What are the other Names for this Condition (Also known as /Synonyms)

• Chronic Recurrent Multifocal Osteomyelitis, Congenital Dyserythropoietic Anemia, and Neutrophilic Dermatosis Syndrome
• Congenital Dyserythropoietic Anemia and Chronic Recurrent Multifocal Osteomyelitis
• LPIN2-Related Majeed Syndrome

What is Majeed Syndrome? (Definition/Background Information)

• Majeed Syndrome is a rare autoinflammatory disease characterized by intermittent fevers, pustular rashes, anemia, and non-infectious osteomyelitis (inflammation of the bone marrow). A defect in the LPIN2 gene causes the disorder
• The onset of signs and symptoms is between 3 weeks to 2 years of age. Fevers that last a few days are accompanied by severe pain, with resolution and recurrence after normalcy. Systemic inflammation can cause growth delays in height and weight. The anemia is caused by congenital erythropoietic anemia (CDA). 
• The skin rashes are similar to those grouped as Sweets Syndrome, with biopsies showing superficial and deep clusters of neutrophils (a type of white blood cell), which show up clinically as pustules. A psoriasis-like rash is also sometimes noted
• Soft tissue swelling and pain occur near the joints. Bone pain is caused by inflammation in the bone marrow (osteomyelitis). No infectious cause is detected with bone biopsy. The episodes of bone marrow inflammation worsen and remit, termed Chronic Recurrent Multifocal Osteomyelitis (CRMO). Bone disease can cause severe pain, short stature, and contractures (stiffness and inflexibility) across joints.
• Majeed Syndrome is primarily managed through anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. The long-term prognosis varies, with some individuals experiencing symptom improvement with treatment while others may face ongoing challenges related to bone abnormalities and recurrent fevers

Who gets Majeed Syndrome? (Age and Sex Distribution)

• Patients with Majeed Syndrome are diagnosed in infancy or early childhood when the child is between three weeks to two years of life
• Majeed Syndrome is rare, with fourteen cases reported by consanguineous families.
• Both males and females are affected
• Thus far, cases of Majeed Syndrome from the Middle East, India, and Spain have been reported

What are the Risk Factors for Majeed Syndrome? (Predisposing Factors)

• Majeed Syndrome is more likely in those with a positive family history of the same
• Although a sporadic disease, being born to a consanguineous marriage confers a higher risk for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Majeed Syndrome? (Etiology)

A defect in the LPIN2 gene is the cause of Majeed Syndrome. A defect in each of the two gene copies of LPIN2 is required.

• The syndrome has an autosomal recessive (AR) inheritance. Thus, one defective gene is inherited from each parent, the mother and father
• Autosomal recessive diseases are more frequent in pairings with increased DNA similarities. Therefore, consanguineous marriages (between close relatives) are more likely to result in AR inheritance diseases.

What are the Signs and Symptoms of Majeed Syndrome?

The signs and symptoms of Majeed Syndrome may include:

• Intermittent high fevers, beginning in infancy or early childhood, are the initial sign of Majeed Syndrome. Fevers are accompanied by severe pain.
• Rash can be prominent, with pustules not caused by infection. It is not present in all patients with Majeed Syndrome.
• Swelling of the soft tissues at the joints is present
• Bone pain is a significant feature of Majeed Syndrome. On X-ray, areas of the bone marrow consistent with osteomyelitis are seen. On bone biopsy, microscopic evidence of inflammation is seen, with no bacterial, fungal, or other organisms. Cultures of the biopsy similarly grow no pathogenic organisms
• Over time, growth delays in height appear, and joint contractures
• Increased liver size (hepatomegaly) and jaundice are seen in the first months, which resolve spontaneously
• Anemia and low neutrophils (one of the white blood cell lines) appear in early childhood and can be severe.

How is Majeed Syndrome Diagnosed?

Majeed Syndrome is diagnosed based on the physical findings, laboratory tests, family history, and disease course.

• Exclusion of infectious causes for fever and recurrent multifocal osteomyelitis must be done.
• Blood tests for inflammatory markers, complete blood count, and others. 
• Imaging with X-rays or MRI is needed to evaluate the joint, bone, and bone marrow disease
• Biopsies of the skin and affected bone marrow, with examination by a pathologist.
• Genetic testing for the abnormal LPIN2 gene is confirmatory.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Majeed Syndrome?

Majeed Syndrome is a lifelong condition requiring ongoing care. Some of the complications may include:

• Growth retardation, with permanent short stature
• Severe anemia and neutropenia, requiring transfusions, and risk of secondary infection
• Poor quality of life from chronic inflammation and pain

How is Majeed Syndrome Treated?

The treatment for Majeed Syndrome may involve the following measures:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control fever but work poorly against Chronic Recurrent Multifocal Osteomyelitis (CRMO)
• Corticosteroids can help control the symptoms of Majeed Syndrome, but the long-term side effects limit their continuous use
• Tumor necrosis factor (TNF) inhibitors have been used in two patients without much benefit.
• Methotrexate has shown some improvement.
• Interleukin-1 beta inhibitors (canakinumab, rilonacept, anakinra) resolved the clinical symptoms, lowered inflammatory markers, and resolved CRMO in all four patients treated for the condition

How can Majeed Syndrome be Prevented?

Majeed Syndrome cannot be prevented, as it is a genetic disorder.

• For those known to carry the LPIN2 gene defect, genetic counseling can be offered
• Prenatal diagnosis of Majeed Syndrome is possible in families having the LPIN2 gene defect that has been identified

What is the Prognosis of Majeed Syndrome? (Outcomes/Resolutions)

• The prognosis of Majeed Syndrome has been poor because of the constant and progressive bone and hematologic disease.
• Thus far, the four patients treated with Interleukin-1 beta inhibitors have shown continued effectiveness, which may improve the prognosis

Additional and Relevant Useful Information for Majeed Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/