On this page
Majeed syndrome
This rare genetic disorder, typically appearing in early childhood, causes inflammation throughout the body. It primarily affects the bones, skin, and can lead to recurrent episodes of fever. The condition is inherited in an autosomal recessive manner.
Overview
Majeed syndrome is a very rare autoinflammatory disorder, meaning it involves an overactive immune system that mistakenly attacks the body's own tissues, leading to inflammation [PMID:16027004]. The main features of Majeed syndrome include chronic recurrent multifocal osteomyelitis (CRMO), which is inflammation of multiple bones, a specific type of skin inflammation known as neutrophilic dermatosis, and recurrent fevers. This condition usually becomes apparent in early childhood, often before the age of two years [PMID:16027004].
Autoinflammatory disorders are distinct from autoimmune diseases. In autoinflammatory conditions, the innate immune system (the body's first line of defence) is dysregulated, leading to unprovoked inflammation. Unlike autoimmune diseases, they typically do not involve high levels of autoantibodies, which are antibodies that target the body's own proteins.
Symptoms & clinical features
The hallmark symptoms of Majeed syndrome typically emerge during infancy or early childhood. Chronic recurrent multifocal osteomyelitis (CRMO) is a key feature, involving persistent or recurring bone pain and swelling. Multiple bones can be affected, and these episodes of bone inflammation can be painful [PMID:24607130].
Skin manifestations are also common, often presenting as a neutrophilic dermatosis. This involves skin lesions that can appear as red, painful plaques or pustules. Other symptoms include recurrent episodes of fever, which may be accompanied by general feelings of being unwell (malaise), joint pain (arthralgia), and short stature. Some individuals may also develop anaemia, which is a reduction in red blood cells [PMID:16027004].
Video: Genetics 101
Affected organs
Majeed syndrome primarily affects the skeletal system, leading to inflammation in multiple bones (osteomyelitis). The long bones, such as those in the arms and legs, are commonly involved, but any bone can be affected. The skin is also significantly impacted, exhibiting characteristic inflammatory lesions.
Beyond these, the condition can also cause systemic inflammation, leading to recurrent fevers. The immune system itself is dysregulated. In some cases, there may be effects on blood cell production, contributing to anaemia.
Risks & severity
Majeed syndrome is considered a severe, chronic condition, as its symptoms, particularly bone pain and inflammation, can significantly impact quality of life from a young age. The severity can vary between individuals, but the recurrent nature of the symptoms often requires ongoing management. Without appropriate treatment, chronic inflammation can lead to long-term complications, such as bone deformities or impaired growth.
Due to its very rare nature, exact prevalence figures for Majeed syndrome are not well established. The condition typically manifests within the first two years of life, though onset can occasionally occur later in early childhood. The ongoing inflammation can contribute to issues like anaemia and may affect growth in children.
Genetic causes
Majeed syndrome is caused by pathogenic variants in the LPIN2 gene [PMID:16027004]. The LPIN2 gene provides instructions for making a protein called lipin 2. Lipin proteins play important roles in fat metabolism, helping to process and store fats in the body. They are also thought to be involved in regulating inflammation.
When there are disease-causing changes in the LPIN2 gene, the lipin 2 protein either does not function correctly or is not produced in sufficient quantities. This disruption is believed to lead to the uncontrolled inflammation observed in Majeed syndrome, although the precise mechanism linking LPIN2 dysfunction to the specific symptoms of bone and skin inflammation is still an area of research.
- LPIN2 lipin 2
Inheritance pattern
Majeed syndrome is inherited in an autosomal recessive pattern. This means that a person must inherit two altered copies of the LPIN2 gene, one from each parent, to develop the condition. Individuals who inherit only one altered copy of the LPIN2 gene are known as carriers. Carriers typically do not show symptoms of Majeed syndrome themselves because their one functional copy of the gene is usually sufficient to prevent the condition.
When two carriers of an LPIN2 gene variant have children, there is a 25% chance with each pregnancy that their child will inherit two altered copies of the gene and therefore develop Majeed syndrome. There is a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two working copies of the gene and not be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Majeed syndrome typically begins with a clinical evaluation based on the characteristic symptoms of chronic recurrent multifocal osteomyelitis, neutrophilic dermatosis, and recurrent fevers appearing in early childhood. Imaging studies, such as X-rays or MRI scans, can help identify bone lesions.
Confirmation of Majeed syndrome is achieved through genetic testing, which identifies pathogenic variants in the LPIN2 gene. Such testing is available through the NHS Genomic Medicine Service (GMS) via the Rare and Inherited Disease testing directory, often under an appropriate R-code for autoinflammatory conditions. Referrals for genetic testing and counselling are usually made by a paediatrician, rheumatologist, or clinical geneticist.
Management & lifestyle
Management of Majeed syndrome focuses on controlling inflammation and alleviating symptoms to improve quality of life. This often involves the use of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used for pain and fever control. For more severe or persistent inflammation, disease-modifying anti-rheumatic drugs (DMARDs) or biological therapies that target specific parts of the immune system may be considered. Anakinra, an interleukin-1 receptor antagonist, has shown some benefit in managing symptoms for some individuals [PMID:24607130].
Treatment plans are highly individualised and are typically managed by a multidisciplinary team, including paediatricians, rheumatologists, and pain management specialists. Regular monitoring for disease activity, growth, and potential complications is an important part of ongoing care. Genetic counselling is also recommended for affected individuals and their families to understand the inheritance pattern and implications for family planning.
UK care pathway
In the UK, individuals with suspected Majeed syndrome are typically referred to specialist paediatric or rheumatology services within the NHS. If a genetic cause is suspected, patients can be referred to a Clinical Genetics service. Genetic testing for rare inherited conditions, including Majeed syndrome, is available through the NHS Genomic Medicine Service (GMS).
Genetic counsellors play a vital role in providing information and support to families undergoing genetic testing, explaining results, and discussing the implications for the patient and other family members. The relevant R-codes within the NHS GMS testing directory would be used to guide appropriate genetic investigations for autoinflammatory disorders.
Frequently asked questions
What does 'autoinflammatory' mean?
Autoinflammatory means the immune system becomes overactive and causes inflammation without an obvious external trigger like an infection. It's different from autoimmune diseases, where the immune system creates antibodies against the body's own tissues.
Will my child definitely get Majeed syndrome if I am a carrier?
No, if you are a carrier for Majeed syndrome, you have one altered copy of the LPIN2 gene but typically do not have the condition. For your child to develop Majeed syndrome, they would need to inherit an altered copy of the gene from both parents. If both parents are carriers, there is a 25% chance with each pregnancy that their child will be affected.
Can Majeed syndrome be cured?
Currently, there is no cure for Majeed syndrome. However, treatments are available to manage the symptoms, reduce inflammation, and improve quality of life. These treatments focus on controlling the overactive immune response.
How is Majeed syndrome treated in children?
Treatment for children with Majeed syndrome is individualised and often involves anti-inflammatory medications, such as NSAIDs or more targeted biological therapies. These aim to reduce bone pain, skin inflammation, and fever episodes. Care is typically provided by a team of specialist doctors.
What is chronic recurrent multifocal osteomyelitis (CRMO)?
CRMO is a condition where areas of bone become inflamed, causing pain and swelling. In Majeed syndrome, this inflammation can affect multiple bones and tends to recur over time, which is why it's called 'chronic recurrent multifocal'.
References
- Adam MP, Bick S, Mirzaa GM. LPIN2-Related Majeed Syndrome. 1993. PMID: 36877799
- Haşlak F, Akay N, Gül Ü. Autoinflammatory Bone Diseases. Balkan medical journal. 2025. PMID: 39757386
- Ferguson PJ, El-Shanti H. Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features. Biomolecules. 2021. PMID: 33670882
- Stern SM, Ferguson PJ. Autoinflammatory bone diseases. Rheumatic diseases clinics of North America. 2013. PMID: 24182852
- Morbach H, Hedrich CM, Beer M. Autoinflammatory bone disorders. Clinical immunology (Orlando, Fla.). 2013. PMID: 23369460
- Wang S, Yu T, He X. Clinical and genetic analysis of Majeed syndrome caused by LPIN2 complex heterozygous mutation and literature review. Frontiers in pediatrics. 2025. PMID: 41113563
- Ferguson PJ, El-Shanti HI. Autoinflammatory bone disorders. Current opinion in rheumatology. 2007. PMID: 17762617
- Badiger VA, Balan S, Madan S. LPIN2 -related Majeed syndrome: report of two Indian patients with novel variants in LPIN2 and review of literature. Clinical dysmorphology. 2024. PMID: 37865862