Clinical Presentation and Molecular Characterization of 3 Patients with Vici Syndrome: Two Novel Variants in the <i>EPG5</i> Gene

Abstract

<b><i>Introduction:</i></b> Vici syndrome is an ultra-rare, congenital disorder of autophagy characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Patients usually present in the neonatal period or infancy with profound hypotonia, based on information available from the nearly 100 cases reported to date. <b><i>Case Presentation:</i></b> We present 3 new cases of Vici syndrome confirmed by genetic analysis of <i>EPG5</i> gene. The 3 male patients had neonatal hypotonia, progressive microcephaly, psychomotor retardation, recurrent respiratory tract infections, optic atrophy, and failure to thrive, but no cataracts or hepatomegaly. Three disease-causing variants in homozygous state were detected in the <i>EPG5</i> gene: two novel c.1652C&gt;T and c.7557+2T&gt;C forms; and one previously reported c.7447C&gt;T. The patient, who was homozygous for the c.1652C&gt;T mutation, presented with neonatal onset seizures that had not been reported previously. <b><i>Discussion/Conclusion:</i></b> The present study provides data for the evaluation of the natural history and genotype-phenotype correlations for treatment options that are expected to be available in the future.