Vici Syndrome

Overview

Vici syndrome is a rare and severe multisystem genetic disorder characterized by a combination of developmental and neurological abnormalities. First described in 1988, the syndrome is marked by features such as agenesis of the corpus callosum, cataracts, cardiomyopathy, immunodeficiency, and hypopigmentation of the skin and hair. It affects multiple organs and systems, often leading to significant developmental delays, recurrent infections, and early mortality. Vici syndrome is inherited in an autosomal recessive manner and remains a challenging condition with no curative treatment.

Causes

Vici syndrome is caused by mutations in the EPG5 gene, which plays a critical role in autophagy — a cellular process involved in breaking down and recycling damaged cellular components. Disruption of this process due to EPG5 mutations leads to widespread cellular dysfunction, particularly affecting the brain, muscles, immune system, and heart. The disorder follows an autosomal recessive inheritance pattern, meaning both copies of the gene must be mutated for the syndrome to manifest. Parents of an affected child are typically asymptomatic carriers.

Symptoms

The clinical presentation of Vici syndrome is complex and involves multiple organ systems. Common features include:

• Agenesis of the corpus callosum: Partial or complete absence of the structure connecting the two brain hemispheres, resulting in developmental delays

• Bilateral cataracts: Clouding of the lenses present at birth or in early infancy

• Cardiomyopathy: Most commonly hypertrophic cardiomyopathy, leading to cardiac complications

• Combined immunodeficiency: Leading to frequent and severe infections

• Hypopigmentation: Light-colored hair and skin due to melanin production defects

• Severe intellectual disability

• Hypotonia and delayed motor milestones

• Feeding difficulties and failure to thrive

• Hearing loss, seizures, and respiratory issues in some cases

Diagnosis

Diagnosis of Vici syndrome involves a combination of clinical, imaging, and genetic testing. Key steps include:

• Clinical evaluation: Recognition of hallmark features such as developmental delay, cataracts, hypopigmentation, and recurrent infections

• Brain imaging: MRI to detect agenesis of the corpus callosum and other structural abnormalities

• Cardiac assessment: Echocardiogram to evaluate for cardiomyopathy

• Ophthalmologic exam: To confirm the presence of cataracts and assess vision

• Immunological workup: To identify immune dysfunction and susceptibility to infections

• Genetic testing: Identification of pathogenic variants in the EPG5 gene confirms the diagnosis

Treatment

There is currently no cure for Vici syndrome. Management is supportive and focuses on addressing individual symptoms and improving quality of life through a multidisciplinary approach. Treatment may include:

• Cardiology care: Monitoring and managing cardiomyopathy with medications or supportive interventions

• Immunoglobulin replacement therapy: For patients with immunodeficiency to prevent infections

• Cataract surgery: To restore vision, if feasible

• Physical and occupational therapy: To assist with developmental delays and improve motor skills

• Feeding support: Nutritional interventions or feeding tubes for infants with failure to thrive

• Anticonvulsants: For those with seizure activity

• Multidisciplinary care team: Including neurologists, immunologists, cardiologists, ophthalmologists, and therapists

Prognosis

The prognosis for individuals with Vici syndrome is generally poor due to the multisystem nature of the disorder and the severity of complications. Most affected children have profound developmental delays and require lifelong medical support. Many patients do not survive beyond early childhood, although a few cases with longer survival have been reported. Early diagnosis, vigilant medical management, and comprehensive supportive care can improve quality of life and potentially extend survival.