Marinesco–Sjögren syndrome

Overview

Marinesco–Sjögren syndrome (MSS) is a rare, inherited, multisystem disorder characterized primarily by early-onset cerebellar ataxia, congenital cataracts, muscle weakness (myopathy), and intellectual disability. First described independently by Gheorghe Marinesco in Romania and Torsten Sjögren in Sweden in the 1930s, the syndrome affects both the central nervous system and skeletal muscles, along with other organs in some cases.

MSS typically presents in infancy or early childhood, with hallmark signs including developmental delay, difficulty with coordination and balance, and lens opacities (cataracts) that are present at or soon after birth. The condition progresses slowly and often requires lifelong management and supportive care. While rare, MSS has been reported across various populations and may be underdiagnosed due to overlapping symptoms with other neurological and muscular disorders.

Causes

Marinesco–Sjögren syndrome is most commonly caused by mutations in the SIL1 gene, located on chromosome 5q31. The SIL1 gene encodes a co-chaperone protein involved in proper protein folding within the endoplasmic reticulum. Mutations in this gene disrupt protein homeostasis, leading to cellular stress and damage, particularly in muscle and nerve cells.

The condition is inherited in an autosomal recessive manner, meaning an affected individual must inherit two copies of the mutated gene, one from each parent. Parents of a child with MSS are typically asymptomatic carriers. Other genes may also be implicated in cases without identifiable SIL1 mutations, suggesting genetic heterogeneity.

Symptoms

The clinical presentation of Marinesco–Sjögren syndrome is variable but often includes a recognizable combination of neurological, muscular, and ocular symptoms. Common features include:

• Cerebellar ataxia:

  • Appears in infancy or early childhood

  • Unsteady gait, poor balance, and coordination difficulties

  • Fine motor skill impairments

• Congenital cataracts:

  • Present at birth or shortly thereafter

  • May cause visual impairment or blindness if not treated early

• Myopathy (muscle weakness):

  • Proximal muscle weakness (affecting shoulders, hips)

  • Delayed motor milestones

  • Muscle wasting or hypotonia (low muscle tone)

• Intellectual disability:

  • Ranges from mild to moderate

  • Speech and language delays are common

• Additional features:

  • Short stature and growth delays

  • Skeletal abnormalities such as scoliosis

  • Delayed puberty or hypogonadism in some cases

  • Feeding difficulties and developmental regression (in rare cases)

While the core features are typically present in most cases, the severity and presence of additional symptoms can vary between individuals.

Diagnosis

Diagnosis of Marinesco–Sjögren syndrome involves a combination of clinical evaluation, neuroimaging, muscle testing, and genetic analysis. The following steps are commonly used:

• Clinical examination:

  • Assessment of neurological symptoms (ataxia, hypotonia)

  • Ophthalmologic evaluation for cataracts

  • Muscle strength testing and developmental assessment

• Neuroimaging:

  • Brain MRI often shows cerebellar atrophy, particularly in the vermis

• Muscle biopsy:

  • Shows myopathic changes with vacuoles or mitochondrial abnormalities

• Genetic testing:

  • Sequencing of the SIL1 gene to confirm the diagnosis

  • Whole-exome sequencing may be used if SIL1 mutations are not found

• Electromyography (EMG):

  • May reveal mild myopathic patterns

Early diagnosis is important to initiate appropriate therapies and interventions, particularly for cataracts and developmental support.

Treatment

There is currently no cure for Marinesco–Sjögren syndrome. Treatment is supportive and aims to improve quality of life and functional ability. Management typically involves a multidisciplinary team and includes:

• Ophthalmologic care:

  • Surgical removal of cataracts (lens replacement or extraction)

  • Ongoing vision therapy as needed

• Physical and occupational therapy:

  • Improves motor coordination, muscle strength, and balance

  • Assists with activities of daily living and adaptive strategies

• Speech and language therapy:

  • Supports communication development

  • Helps address feeding or swallowing difficulties

• Educational support:

  • Special education services for intellectual and learning challenges

• Endocrinological support:

  • Treatment for growth delays or hormonal deficiencies if present

• Regular monitoring:

  • Routine follow-ups with neurology, genetics, and rehabilitation services

Psychosocial support for families and caregivers is also essential, as the condition can place significant demands on family life and long-term planning.

Prognosis

The long-term prognosis of Marinesco–Sjögren syndrome varies depending on the severity of symptoms. While the condition is progressive, the rate of progression is typically slow. Most individuals survive into adulthood, although they may remain physically and intellectually dependent on caregivers.

With appropriate support and therapy, many patients can achieve developmental milestones, maintain mobility with assistance, and engage in social and educational activities. Cataract surgery significantly improves vision and quality of life when performed early.

Research into the molecular mechanisms of MSS and potential targeted therapies is ongoing, offering hope for future treatments. Genetic counseling is recommended for affected families to discuss recurrence risks and reproductive options.