We present novel brain MRI findings in 2 children presenting with seizures due to TMCO1 mutation. Both children had absent olfactory bulbs and olfactory tracts and hippocampal malrotation. EEG demonstrated right temporal slow waves and intermittent focal slowing. One child had pontine hypoplasia, hypoplasia of bilateral optic nerves/chiasm, and an absent right cochlear nerve. In both children, there was increased mineralization in bilateral globi pallidi and bilateral substantia nigra on SWI sequence, possibly from excessive calcium. Ventriculomegaly and cavum septum pellucidum were also present in both children. Spine MRI revealed segmentation abnormalities including partial fusion of T2/T3 vertebral bodies and fusion of the posterior elements of T3-T5. Both children exhibited dysplastic and bifid ribs, demonstrating partial posterior fusion. Right renal agenesis was also noted in one child. TMCO1 mutation results in cerebro-facio-thoracic dysplasia (CFTD) due to abnormal calcium homeostasis. The transmembrane and coiled-coil domains 1 protein directs formation of endoplasmic reticulum calcium leak channels which facilitate calcium leak upon overload of the endoplasmic reticulum. Failure of calcium leak results in abnormal cell function resulting in delayed osteogenesis, reduced mitochondrial volume, reduced mitochondrial respiration, and decreased endoplasmic reticulum stress mediated apoptosis. These children have distinctive craniofacial dysmorphism, global developmental delay, and skeletal anomalies. Previous studies have demonstrated only mild ventriculomegaly, corpus callosum abnormalities, frontotemporal atrophy, and three cases of associated epilepsy. Olfactory bulb agenesis may be due to abnormal development of the cribriform plate of the ethmoid and failure of olfactory nerves to induce development of the olfactory bulb from the telencephalon. We demonstrate that TMCO1 may play a more extensive and previously undescribed role in neurodevelopment, specifically in the formation of the hippocampus, optic nerve, and pons. Read More

Meeting name: SPR 2022 Annual Meeting & Postgraduate Course , 2022

Authors: Ratnayake Charith, Subramanian Subramanian, Narayanan Srikala, Gaesser Jenna

Keywords: Pediatric, Dysplasia, MRI

Understanding anatomy and embryology is crucial for evaluation of olfactory epithelium, olfactory nerve, olfactory bulb and olfactory cortex pathology. We will discuss various imaging modalities available to evaluate olfactory system and discuss role of fMRI and Diffusion tensor imaging of olfactory system. Fetal MRI can identify olfactory bulb and olfactory sulci after 30weeks of gestation consistently and can be helpful in diagnosis of charge syndrome. Various congenital CNS malformations associated with olfactory system abnormalities like CHARGE, Holoprosencephaly, Kallmann syndrome, Acrocallosal syndrome, frontal encephalocele and sphenoidal encephalocele will be presented. Traumatic injury to cribriform plate of ethmoid can result in transection of olfactory nerve resulting in anosmia. Primary tumors of olfactory epithelium, esthesioneuroblastoma and secondary involvement of olfactory epithelim by rhabdomyosarcoma will be presented. Various tumors that can involve olfactory cortex namely DNET, ganglioglioma and pilocytic astrocytoma will be presented. References: Booth TN, Rollins NK. Spectrum of clinical and associated MR findings in children with olfactory anomalies. Am J Neuroradiol.2016; 37:1541-48 Blustajn J, Krisch CFE, Panigrahy A, Netchine I. Olfactory anomalies in CHARGE syndrome: Imaging findings of a potential major diagnostic criterion. Am J Neuroradiol.2008; 29:1266-69. Read More

Meeting name: SPR 2019 Annual Meeting & Postgraduate Course , 2019

Authors: Lori Schoenbrun, Subramanian Subramanian, Rajan Deepa, Gaesser Jenna, Lo Cecilia, Schmithorst Vincent, Panigrahy Ashok

Keywords: Olfactory system, Olfactory sulcus, Olfactory Bulb