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Marinesco-Sjögren syndrome
This rare genetic condition primarily affects the nervous system, leading to difficulties with coordination and movement, eye problems, and developmental delays. It typically becomes apparent in early childhood and has a significant impact on daily life.
Overview
Marinesco-Sjögren syndrome (MSS) is a rare genetic condition that primarily affects the brain, muscles, and eyes [PMID:33671239]. Individuals with MSS often experience a combination of symptoms including ataxia (problems with coordination and balance), muscle weakness, early-onset cataracts, and intellectual disability. The condition typically manifests in infancy or early childhood and can vary in severity among affected individuals. As it is a progressive condition, symptoms may worsen over time [PMID:20301712].
Symptoms & clinical features
The symptoms of Marinesco-Sjögren syndrome usually become noticeable during infancy or early childhood. Key features often include cerebellar ataxia, which affects balance and coordination, making walking difficult and often leading to frequent falls. Muscle weakness, particularly in the limbs, is also common, along with speech difficulties (dysarthria) [PMID:33671239]. Many individuals develop cataracts, clouding of the eye lens, which can lead to vision impairment and typically require surgical intervention at a young age. Other symptoms may include short stature, skeletal abnormalities such as scoliosis (curvature of the spine), and difficulties with learning and development, ranging from mild to severe intellectual disability.
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Affected organs
Marinesco-Sjögren syndrome primarily affects the central nervous system, particularly the cerebellum, which is crucial for movement coordination. This leads to the characteristic ataxia. Muscles throughout the body can also be affected, resulting in weakness. The eyes are commonly involved, with cataracts being a prominent feature. Additionally, the condition can impact bone development, leading to skeletal changes, and may also affect the endocrine system, contributing to short stature. The brain's overall development is also influenced, leading to varying degrees of intellectual disability.
Risks & severity
Marinesco-Sjögren syndrome is a progressive condition, meaning that its symptoms may gradually worsen over time, particularly the ataxia and muscle weakness. The severity of the condition can vary significantly between individuals. Some may experience more pronounced physical challenges and intellectual disability, while others might have milder forms [PMID:20301712]. Life expectancy can be reduced due to complications such as recurrent respiratory infections or severe neurological impairment. The age of onset for symptoms is typically in early childhood, often before the age of two, with cataracts sometimes presenting as early as infancy.
Genetic causes
Marinesco-Sjögren syndrome is a genetic condition, which means it is caused by changes in specific genes. At present, the most commonly identified genetic cause is pathogenic variants in the *SIL1* gene. The *SIL1* gene provides instructions for making a protein that plays a role in protein folding within cells, particularly in a cellular compartment called the endoplasmic reticulum. This process is vital for ensuring proteins are correctly shaped to perform their functions. When the *SIL1* gene has pathogenic variants, the protein folding process can be disrupted, leading to a build-up of misfolded proteins and cellular stress, especially in nerve cells [PMID:20301712]. This disruption is thought to contribute to the neurological and muscular problems seen in MSS.
Inheritance pattern
Marinesco-Sjögren syndrome is inherited in an autosomal recessive pattern. This means that a person must inherit two altered copies of the causative gene - one from each parent - to develop the condition. Individuals who have only one altered copy of the gene are called carriers; they typically do not show symptoms of the condition themselves but can pass the altered gene copy on to their children. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two altered gene copies and develop MSS. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two working copies of the gene and not be affected or 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 Marinesco-Sjögren syndrome is often suspected based on the characteristic clinical features, including ataxia, early-onset cataracts, and intellectual disability. Confirmation of the diagnosis typically involves genetic testing to identify pathogenic variants in the *SIL1* gene, or other genes associated with similar clinical presentations. In the UK, genetic testing for suspected inherited neurological conditions may be accessed via the NHS Genomic Medicine Service. A referral to a clinical genetics service or specialist paediatric neurologist would generally be the pathway to initiating such testing. The specific genetic test for this condition may be covered by an NHS National Genomic Test Directory R-code, such as R86 (Intellectual disability) or R310 (Early onset progressive ataxia).
Management & lifestyle
While there is currently no cure for Marinesco-Sjögren syndrome, management focuses on addressing symptoms and improving quality of life. This often involves a multidisciplinary team approach. Physical therapy and occupational therapy can help manage muscle weakness and improve mobility and daily living skills. Speech therapy may be beneficial for communication difficulties. Early surgical removal of cataracts is usually necessary to preserve vision. Regular monitoring for scoliosis and other skeletal issues is important. Educational support and special schooling may be required for individuals with intellectual disability. Genetic counsellors can provide information and support to families regarding the inheritance pattern and implications of the condition.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like Marinesco-Sjögren syndrome would typically be referred to a clinical genetics service, often by their GP or a specialist paediatrician or neurologist. These services are part of the NHS Genomic Medicine Service. Here, genetic counsellors and clinical geneticists can provide information, assess family history, and arrange for appropriate genetic testing, which may include whole genome sequencing or targeted gene panels. The NHS National Genomic Test Directory outlines the genetic tests available for specific conditions, identified by R-codes, to ensure consistent and high-quality genomic testing across the country. Genetic counsellors offer crucial support, explaining complex genetic information and helping families understand the implications of a diagnosis.
Frequently asked questions
What is the typical life expectancy for someone with Marinesco-Sjögren syndrome?
Life expectancy can vary significantly depending on the severity of the condition and the presence of complications. While some individuals may have a reduced life expectancy due to severe neurological impairment or respiratory issues, others may live into adulthood with appropriate supportive care.
Can Marinesco-Sjögren syndrome be prevented?
As Marinesco-Sjögren syndrome is a genetic condition, it cannot be prevented. For families with a history of the condition, genetic counselling can provide information on inheritance patterns and reproductive options, including prenatal testing if desired.
How common is Marinesco-Sjögren syndrome?
Marinesco-Sjögren syndrome is a very rare condition. The exact prevalence is not well established, but it is considered to affect only a small number of individuals worldwide. This rarity often means that healthcare professionals may not initially recognise the condition.
Are there any treatments to stop the progression of the disease?
Currently, there is no treatment that can stop the progression of Marinesco-Sjögren syndrome. Management focuses on treating symptoms and providing supportive care to improve quality of life. This includes therapies such as physiotherapy, occupational therapy, and speech therapy, as well as surgical intervention for cataracts.
What kind of support is available for families affected by MSS in the UK?
Families in the UK can access support through clinical genetics services, rare disease support groups, and charities. Genetic counsellors provide crucial information and emotional support. Various NHS services, including therapy teams and educational support, are also available to help manage the condition's impact on daily life.
References
- Adam MP, Bick S, Mirzaa GM. Marinesco-Sjögren Syndrome. 1993. PMID: 20301371
- Kalaydjieva L. Congenital cataracts-facial dysmorphism-neuropathy. Orphanet journal of rare diseases. 2006. PMID: 16939648
- Aslan ES, Eslamkhah S, Akcali N. Marinesco-Sjögren Syndrome: A Novel SIL1 Variant with In Silico Analysis and Review of the Literature. Life (Basel, Switzerland). 2025. PMID: 41465794
- Merlini L. Marinesco-Sjogren syndrome, fanfare, and more. Neuromuscular disorders : NMD. 2008. PMID: 18207737
- Haugarvoll K, Johansson S, Rodriguez CE. GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies. PloS one. 2017. PMID: 28052128
- Ruggieri AG, Marinakis NM, Amodei L. A Novel SIL1 Variant (p.E342K) Associated with Marinesco-Sjögren Syndrome Impairs Protein Stability and Function. International journal of molecular sciences. 2025. PMID: 41373471
- Buchignani B, Vega G, Pasquariello R. Muscle Imaging Approaches in Marinesco-Sjögren Syndrome: A Systematic Review and Two New Clinical Reports. Children (Basel, Switzerland). 2026. PMID: 41897072
- Superneau DW, Wertelecki W, Zellweger H. Myopathy in Marinesco-Sjogren syndrome. European neurology. 1987. PMID: 3469098