On this page
Olmsted syndrome
This condition primarily affects the skin, leading to painful calluses and fissures. It can also involve hair, nails, and other parts of the body, significantly impacting quality of life for affected individuals, typically from infancy or early childhood.
Available at Jeen Health
Clinical tests that include this
Overview
Olmsted syndrome is a very rare inherited condition that primarily affects the skin. The most prominent feature is a type of skin thickening known as palmoplantar keratoderma, which means the skin on the palms of the hands and soles of the feet becomes unusually thick and hardened [PMID:24076378]. This can lead to discomfort, pain, and difficulty with movement. The syndrome can also affect other areas of the body, sometimes causing hair loss (alopecia), nail abnormalities, and problems with other organs.
The condition typically appears in infancy or early childhood and tends to worsen over time. Due to its rarity, the exact number of people affected by Olmsted syndrome is not well established. Management focuses on alleviating symptoms and improving quality of life for those living with the condition.
Symptoms & clinical features
The hallmark symptom of Olmsted syndrome is severe, progressive palmoplantar keratoderma. The thickened skin can develop painful cracks, known as fissures, which are prone to infection [PMID:24076378]. In some individuals, the thickening may spread beyond the palms and soles to areas like the knees, elbows, and around the mouth (periorificial keratoderma).
Beyond the primary skin features, individuals with Olmsted syndrome may experience other symptoms. These can include abnormalities of the hair, such as patchy or complete hair loss (alopecia), and problems with the nails, making them thick or brittle. Some individuals may also have dental anomalies, deafness, or corneal changes in the eyes [PMID:24076378]. The severity and combination of these symptoms can vary significantly among affected individuals, even within the same family.
Video: Genetics 101
Affected organs
The skin is the primary organ affected in Olmsted syndrome, particularly on the hands and feet. The excessive skin thickening (keratoderma) is the defining characteristic. However, the condition can also involve other tissues derived from the ectoderm, the outermost germ layer during embryonic development.
Organs that may be secondarily affected include the hair follicles, leading to alopecia, and the nails, causing various dystrophies. In some cases, sensory organs like the ears (leading to hearing loss) and eyes (corneal abnormalities) may also be involved. Less commonly, teeth can show developmental issues. The range of affected organs highlights the systemic nature of some forms of Olmsted syndrome, rather than it being purely a skin disorder.
Risks & severity
Olmsted syndrome presents with a variable spectrum of severity, even within families. The condition typically begins in infancy or early childhood and is progressive, meaning symptoms tend to worsen over time if not managed. The severe palmoplantar keratoderma can cause significant pain, limit mobility, and lead to recurrent infections in skin fissures. This can substantially impact daily activities and quality of life.
While the condition is primarily dermatological, some forms are associated with additional features such as hearing loss, developmental delays, or corneal changes, which can further increase the complexity and severity of the syndrome. There is also an increased risk of developing squamous cell carcinoma in affected skin areas for some individuals, requiring careful monitoring [PMID:23719003]. The specific genetic cause can sometimes influence the overall severity and potential associated risks.
Genetic causes
Olmsted syndrome is a genetic condition, meaning it is caused by changes in specific genes. Two genes have been identified as being associated with Olmsted syndrome: TRPV3 and MBTPS2. These genes play important roles in different cellular processes.
Pathogenic variants in TRPV3 (transient receptor potential cation channel subfamily V member 3) are a common cause of Olmsted syndrome. The TRPV3 gene provides instructions for making a protein that acts as an ion channel, which is involved in various cell functions, including skin development and sensation [PMID:24076378]. Changes in TRPV3 can lead to abnormal regulation of keratinocyte (skin cell) growth and differentiation, resulting in the characteristic skin thickening. More recently, variants in MBTPS2 (membrane bound transcription factor peptidase, site 2) have also been linked to some cases of Olmsted syndrome [PMID:23719003]. The MBTPS2 gene is involved in processing certain proteins that regulate cell stress responses and lipid metabolism, which are crucial for maintaining healthy skin.
- MBTPS2 membrane bound transcription factor peptidase, site 2
- TRPV3 transient receptor potential cation channel subfamily V member 3
Inheritance pattern
Olmsted syndrome can be inherited in different ways, depending on the specific genetic cause. It can follow an autosomal dominant (AD) inheritance pattern, or an autosomal recessive (AR) pattern. In autosomal dominant inheritance, only one copy of a changed gene in each cell is enough to cause the condition. This means that an affected person has a 50% chance of passing the condition on to each child. In these cases, the condition often appears to be 'de novo', meaning the genetic change occurred for the first time in the affected individual and was not inherited from a parent.
For autosomal recessive inheritance, an individual must inherit two changed copies of the gene (one from each parent) to develop the condition. People who have only one changed copy are called carriers and typically do not show symptoms. When both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two changed copies and be affected by Olmsted syndrome. Genetic counselling can help families understand their specific inheritance risk and reproductive options.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of Olmsted syndrome typically begins with a clinical assessment of the characteristic skin features, particularly the severe palmoplantar and periorificial keratoderma, often combined with other features like alopecia or nail abnormalities. Given its rarity, a definitive diagnosis usually relies on genetic testing.
Referrals for genetic testing in the UK are often made by a dermatologist or a clinical geneticist. Genetic testing can identify pathogenic variants in genes such as TRPV3 or MBTPS2. The NHS Genomic Medicine Service offers genomic testing for rare diseases, and this condition would typically fall under an R-code for inherited disorders of the skin. A clinical geneticist or genetic counsellor can help coordinate appropriate testing and interpret the results within the family context.
Management & lifestyle
Management of Olmsted syndrome focuses on alleviating symptoms and preventing complications, as there is currently no cure. Treatment strategies are individualised based on the severity and specific manifestations of the condition. For the skin, regular use of emollients and keratolytics (creams that soften and shed the thickened skin) can help reduce discomfort and improve skin texture. Topical or systemic retinoids may also be considered in some cases to help control skin cell growth.
Pain management is crucial, especially for painful fissures, and preventing infection in cracked skin is important. Regular follow-up with a dermatologist is recommended to monitor skin changes and manage any associated risks, such as the potential for squamous cell carcinoma. Other symptoms, like hearing loss, may require specific interventions such as hearing aids. A multidisciplinary team approach, involving dermatologists, geneticists, and other specialists as needed, is often beneficial to provide comprehensive care within the NHS framework. Genetic counsellors can provide valuable support and information to affected individuals and their families.
UK care pathway
In the UK, individuals suspected of having Olmsted syndrome would typically be referred to a consultant dermatologist for initial assessment and then to a clinical genetics service. These services are part of the NHS Genomic Medicine Service (GMS) network. Clinical geneticists and genetic counsellors provide expert advice, coordinate genetic testing - which would be accessed via relevant R-codes for inherited skin disorders on the NHS National Genomic Test Directory - and offer support to patients and their families. This pathway ensures access to specialist diagnostic and management expertise.
Frequently asked questions
Is Olmsted syndrome always inherited from my parents?
Not always. While it can be inherited from one or both parents depending on the specific gene involved, some cases are 'de novo', meaning the genetic change happens for the first time in the affected individual and was not inherited from either parent.
What kind of doctors treat Olmsted syndrome in the UK?
In the UK, a dermatologist would typically manage the skin symptoms. A clinical geneticist would also be involved to confirm the diagnosis through genetic testing and provide genetic counselling. Other specialists, such as ear, nose and throat (ENT) doctors or ophthalmologists, might be involved depending on the specific symptoms.
Can Olmsted syndrome be cured?
Currently, there is no known cure for Olmsted syndrome. Management focuses on treating the symptoms, such as the skin thickening and pain, and preventing complications to improve the individual's quality of life. Research is ongoing into the underlying causes and potential new therapies.
What is the long-term outlook for someone with Olmsted syndrome?
The long-term outlook varies greatly depending on the severity of symptoms and the presence of any associated features. While the condition is lifelong and progressive, consistent management of skin symptoms and regular monitoring can help reduce discomfort and prevent complications. Regular follow-up with specialists is important for ongoing care.
Are there any support groups for Olmsted syndrome in the UK?
Due to its rarity, specific UK support groups solely for Olmsted syndrome might be limited. However, organisations like the British Association of Dermatologists or rare disease charities may offer resources and connect individuals with similar skin conditions or rare genetic disorders. Your genetic counsellor might also be able to provide information on available support.
References
- Song Z, Gao M, Li T. TRPV3-Activated PARP1/AIFM1/MIF Axis through Oxidative Stress Contributes to Atopic Dermatitis. The Journal of investigative dermatology. 2024. PMID: 38823435
- Huang YY, Li JH. Olmsted Syndrome. JAMA dermatology. 2024. PMID: 38055272
- Bhayana AA, Prasad P, Bhayana AA. Olmsted syndrome. Indian journal of ophthalmology. 2022. PMID: 35791241
- Lu A, Li K, Huang C. Pathogenesis and management of TRPV3-related Olmsted syndrome. Frontiers in genetics. 2024. PMID: 39748945
- Weinberg RL, Kim S, Pang Z. Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2024. PMID: 38866482
- Duchatelet S, Hovnanian A. Olmsted syndrome: clinical, molecular and therapeutic aspects. Orphanet journal of rare diseases. 2015. PMID: 25886873
- Elise Tonoli R, De Villa D, Hübner Frainer R. Olmsted syndrome. Case reports in dermatological medicine. 2012. PMID: 23320205
- Kumar P, Sharma PK, Kar HK. Olmsted syndrome. Indian journal of dermatology. 2008. PMID: 19881998