Phenotypic expansion of EGP5-related Vici syndrome: 15 Dutch patients carrying a founder variant

Eur J Paediatr Neurol. 2022 Nov:41:91-98. doi: 10.1016/j.ejpn.2022.11.003. Epub 2022 Nov 12.


Vici syndrome (OMIM 242840) is a very rare autosomal recessive multisystem disorder first described in 1988. In 2013, bi-allelic loss-of-function mutations in EPG5 were reported to cause Vici syndrome. Five principal diagnostic features of Vici syndrome have been proposed: agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. We identified 15 patients carrying a homozygous founder missense variant in EPG5 who all exhibit a less severe clinical phenotype than classic Vici syndrome. All 15 show typical brain abnormalities on MRI. The homozygous founder variant in EPG5 they carry results in a shorter in-frame transcript and truncated, but likely still residual, EPG5 protein. We speculate that the residual EPG5 protein explains their attenuated phenotype, which is consistent with two previous observations that low expression of EPG5 can lead to an attenuated Vici syndrome phenotype. We propose renaming this condition EPG5-related neurodevelopmental disorder to emphasize the clinical variability of patients with bi-allelic mutations in EPG5.

Keywords: Attenuated phenotype; Brain MRI; EPG5; Vici syndrome.

MeSH terms

  • Autophagy-Related Proteins
  • Cataract* / genetics
  • Corpus Callosum
  • Homozygote
  • Humans
  • Phenotype
  • Vesicular Transport Proteins / genetics


  • EPG5 protein, human
  • Autophagy-Related Proteins
  • Vesicular Transport Proteins

Supplementary concepts

  • Absent corpus callosum cataract immunodeficiency