Alternative titles; symbols
SNOMEDCT: 703540008; ICD10CM: M04.8; ORPHA: 77297;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 18p11.31 | Majeed syndrome | 609628 | 3 | LPIN2 | 605519 |
A number sign (#) is used with this entry because of evidence that Majeed syndrome (MJDS) is caused by homozygous mutation in the LPIN2 gene (605519) on chromosome 18p11.
Majeed syndrome (MJDS) is an autosomal recessive pediatric multisystem autoinflammatory disorder characterized by chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia; some patients may also develop neutrophilic dermatosis. Additional features may include fever, failure to thrive, and neutropenia. Laboratory studies show elevated inflammatory markers consistent with activation of the proinflammatory IL1 (147760) pathway (summary by Ferguson and El-Shanti, 2021).
Genetic Heterogeneity of Chronic Recurrent Multifocal Osteomyelitis
See also CRMO2 (612852), caused by mutation in the IL1RN gene (147679) on chromosome 2q14; and CRMO3 (259680), caused by mutation in the IL1R1 gene (147810) on chromosome 2q12.
Majeed et al. (1989) reported 2 brothers and a female cousin who had chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia (CDA); the brothers also had neutrophilic dermatosis or Sweet syndrome. The clinical course of all 3 children was similar; the unaffected parents in both families were consanguineous.
Majeed et al. (2000) reported a fourth child with CRMO and CDA born into the consanguineous Arab family previously reported by Majeed et al. (1989), a brother of the female cousin. Over a period of 9 to 16 years of follow-up, the course of CRMO in these patients was characterized by early onset and 1 to 3 episodes per month, sometimes associated with mild fever. The 4 children failed to thrive; height and weight were below the 5th percentile with delayed bone age. All had significant hepatosplenomegaly and had required blood transfusions on several occasions. Their peripheral blood smears showed hypochromia and microcytosis, in contrast to the normo- and macrocytosis reported in other variants of CDA (see 224120). Majeed et al. (2000) concluded that the combination of CRMO characterized by early onset, aggressive course, and long duration with a new microcytic type of CDA represented a new autosomal recessive syndrome.
Majeed et al. (2001) reported a brother and sister, born into a consanguineous Arab family, who developed Majeed syndrome at 3 weeks and 2 months of age, respectively. The diagnosis of CRMO was confirmed by radiography and technetium isotope bone scans; bone marrow studies confirmed the diagnosis of CDA, which was hypochromic and microcytic on peripheral blood smears. At age 21, the brother still had active CRMO with frequent relapses; both patients' height and weight were below the 5th percentile. The first-cousin parents and 3 other sibs were unaffected.
Ferguson et al. (2005) noted that although Sweet syndrome was definitively diagnosed in only the 2 brothers reported by Majeed et al. (1989), the 2 cousins reported by Majeed et al. (1989, 2000) in that family had a history of rash that was consistent with Sweet syndrome. Ferguson et al. (2005) stated that the 2 affected sibs from the second family reported by Majeed et al. (2001) did not have Sweet syndrome, but 1 of them had a history of cutaneous pustulosis, and an obligate carrier from that family had severe psoriasis.
In 2 consanguineous Arab families with Majeed syndrome, previously reported by Majeed et al. (1989, 2000, 2001), Ferguson et al. (2005) identified homozygosity for a missense mutation (S734L; 605519.0001) and a 2-bp deletion (605519.0002) in the LPIN2 gene, respectively.
Ferguson, P. J., Chen, S., Tayeh, M. K., Ochoa, L., Leal, S. M., Pelet, A., Munnich, A., Lyonnet, S., Majeed, H. A., 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. 42: 551-557, 2005. [PubMed: 15994876] [Full Text: https://doi.org/10.1136/jmg.2005.030759]
Ferguson, P. J., El-Shanti, H. Majeed syndrome: a review of the clinical, genetic and immunologic features. Biomolecules 11: 367, 2021. [PubMed: 33670882] [Full Text: https://doi.org/10.3390/biom11030367]
Majeed, H. A., 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. Europ. J. Pediat. 160: 705-710, 2001. [PubMed: 11795677] [Full Text: https://doi.org/10.1007/s004310100799]
Majeed, H. A., El-Shanti, H., Al-Rimawa, H., Al-Masri, N. On mice and men: an autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia. (Letter) J. Pediat. 137: 441-442, 2000. [PubMed: 10969284] [Full Text: https://doi.org/10.1067/mpd.2000.107613]
Majeed, H. A., Kalaawi, M., Mohanty, D., Teebi, A. S., Tunjekar, M. F., Al-Gharbawy, F., Majeed, S. A., Al-Gazzar, A. H. 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, 1989. [PubMed: 2809904] [Full Text: https://doi.org/10.1016/s0022-3476(89)80650-x]