Majeed Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Majeed syndrome is characterized by:

1. Chronic recurrent multifocal osteomyelitis (CRMO) that is of early onset with a lifelong course; and

2. Congenital dyserythropoietic anemia (CDA) that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion dependent.

Some individuals also develop a transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration).

Diagnosis/testing: The diagnosis is based on clinical findings and molecular genetic testing of LPIN2, the only gene in which pathogenic variants are known to cause Majeed syndrome.

Management: Treatment of manifestations: CRMO is treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy to avoid disuse atrophy of muscles and contractures. If CRMO does not respond to NSAIDs, corticosteroids can be used short term to control CRMO and skin manifestations; however, the complications of long-term use of corticosteroids limit their use in children. Two affected children had resolution of their bone inflammation when treated with an IL-1 inhibitor. Physical therapy should be employed to avoid disuse atrophy of muscles or contractures. CDA is treated with red blood cell transfusion if indicated.

Surveillance: Routine complete blood count (CBC) to determine if red blood cell transfusion is necessary.

Agents/circumstances to avoid: Prolonged bed rest.

Genetic counseling: Majeed syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives is possible if the pathogenic variants in the family are known. If the pathogenic variants in the family have been identified, prenatal testing for pregnancies at increased risk is possible through laboratories offering either testing for the gene of interest or custom testing.