Majeed Syndrome

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.

Clinical Features

Majeed et al. (1989) reported 2 brothers and a female cousin who had chronic recurrent multifocal osteomyelitis (CRMO; 259680) and congenital dyserythropoietic anemia (CDA); the brothers also had neutrophilic dermatosis or Sweet syndrome (608068). 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.

Molecular Genetics

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.