majeed syndrome. Lipin-2 also may be involved in controlling inflammation and in cell division.

Mutations in the LPIN2 gene alter the structure and function of lipin-2. It is unclear how these genetic changes lead to bone disease, anemia, and inflammation of the skin in people with Majeed syndrome.

This condition is inherited in an autosomal recessive pattern, which means that two copies of the mutated gene are required, one from each carrier parent. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Although carriers typically do not show signs and symptoms of the condition, some parents of children with Majeed syndrome have had an inflammatory skin disorder called psoriasis.

 

Epidemiology

Only a small number of families have so far been identified with Majeed syndrome, and all have come from the Middle East. The rate of carriage of the mutations in Arab populations would predict this syndrome should be seen more commonly. It has therefore been suggested that it is under-diagnosed.

 

 

Clinical features

The clinical features are acute episodes of fever, pain and joint swelling that last several days, with 1-3 flares per month.

 

Treatment

The use of biological agents such as anakinra or canakinumab in the treatment of Majeed syndrome demonstrates clinical improvement with IL-1 blockade. This is supported by recent evidence of the role of lipin-2 in the inflammasome and highlights the key role of IL-1 signalling in Majeed syndrome.

 

References:

Mosawi, Zakiya Al et al. “Dramatic Response of Familial Majeed Syndrome to Interleukin-1 Antagonist Therapy: Case report.” Archives of rheumatology, Volume 34 – Issue 3 (September 2019): Pages 352-356 . https://doi.org/10.5606/ArchRheumatol.2019.7267

Akhila Kavirayani, Sarah Sacks, Noemi Roy, Ruth Finch, Elaine Parsons, Nick Wilkinson, 023. Autoinflammatory bone disease: Majeed syndrome- description of a novel mutation and therapeutic response to Bisphosphonates and IL-1 blockade, Rheumatology, Volume 56, Issue suppl_6, October 2017, kex356.007, https://doi.org/10.1093/rheumatology/kex356.007

Noémi B A Roy, Ahmad I Zaal, Georgina Hall, Nick Wilkinson, Melanie Proven, Simon McGowan, Ria Hipkiss, Veronica Buckle, Akhila Kavirayani, Christian Babbs, Majeed syndrome: description of a novel mutation and therapeutic response to bisphosphonates and IL-1 blockade with anakinra. Rheumatology, kez317, Published: 04 August 2019 https://doi.org/10.1093/rheumatology/kez317

Herlin, Troels & Fiirgaard, Bente & Bjerre, Mette & Kerndrup, Gitte & Hasle, Henrik & Bing, Xinyu & Ferguson, Polly. (2012). Efficacy of anti-IL-1 treatment in Majeed syndrome. Annals of the rheumatic diseases. 72 (3), October 2012. http://dx.doi.org/10.1136/annrheumdis-2012-201818

Arch Rheumatol. 2019 Jun; 34(3): 352–356. 10.5606/ArchRheumatol.2019.7267

Therapy: Case report Majeed Syndrome https://dermnetnz.org/topics/majeed-syndrome

Majeed Syndrome https://ghr.nlm.nih.gov/condition/majeed-syndrome

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