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URL of this page: https://medlineplus.gov/genetics/condition/majeed-syndrome/

Majeed syndrome

Description

Majeed syndrome is a rare condition that is characterized by recurrent episodes of fever and inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, Majeed syndrome causes abnormal inflammation that can damage the body's tissues, particularly the bones and, less commonly, the skin. The signs and symptoms of Majeed syndrome typically appear in infancy or early childhood and can vary from person to person.

One of the major features of Majeed syndrome is an inflammatory bone condition known as chronic recurrent multifocal osteomyelitis (CRMO). This condition causes recurrent episodes of bone pain and joint swelling. These symptoms continue into adulthood, although they may improve for short periods. CRMO can lead to complications such as slow growth and the development of joint deformities called contractures, which restrict the movement of certain joints.

Another feature of Majeed syndrome is a blood disorder called congenital dyserythropoietic anemia. This disorder 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. This can cause tiredness (fatigue), weakness, pale skin, and shortness of breath. The complications of congenital dyserythropoietic anemia can range from mild to severe.

Some people with Majeed syndrome develop an inflammatory disorder of the skin 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.

Frequency

Majeed syndrome is rare; approximately 30 individuals with this condition have been reported in the literature.

Causes

Variants (also called mutations) in the LPIN2 gene cause Majeed syndrome. This gene provides instructions for making a protein called lipin-2.  Lipin-2 helps regulate the inflammatory response, the first step in the immune system's response to injury. Lipin-2 is also thought to play a role in bone remodeling, the process by which old bone is removed and replaced by new bone.

Variants in the LPIN2 gene alter the structure and function of lipin-2. Research into how these gene variants cause the specific signs and symptoms of Majeed syndrome is still ongoing. Changes in the lipin-2 protein cause people with Majeed syndrome to produce more molecules that promote inflammation. In addition, individuals with Majeed syndrome produce more osteoclasts, which are cells that break down bone tissue. In people with Majeed syndrome, the overly active immune response leads to chronic inflammation and fevers, while the increased production of osteoclasts leads to excessive bone inflammation and remodeling.  

Learn more about the gene associated with Majeed syndrome

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Chronic recurrent multifocal osteomyelitis 1, with congenital dyserythropoietic anemia, with or without neutrophilic dermatosis
  • Chronic recurrent multifocal osteomyelitis-congenital dyserythropoietic anemia-neutrophilic dermatosis syndrome
  • CRM01
  • MJDS

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Al-Mosawi ZS, Al-Saad KK, Ijadi-Maghsoodi R, El-Shanti HI, Ferguson PJ. A splice site mutation confirms the role of LPIN2 in Majeed syndrome. Arthritis Rheum. 2007 Mar;56(3):960-4. doi: 10.1002/art.22431. Citation on PubMed
  • Bhuyan F, de Jesus AA, Mitchell J, Leikina E, VanTries R, Herzog R, Onel KB, Oler A, Montealegre Sanchez GA, Johnson KA, Bichell L, Marrero B, De Castro LF, Huang Y, Calvo KR, Collins MT, Ganesan S, Chernomordik LV, Ferguson PJ, Goldbach-Mansky R. Novel Majeed Syndrome-Causing LPIN2 Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis. Arthritis Rheumatol. 2021 Jun;73(6):1021-1032. doi: 10.1002/art.41624. Epub 2021 May 9. Citation on PubMed
  • El-Shanti HI, Ferguson PJ. Chronic recurrent multifocal osteomyelitis: a concise review and genetic update. Clin Orthop Relat Res. 2007 Sep;462:11-9. doi: 10.1097/BLO.0b013e3180986d73. Citation on PubMed
  • Ferguson PJ, Chen S, Tayeh MK, Ochoa L, Leal SM, Pelet A, Munnich A, Lyonnet S, Majeed HA, El-Shanti H. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J Med Genet. 2005 Jul;42(7):551-7. doi: 10.1136/jmg.2005.030759. Citation on PubMed or Free article on PubMed Central
  • Ferguson PJ, El-Shanti H. Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features. Biomolecules. 2021 Feb 28;11(3):367. doi: 10.3390/biom11030367. Citation on PubMed
  • Ferguson PJ, El-Shanti HI. Autoinflammatory bone disorders. Curr Opin Rheumatol. 2007 Sep;19(5):492-8. doi: 10.1097/BOR.0b013e32825f5492. Citation on PubMed
  • Hetrick R, Oliver M. Pediatric autoinflammatory bone disorders-a mini review with special focus on pathogenesis and inborn errors of immunity. Front Pediatr. 2023 Jun 5;11:1169659. doi: 10.3389/fped.2023.1169659. eCollection 2023. Citation on PubMed
  • Majeed HA, Al-Tarawna M, El-Shanti H, Kamel B, Al-Khalaileh F. The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. Report of a new family and a review. Eur J Pediatr. 2001 Dec;160(12):705-10. doi: 10.1007/s004310100799. Citation on PubMed
  • Majeed HA, Kalaawi M, Mohanty D, Teebi AS, Tunjekar MF, al-Gharbawy F, Majeed SA, al-Gazzar AH. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. J Pediatr. 1989 Nov;115(5 Pt 1):730-4. doi: 10.1016/s0022-3476(89)80650-x. Citation on PubMed
  • Narayanan DL, Gogineni KS, Badiger VA. LPIN2-Related Majeed Syndrome. 2023 Mar 2. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK589480/ Citation on PubMed
  • Nigrovic PA, Lee PY, Hoffman HM. Monogenic autoinflammatory disorders: Conceptual overview, phenotype, and clinical approach. J Allergy Clin Immunol. 2020 Nov;146(5):925-937. doi: 10.1016/j.jaci.2020.08.017. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.