Background

Vici syndrome (VICIS) refers to a clinical spectrum of multiple organ systems characterized by corpus callosum agenesis, hypopigmentation, cataracts, cardiomyopathy and immunodeficiency. The aims of this study were to describe detailed clinical and molecular features of two Chinese female siblings and to review several previous findings.

Methods

Targeted sequencing panel involving all known disease-causing genes of monogenic disorders combined with Sanger sequencing validation were performed to identify the likely pathogenic sequence variants of the proband with VICIS.

Results

The proband diagnosed as VICIS presented with neonatal pneumonia, myocardial damage, hypotonia, maxillofacial malformations, hearing impairment, failure to thrive and died 40 days after birth. Two novel missense variants in ectopic P-granules autophagy protein 5 homolog (EPG5, NM_020964.3) were identified in this proband. The two likely pathogenic variants c.1609G>A (p.(E537K)) and c.5764C>G (p.(P1922A)) were assessed as damaging by bioinformatic analysis. As these variants were absent in 150 unrelated Chinese normal controls and inherited from asymptomatic parents in the co-segregation analysis, the compound heterozygous EPG5 variants were responsible for the clinical features of this patient. Finally, she was genetically diagnosed with VICIS.

Conclusions

To our knowledge, this is the first Chinese case of VICIS. Our report identified novel compound heterozygous EPG5 sequence variants in the proband with VICIS, highlighting the rarity and high mortality rate of VICIS and emphasizing on the importance of high-throughput sequencing in confirmed diagnosis of monogenic diseases, which could further facilitate the development of genetic counseling and prenatal diagnosis.