Brain and spine MRI findings in children presenting with TMCO1 mutation.

Abstract

Cerebrofaciothoracic dysplasia (CFTD) is a developmental disorder characterized by distinctive craniofacial dysmorphism, global developmental delay, and skeletal anomalies. CTFD is the result of biallelic autosomal recessive loss of function mutations in the transmembrane and coiled-coil domains one protein (TMCO1) gene. Based on a population of 27 molecularly confirmed cases, classic brain morphologies associated with CFTD have been described in the literature. Previous studies have demonstrated only mild ventriculomegaly, corpus callosum abnormalities, frontotemporal atrophy, and three cases of associated epilepsy. We present previously undescribed brain MRI findings in two children presenting with seizures due to TMCO1 mutation. MR Imaging demonstrated hippocampal malrotation, olfactory bulb agenesis and olfactory sulcus hypoplasia in both children, pontine hypoplasia, and cochlear nerve agenesis in one child. We demonstrate that TMCO1 may play a more extensive and previously undescribed role in neurodevelopment thereby expanding the phenotype associated with CFTD.