EPG5-Related Disorders in Seven New Patients: Refining the Phenotypic Spectrum and Insights on Phenotype-Genotype Correlations
摘要
Pathogenic variants in EPG5 have been associated with Vici syndrome (OMIM #242840) characterized by agenesis of the corpus callosum (ACC), cataracts, cardiomyopathy, hypopigmentation, and immunodeficiency as hallmark features. Additional variable features include microcephaly, hypotonia, developmental delay, and growth retardation. Recently, few reports described milder cases with a neurodevelopmental phenotype and less systemic involvement harboring EPG5 variants suggesting a broader clinical spectrum. Herein, we describe seven patients from six unrelated Egyptian families in whom exome sequencing identified six homozygous (five novel and one previously reported) EPG5 variants. Patients presented with global developmental delay, microcephaly, hypotonia, dystonia, and failure to thrive. Seizures were evident in two patients and showed a variable response to antiepileptic drugs. Fair color of hair and skin was noted in four out of seven patients (57%), while cataracts and cardiomyopathy were observed in one patient each (14%). In addition to ACC, cerebellar and pontine hypoplasia, delayed myelination, and ventricular dilatation were evident in all patients. Interestingly, deep fissure in the frontal lobes, extending from the frontal horn to the frontal pole, was documented in six patients and appears to represent a characteristic feature associated with EPG5 variants. Our study highlights the phenotypic variability associated with EPG5 variants and emphasizes the presence of a phenotypic spectrum ranging from the classic severe Vici syndrome to a neurodevelopmental disorder with less systemic manifestations and a longer survival rate.