Introduction:
Vici syndrome is a rare and severe genetic disorder characterized by the principal features of callosal agenesis (congenital brain defect affecting a brain structure called corpus callosum), cataracts (appearance of the cloudy area over the lens of the eye), hypopigmentation of skin and hair, cardiomyopathy (disease affecting the heart muscles), and immunodeficiency (impaired immune function).
Other organs are less commonly affected. Approximately 100 individuals have been diagnosed with Vici syndrome. The main feature of this syndrome is brain abnormality occurring due to abnormal development of brain tissue called the corpus callosum. This can lead to developmental delay, acquired microcephaly (small head), and progressive failure to thrive. Whereas in some individuals additional multisystem involvement can be noted affecting other organs, including the liver, lungs, thyroid, and kidneys. In some cases, skeletal myopathy can also be noted. Most people with Vici syndrome may not survive past childhood. However, this can vary widely.
The main cause of Vici syndrome is the variation occurring in the EPG5 (encoding ectopic P granules protein 5) gene present in the chromosome 18q12.3. Mutations in the EPG5 gene can interfere with autophagy (the intercellular process by which the cells clean out any damaged or unnecessary components). Treatment for Vici syndrome mainly aims at supportive and symptomatic care. Still, a better understanding of the underlying genetic defect may aid in the development of targeted therapies in the future.
What Causes Vici Syndrome?
Mutations in the EPG5 gene are responsible for Vici syndrome. The EPG5 is present on chromosome 18q12.3. It consists of 44 exons with a length of 119,67 Kb (kilobase). The EPG5 gene is expressed primarily in the central nervous system, heart, skeletal muscle, thymus, lungs, cells of the immune system, and kidneys. This gene is responsible for the regulation of the autophagy pathway. Autophagy is a process by which dead unnecessary cell parts are recycled or broken down. In addition to autophagy, this gene aids in the immune response of the body to external organisms such as bacteria and viruses.
Changes in the EPG5 gene cause abnormal EPG5 protein production that does not respond to foreign bodies, causing recurrent infections and impaired autophagy. Any changes in the autophagy pathway can disrupt normal cell development. However, the reason behind the disruption of cells and the signs and symptoms of Vici syndrome need to be clearly understood. This condition can have an autosomal recessive pattern, meaning both genes in each cell must have undergone abnormal variations to cause this disorder. The affected individual's mother and father will also be caring for one copy of the altered gene, but they may not show any signs or symptoms of this condition.
What Are the Symptoms of Vici Syndrome?
Vici syndrome is a very rare genetic disorder that presents its symptoms in the first months of life. The main features of Vici syndrome are cataracts, cardiomyopathy, hypopigmentation of hair and skin, callosal agenesis, and immunodeficiency. However, various other additional features involving other organs have been reported.
1) Central Nervous System
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Delayed milestone development, such as sitting, crawling, and walking.
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Uncontrollable seizures.
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Acquired microcephaly (head circumference) is generally normal at birth, but progressive microcephaly can be noted later within the first year of life.
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Radiological abnormalities in Vici syndrome may include abnormally small cerebellum and brainstem, delayed myelin sheath formation, cortical malformations, cerebellar abnormalities, and a general reduction in white matter bulk.
2) Heart
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Cardiomyopathy—hypertrophic and dilated forms of cardiomyopathy are noted in many patients.
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Minor birth defects in the heart, such as atrial septal defects and persistent foramen ovale, have been reported.
3) Muscle
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Profound hypotonia (low muscle tone) can be present, affecting the strength and coordination of muscles.
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HyperCKemia (elevated creatine kinase (CK) levels) may indicate skeletal muscle, brain, or heart damage or degeneration.
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The disease affects the muscles that control voluntary movement in the body.
4) Eyes
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Cataracts affecting both eyes are one of the main diagnostic features of Vici syndrome.
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Various other signs affecting the eyes include nystagmus (rapid, uncontrollable eye movements), optic nerve hypoplasia, vision loss, and fundus hypopigmentation (less fundus pigmentation).
5) Hearing
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It can be due to the inner ear or the auditory nerve structures damage.
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This condition is often overlooked due to developmental delay and other multisystem involvement.
6) Immune System
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Immunodeficiency is one of the hallmark features of Vici syndrome. As the patient is immune deficient, the individual may experience recurrent infections, such as respiratory infections, which are very common during the early stages.
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Other commonly affected infections include mucocutaneous candidiasis, sepsis, gastroenteritis, urinary tract infections, bacterial conjunctivitis, and perineal abscesses.
7) Skin
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Children with Vici syndrome present with pale skin and very blonde hair.
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Some children have been reported to have an intermittent and extensive rash resembling Stevens-Johnson syndrome.
8) Lungs
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Respiratory infections are commonly noted in individuals affected by Vici syndrome.
9) Liver
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Hepatomegaly (abnormal liver enlargement) with or without liver dysfunction has been noted in patients with Vici syndrome.
10) Kidneys
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In individuals with Vici syndrome, kidney damage, hydronephrosis (kidneys become swollen due to urine build-up inside them), and renal tubular acidosis are seen.
What Is the Diagnostic Procedure for Vici Syndrome?
The diagnosis of Vici syndrome is based on suggestive clinical features. An extensive diagnostic procedure is required for the confirmation of Vici syndrome, which includes baseline investigations like immune function, thyroid function, liver function, and renal function tests; a chest x-ray to check for hypoplasia; an eye examination to check for cataracts; a cardiac ultrasound to check for cardiomyopathy or structural defects; and an MRI of the brain. Genetic testing is also done to check for mutations in the EPG5 gene.
What Is the Treatment for Vici Syndrome?
Currently, there is no cure for Vici syndrome. The treatment for the affected individual is largely supportive and aimed at treating the symptoms.
The general treatment options include:
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Surgery for cataracts, however, depends on the severity of the condition.
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Hearing aids may be of use.
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Control of seizures by anticonvulsant therapy.
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For cardiomyopathy, regular cardiac assessments will be required; this may benefit from proactive medical management.
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For immunodeficiency, regular intravenous immunoglobulin infusions and antimicrobial prophylaxis will be required.
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For hypothyroidism, thyroid hormone replacement may be required.
Conclusion:
Vici syndrome is a rare genetic disorder affecting individuals at their earliest stages of development. The syndrome is characterized by a combination of various features affecting different organs in the body. The main characteristics include callosal agenesis, hypopigmentation of the skin and hair, cardiomyopathy, cataracts, and immunodeficiency. The diagnosis of this condition is typically based on analyzing multiple factors such as patients' symptoms, genetic testing, and imaging studies. It is crucial to consult with a healthcare professional for a complete check-up and appropriate guidance.
