title: Vici syndrome: a review.
abstract: Vici syndrome [OMIM242840] is a severe, recessively inherited congenital disorder characterized by the principal features of callosal agenesis, cataracts, oculocutaneous hypopigmentation, cardiomyopathy, and a combined immunodeficiency. Profound developmental delay, progressive failure to thrive and acquired microcephaly are almost universal, suggesting an evolving (neuro) degenerative component. In most patients there is additional variable multisystem involvement that may affect virtually any organ system, including lungs, thyroid, liver and kidneys. A skeletal myopathy is consistently associated, and characterized by marked fibre type disproportion, increase in internal nuclei, numerous vacuoles, abnormal mitochondria and glycogen storage. Life expectancy is markedly reduced.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 conserved throughout evolution with important roles in the removal of defective proteins and organelles, defence against infections and adaptation to changing metabolic demands. Almost 40 EPG mutations have been identified to date, most of them truncating and private to individual families.The differential diagnosis of Vici syndrome includes a number of syndromes with overlapping clinical features, neurological and metabolic disorders with shared CNS abnormalities (in particular callosal agenesis), and primary neuromuscular disorders with a similar muscle biopsy appearance. Vici syndrome is also the most typical example of a novel group of inherited neurometabolic conditions, congenital disorders of autophagy.Management is currently largely supportive and symptomatic but better understanding of the underlying autophagy defect will hopefully inform the development of targeted therapies in future.
authors.affiliation: Department of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Division of Metabolism and Laboratory of Molecular Medicine, Bambino Gesu Children's Hospital IRCCS, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Smith
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gautel
authors.affiliation: Department of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK. Heinz.Jungbluth@gstt.nhs.uk.|Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK. Heinz.Jungbluth@gstt.nhs.uk.|Department of Clinical and Basic Neuroscience, IoPPN, King's College, London, UK. Heinz.Jungbluth@gstt.nhs.uk.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002386:Cataract / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D006801:Humans; D051907:Lysosomal Membrane Proteins; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; C000592185:EPG5 protein, human; D051907:Lysosomal Membrane Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins