Dionisi Vici Sabetta Gambarara Syndrome

At a glance

It is a rare congenital multisystem disorder characterized by the presence of agenesis of the corpus callosum, severe developmental delay, immunodeficiency, cleft lip/palate, cataract, hypopigmentation, and progressive cardiomyopathy. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy. Vici Syndrome is the most typical example of a novel group of inherited neurometabolic conditions classified as congenital disorders of autophagy. Life expectancy is markedly reduced and usually death occurs before the age of 3 years due to cardiac failure or severe infection.

Synonym

Immunodeficiency Cleft Palate Cataract Hypopigmentation and Corpus Callosum Agenesis Syndrome; Vici Syndrome.

Incidence

Fewer than 10 cases have been reported in the literature.

Genetic inheritance

It is an autosomal recessive disorder. Vici Syndrome is due to recessive mutations in EPG5 on chromosome 18q12.3, encoding ectopic P granules protein 5 (EPG5), a key autophagy regulator in higher organisms. Autophagy is a fundamental cellular degradative pathway important to the removal of defective proteins and organelles, defense against infections and adaptation to changing metabolic demands.

Pathophysiology

Unknown. There is speculation about a defect involving the embryogenic organization of both the CNS and the immune system such as regulating gene products.

Diagnosis

Clinical findings and combined immunodeficiency with reduced IgG levels (particularly IgG2 subclass), normal IgA and IgM levels, and low number of circulating T lymphocytes, mainly T₄.

Clinical aspects

Affected individuals present profound developmental delay associated with agenesis of the corpus callosum, microcephaly, hypotonia (myopathy), severe seizure activities, and, occasionally, severe hypoplasia of the cerebellar vermis. Cortical dysplasia and schizencephaly have been described. One of the main features of this syndrome is a combined immunodeficiency with decreased levels of T₄ lymphocytes and serum IgG. This is a result of profound hypoplasia of the thymus and the peripheral lymphoid tissue. Activity of the natural killer cells, however, was reported to be normal. Recurrent infections, particularly pulmonary infections (partially also related to recurrent aspirations) and chronic mucocutaneous candidiasis, are a consequence of this immunodeficiency. The disease is also characterized by hypopigmentation of skin, hair, and retina. Cataract, nystagmus, unilateral or bilateral cleft lip/palate, micrognathia, and postnatal growth retardation are other, but inconstant, features. Cardiac involvement can occur in the form of endocardial fibroelastosis and/or progressive cardiomyopathy with dilatation or hypertrophy of the left ventricle. None of the reported patients has survived beyond the age of 3 years. Death from cardiac failure has been described, but most often death is the result of bronchopneumonia.

Precautions before anesthesia

Patients are most often booked for percutaneous gastric tube insertion secondary to failure to thrive. Request a chest radiograph to rule out respiratory tract ...