[P3-151] Clinical heterogeneity of genetically confirmed nine patients with Vici syndrome
Vici syndrome (VICIS: OMIM #242840) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum (ACC), cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical and genetic features of nine Japanese patients with VICIS. Genetic dissection of these nine patients from seven families identified 14 causative mutations in EPG5. These included five nonsense, two frameshift, three splicing, one missense, and one multi-exon deletion mutations, and two initiation codon variants. In our study, all patients had ACC, profound developmental delay and recurrent infections, seven patients had hypopigmentation, three patients had cardiac involvement, and no patients had cataracts, while progressive microcephaly, failure to thrive, epilepsy, high-arched palate and elevated AST/ALT were exhibited in most patients. Muscle biopsies showed only mild myopathic changes. VICIS should be suspected in any child with ACC and profound developmental delay, even if some of the principle features are absent. Cultured skin fibroblasts (SFs) from two affected patients demonstrated partial autophagic dysfunction, confirming the defects in autophagy in the patients.