Vici syndrome is a rare condition associated with a severe congenital multisystem disorder. It is characterized by the primary symptoms of agenesis of the corpus callosum, oculocutaneous, cardiomyopathy, cataracts, hypopigmentation, and combined immunodeficiency.
The syndrome causes a significant delay in development, acquired microcephaly and progressive failure to thrive. Most patients exhibit additional variable multi system problems.
This rare disease is diagnosed in the early years of an infant's life. Vici syndrome symptoms may vary, but prominent diagnostic features are evident from the onset; they sometimes evolve. Kids diagnosed with the syndrome experience difficulties in feeding and swallowing, leading to stunted growth.
Cataract is the most frequent visual abnormality, though other patients may develop optic nerve hypoplasia, photophobia, and nystagmus.
Other people develop hypopigmentation of the hair and the eyes, depending on one's ethnic or familial background. Cardiomyopathy evolves, causing heart failure. Infants suffer from recurrent infections that affect the gastrointestinal tract and the respiratory and urinary systems. The infections also include sepsis, conjunctivitis, and mucocutaneous candidiasis.
Skeletal muscle deformities may also develop like motor developmental delay and hypotonia. Other patients display facial abnormalities like cleft lip and micrognathia or the rare dysmorphic symptom. Sensorineural hearing loss is also evident in some people who suffer from the syndrome, though it is often underdiagnosed.
Other structural CNS deformities include retardation, psychomotor, and seizures with evidence of hematological malfunctions. Death of patients suffering from the condition is often associated with heart failure or other severe infections.
The syndrome is caused by a recessive mutation of the EPG5 gene. EPG5 gene encodes ectopic P-granules protein 5, an essential autophagy regulator in humans. It is located in the 18q12.3 chromosome and is primarily expressed in the skeletal muscles, CNS, lungs, kidneys, thymus, heart, and cells of the immune system.
The autophagy process involves certain steps that evolve from the formation of phagophores to autophagosomes, which combine with lysosomes to form the final structures of degradation-autolysosomes. The mutation of EPG5 gene is what disrupts this process.
There is a 97% chance of all the symptoms manifesting. An eighty-nine percent sensitivity for the presence of the EPG5 mutation is necessary to allow concrete decisions about genetic testing.
Journals about the Syndrome
Carlo Dionisi-Vici was the first person to write about the syndrome in 1988. The piece explained the case of two brothers who suffered from the disease. It was then that the condition acquired the name Vici Syndrome. The article spawned write-ups of other texts about the disorder.
A decade later, del Camp et al. wrote a piece that described the clinical features that were evident in four patients (two siblings, a male, and a female), which were similar to the Syndrome. In 2007, a report of two brothers diagnosed with the syndrome showed they suffered from renal tubular acidosis.
In 2015, Dr. Evangelos Axiotis wrote a doctoral thesis that explained the molecular mechanism and role of mutations in EPG5 and how they disrupt the function of the immune system in patients suffering from the syndrome.
Diagnosing the Syndrome
Diagnosis primarily depends on the presence of characteristic clinical symptoms. A brain MRI, for example, shows the presence of agenesis of the corpus callosum while an eye examination identifies cataracts and other visual deformities.
An electrocardiogram is useful in determining the function of the heart. Other diagnoses like molecular genetic testing, immunological analysis, and mutations of the EPG5 gene should confirm the diagnosis. Families with a history of disease causing mutations should perform prenatal diagnosis on their children.
Remington Steele Kelsch, a young boy who was born in October 15th, 2015 was diagnosed with the condition right after birth. He went through different surgeries to save his life from the complications that come with the syndrome. However, he succumbed to the disease the following year on May 31st, 2016.
Advances in Clinical Research
Apart from the notable symptoms highlighted in the earlier section of the discussion, researchers continue to conduct more clinical trials. In 2013, clinical trials determined the primary cause of the syndrome was associated with mutations in the EPG5 gene. Further research showed the ophthalmologic characteristics of the syndrome in 2014.
Treatment and Management
There is no definite cure for the syndrome, hence management is purely supportive with the aim of eliminating the effects of general multisystem involvement. An anticonvulsant therapy is performed on patients with seizures. Tube feeding is necessary on people with eating difficulties while antibiotics are administered in patients who have intercurrent infections.
Antimicrobial prophylaxis and Intravenous immunoglobin replacement treatments are considered for patients who suffer from severe immune system problems. However, since some features evolve, subsequent examinations, such as cardiac ultrasounds, lab tests to assess the immune system, liver, renal, and thyroid function should be performed at intervals.
In some cases, patients found to have cataracts may undergo surgery to improve their vision. This requirement should be determined on an individual basis, depending on the severity of the condition and expected prognosis. Patients who have hypothyroidism may require thyroid hormone replacement while those suffering from renal dysfunction need active management.
Genetic counseling makes an important aspect of managing the condition in families diagnosed with the syndrome. Today, hospitals perform mutational analysis and testing of the EPG5 chromosome on a diagnostic basis to families where the syndrome is identified.
Parents who want to determine the presence of the syndrome in a fetus should conduct a fetal MRI. It is because other imaging processes like fetal ultrasound may yield false results (both positive and negative), especially when used to detect collosol agenesis.
Vici Syndrome is a rare genetical disorder characterized by multi-system failure and various CNS anomalies. Unfortunately, the condition is not preventable and the only course of treatment so far is palliative care. However, the latest research reveals that gene therapy might be the best chance of offering an infant the chance of living a health life.