Clinical Guidance
With the current widespread use of multigene panels and comprehensive genomic testing, it has become apparent that the phenotypic spectrum of biallelic EPG5 pathogenic variants causing EPG5-related disorder represents a continuum of variable severity. Vici syndrome (defined as a neurodevelopmental disorder with multisystem involvement characterized by the combination of agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive; see Suggestive Findings, ) is at the most severe end of the spectrum; however, milder, attenuated neurodevelopmental phenotypes with a variable degree of multisystem involvement are increasingly recognized. To date, around 90 individuals have been identified with biallelic EPG5 pathogenic variants. These reports have mostly shown individuals toward the more severe end of the phenotypic spectrum, while reports of individuals with only neurologic disease but no more extensive multisystem involvement are scarce . Several sub-phenotypes (e.g., those presenting with predominantly immunologic features) remain very likely underdiagnosed and should be carefully evaluated in future genotype-phenotype correlation studies. The description of the phenotypic spectrum associated with EPG5-related disorders is based on clinical reports published to date . Table 2. EPG5-Related Disorder: Frequency of Select Features Feature | % of Personsw/Feature Most common findings
Brain malformations | Corpus callosum agenesis or thinning | |
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