Majeed syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Majeed syndrome is a rare condition that is characterized by recurrent episodes of fever and inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, Majeed syndrome causes abnormal inflammation that can damage the body's tissues, particularly the bones and, less commonly, the skin. The signs and symptoms of Majeed syndrome typically appear in infancy or early childhood and can vary from person to person.

One of the major features of Majeed syndrome is an inflammatory bone condition known as chronic recurrent multifocal osteomyelitis (CRMO). This condition causes recurrent episodes of bone pain and joint swelling. These symptoms continue into adulthood, although they may improve for short periods. CRMO can lead to complications such as slow growth and the development of joint deformities called contractures, which restrict the movement of certain joints.

Another feature of Majeed syndrome is a blood disorder called congenital dyserythropoietic anemia. This disorder is one of many types of anemia, all of which involve a shortage of red blood cells. Without enough of these cells, the blood cannot carry an adequate supply of oxygen to the body's tissues. This can cause tiredness (fatigue), weakness, pale skin, and shortness of breath. The complications of congenital dyserythropoietic anemia can range from mild to severe.

Some people with Majeed syndrome develop an inflammatory disorder of the skin known as Sweet syndrome. The symptoms of Sweet syndrome include fever and the development of painful bumps or blisters on the face, neck, back, and arms.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the LPIN2 gene cause Majeed syndrome. This gene provides instructions for making a protein called lipin-2. Lipin-2 helps regulate the inflammatory response, the first step in the immune system's response to injury. Lipin-2 is also thought to play a role in bone remodeling, the process by which old bone is removed and replaced by new bone.

Variants in the LPIN2 gene alter the structure and function of lipin-2. Research into how these gene variants cause the specific signs and symptoms of Majeed syndrome is still ongoing. Changes in the lipin-2 protein cause people with Majeed syndrome to produce more molecules that promote inflammation. In addition, individuals with Majeed syndrome produce more osteoclasts, which are cells that break down bone tissue. In people with Majeed syndrome, the overly active immune response leads to chronic inflammation and fevers, while the increased production of osteoclasts leads to excessive bone inflammation and remodeling.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Majeed syndrome is rare; approximately 30 individuals with this condition have been reported in the literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal inflammatory response · Very frequent (99-80%)

Any anomaly of the inflammatory response, a response to injury or infection characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.

Abnormality of bone marrow cell morphology · Very frequent (99-80%)

An anomaly of the form or number of cells in the bone marrow.

Arthralgia · Very frequent (99-80%)

Joint pain.

Bone pain · Very frequent (99-80%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.

Cachexia · Very frequent (99-80%)

Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease.

Congenital hypoplastic anemia · Very frequent (99-80%)

A type of hypoplastic anemia with congenital onset.

Fever · Very frequent (99-80%)

Body temperature elevated above the normal range.

Hypochromic microcytic anemia · Very frequent (99-80%)

A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.

Other findings in the same source

From: Orphanet

Additional reported features include Metaphyseal irregularity (Very frequent (99-80%)); Osteomyelitis (Very frequent (99-80%)); Papule (Very frequent (99-80%)); Pustule (Very frequent (99-80%)); Weight loss (Very frequent (99-80%)); Acne (Frequent (79-30%)); Edema (Frequent (79-30%)); Failure to thrive (Frequent (79-30%)); Headache (Frequent (79-30%)); Hepatomegaly (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Majeed syndrome is Rheumatology, with a rheumatologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Majeed syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.