Vici syndrome is a rare, severe congenital disorder affecting multiple body systems from early life. It is characterized by abnormalities of the brain, immune system, heart, skin, and eyes, presenting significant challenges.
Key Clinical Features
Vici syndrome is characterized by five principal features: agenesis of the corpus callosum, cardiomyopathy, cataracts, hypopigmentation, and immunodeficiency. These features are consistently present and influence the health of affected individuals.
Agenesis of the corpus callosum
Agenesis of the corpus callosum is the partial or complete absence of the brain structure connecting the two cerebral hemispheres. This brain abnormality contributes to profound developmental delays and intellectual disability. Affected infants often display weak muscle tone and do not achieve milestones like rolling or sitting independently.
Cardiomyopathy
Cardiomyopathy, a heart muscle disease, is common and life-threatening in children with Vici syndrome, affecting approximately 80% of cases. It impairs the heart’s ability to pump blood efficiently and often worsens over time. Some individuals may also have congenital heart defects, such as ventricular septal defects.
Cataracts
Cataracts, a clouding of the eye lenses, are a defining feature, present at birth or developing in early infancy. These eye abnormalities reduce vision. Bilateral cataracts are a common diagnostic finding.
Hypopigmentation
Hypopigmentation manifests as skin, hair, and eye colors lighter than those of other family members. This oculocutaneous hypopigmentation is a visual characteristic of the syndrome.
Immunodeficiency
Immunodeficiency leads to recurrent and life-threatening infections. Respiratory, gastrointestinal, and urinary tract infections are common. This compromised immune function makes individuals highly susceptible to severe illness.
Beyond these five primary characteristics, other symptoms include seizures, hearing loss, and feeding difficulties. Affected infants grow and gain weight more slowly than expected. Distinctive facial features, such as a small jaw or prominent forehead, may also be present.
Genetic Basis
Vici syndrome is caused by mutations in the EPG5 gene, located on chromosome 18q12.3. This gene provides instructions for making the EPG5 protein, which plays a role in autophagy. Autophagy is the body’s cellular recycling system, breaking down defective proteins and organelles, defending against infections, and adapting to metabolic demands. When the EPG5 gene is mutated, this process is disrupted, leading to the symptoms of Vici syndrome.
Vici syndrome is inherited in an autosomal recessive pattern. A child must inherit two copies of the mutated EPG5 gene—one from each parent—to develop the condition. Parents carrying one copy of the altered gene are asymptomatic.
Diagnostic Process
Diagnosis of Vici syndrome begins with recognizing its characteristic clinical features in an infant or young child. Healthcare providers observe the combination of brain, heart, and eye abnormalities, hypopigmentation, and recurrent infections.
Medical tests confirm these findings. Brain imaging, such as MRI, identifies agenesis of the corpus callosum and other brain developmental issues. An echocardiogram assesses heart structure and function to detect cardiomyopathy. An ophthalmologic examination identifies cataracts.
Blood tests evaluate immune system function and identify deficiencies. Definitive diagnosis is confirmed through genetic testing, which analyzes DNA to identify mutations within the EPG5 gene.
Multidisciplinary Management
There is no cure for Vici syndrome; management focuses on addressing symptoms and providing supportive care. A coordinated multidisciplinary team of specialists provides individualized care.
Neurologists manage seizures and developmental delays. Cardiologists monitor and treat heart conditions like cardiomyopathy. Immunologists oversee the weakened immune system, preventing and treating recurrent infections, sometimes with immunoglobulin therapy. Ophthalmologists manage vision issues, including cataracts.
Physical and occupational therapies help with motor skills and development. Nutritional support, often requiring a feeding tube, is necessary due to feeding difficulties and failure to thrive. Management also includes prompt treatment of infections and monitoring for other organ involvement.
Long-Term Outlook
Vici syndrome is a severe condition that profoundly impacts development and reduces life expectancy. Its multisystem involvement contributes to a poor prognosis.
Many children with Vici syndrome do not survive beyond early childhood. This is primarily due to complications from progressive cardiomyopathy and severe, recurrent infections. Ongoing research aims to understand the underlying genetic and cellular defects. Improved supportive care and evolving research work towards enhancing the quality of life for individuals with this syndrome.