Majeed syndrome L98.3; M86.-

Majeed et al. 1989

Majeed syndrome is a rare inflammatory, autosomal recessive multisystem human disease associated with chronic multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia (CDA) with or without neutrophilic dermatosis (Sweet syndrome).

MJDS is extraordinarily rare. So far, only 24 individuals from 10 families with genetically confirmed Majeed syndrome have been described in the literature

MJDS is associated with mutations in the LPIN2 gene, which is located on chromosome 18p11.31 and codes for the phosphatidic acid phosphatase LIPIN2. Data to date indicate that a disruption of phosphatidic acid phosphatase activity in LIPIN2 leads to immune system dysregulation due to abnormal activation of the NLRP3 inflammasome and overproduction of proinflammatory cytokines, including IL-1beta.

Early onset with 1 to 3 inflammatory, sometimes febrile episodes per month . Further failure to thrive, height and weight were below the 5th percentile in the first-described family, and bone age was delayed. All affected individuals had significant hepatosplenomegaly. Blood transfusions were required on several occasions. Inconstant occurrence of Sweet syndrome as well as severe pustular psoriasis (Ferguson et al. 2005). The clinical course in the first-described family was similar in all 3 children; the unaffected parents in both families were related by blood.

Signs of inflammation; in peripheral blood smears: frequent hypochromia and microcytosis.

There is evidence that pharmacologic blockade of the interleukin-1 pathway is associated with rapid clinical improvement (Ferguson PJ et al. 2021).

1. Ferguson PJ et al (2005) Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia (Majeed syndrome). J Med Genet 42: 551-557.
2. Ferguson PJ et al (2021) Majeed syndrome: A Review of the Clinical, Genetic and Immunologic Features. Biomolecules 28;11(3):367.
3. Majeed HA et al. (2001) The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia: report of a new family and a review. Europ. J. Pediat. 160: 705-710.
4. Majeed HA et al. (2000) On mice and men: an autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia. (Letter) J Pediat 137: 441-442.
5. Majeed HA et al (1989) Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. J Pediat 115: 730-734.