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Autopsy findings in EPG5 ‐related Vici syndrome with antenatal onset
Author(s) -
Touraine Renaud,
Laquerrière Annie,
Petcu CarmenAdina,
Marguet Florent,
Byrne Susan,
Mein Rachael,
Yau Shu,
Mohammed Shehla,
Guibaud Laurent,
Gautel Mathias,
Jungbluth Heinz
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38342
Subject(s) - hypopigmentation , medicine , failure to thrive , cataracts , microcephaly , agenesis , pathology , pediatrics , dermatology , anatomy , ophthalmology
Vici syndrome is one of the most extensive inherited human multisystem disorders and due to recessive mutations in EPG5 encoding a key autophagy regulator with a crucial role in autophagosome–lysosome fusion. The condition presents usually early in life, with features of severe global developmental delay, profound failure to thrive, (acquired) microcephaly, callosal agenesis, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. Clinical course is variable but usually progressive and associated with high mortality. Here, we present a fetus, offspring of consanguineous parents, in whom callosal agenesis and other developmental brain abnormalities were detected on fetal ultrasound scan (US) and subsequent MRI scan in the second trimester. Postmortem examination performed after medically indicated termination of pregnancy confirmed CNS abnormalities and provided additional evidence for skin hypopigmentation, nascent cataracts, and hypertrophic cardiomyopathy. Genetic testing prompted by a suggestive combination of features revealed a homozygous EPG5 mutation (c.5870‐1G>A) predicted to cause aberrant splicing of the EPG5 transcript. Our findings expand the phenotypical spectrum of EPG5 ‐related Vici syndrome and suggest that this severe condition may already present in utero. While callosal agenesis is not an uncommon finding in fetal medicine, additional presence of hypopigmentation, cataracts and cardiomyopathy is rare and should prompt EPG5 testing.