FBXL4-Related Mitochondrial DNA Depletion Syndrome 13 (MTDPS13): A Case Report With a Comprehensive Mutation Review

Mitochondrial DNA depletion syndromes (MTDPS) are a group of rare genetic disorders caused by defects in multiple genes involved in mitochondrial DNA (mtDNA) maintenance. Among those, FBXL4 mutations result in the encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13; OMIM #615471), which commonly presents as a combination of failure to thrive, neurodevelopmental delays, encephalopathy, hypotonia, and persistent lactic acidosis. We report here the case of a Lebanese infant presenting to us with profound neurodevelopmental delays, generalized hypotonia, facial dysmorphic features, and extreme emaciation. Whole-exome sequencing (WES) showed the girl as having MTDPS13 with an underlying FBXL4 missense mutation that has been previously reported only twice in unrelated individuals (c.1303C > T). Comprehensive literature search marked our patient as being the 94th case of MTDPS13 reported to date worldwide, and the first from Lebanon. We include at the end of this report a comprehensive mutation review table of all the pathological FBXL4 mutations reported in the literature, using it to highlight, for the first time, a possible founder effect of Arab origins to the disorder, being most prevalent in patients of Arab descent as shown in our mutation table. Finally, we provide a direct comparison of the disorder's clinical manifestations across two unrelated patients harboring the same disease-causing mutation as our patient, emphasizing the remarkable variability in genotype-to-phenotype correlation characteristic of the disease

Primary diffuse cerebral leptomeningeal atypical teratoid rhabdoid tumor: report of the first case

Atypical teratoid rhabdoid tumor (AT/RT) of the central nervous system has been recently described as a distinct clinicopathological entity with characteristic morphologic, immunophenotypic and molecular characteristics. AT/RT typically involves the posterior fossa of the pediatric population. Supratentorial AT/RT is exceedingly rare. In this report, we describe a very unusual case of a child who presented with signs and symptoms suggestive of leptomeningitis. However, imaging studies and histologic findings showed plaque-like AT/RT involving the leptomeninges of the cerebrum, cerebellum, and spinal cord. The disease proved to be rapidly fatal and resulted in the patient's death within approximately two weeks. To our knowledge, this is the first case of primary leptomeningeal AT/RT involving the supratentorial leptomeninges

Pre- and post-therapy assessment of clinical outcomes and white matter integrity in autism spectrum disorder: Pilot study

Objective: This pilot study aims to identify white matter (WM) tract abnormalities in Autism Spectrum Disorders (ASD) toddlers and pre-schoolers by Diffusion Tensor Imaging (DTI), and, to correlate imaging findings with clinical improvement after early interventional and Applied Behaviour Analysis (ABA) therapies by Verbal Behaviour Milestones Assessment and Placement Program (VB-MAPP). Methods: DTI scans were performed on 17 ASD toddlers/pre-schoolers and seven age-matched controls. Nine ASD patients had follow-up MRI twelve months following early intervention and ABA therapy. VB-MAPP was assessed and compared at diagnosis, six and twelve months after therapies. Tract-Based Spatial Statistics (TBSS) was used to measure fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial (RD) diffusivity Results: VB-MAPP scores improved at six and twelve months after early intervention and ABA therapy compared to scores at baseline. TBSS analysis showed significant FA decrease and/or RD increase in ASD patients before therapy versus controls in inferior fronto-occipital fasciculi, uncinate fasciculi, left superior fronto-occipital fasciculus, forceps minor, left superior fronto-occipital fasciculus, right superior longitudinal fasciculus, corona radiata bilaterally and left external capsule. A significantly FA increase in 21 tracts and ROIs is reported in post- versus pre-therapy DTI analysis. Conclusion: DTI findings highlighted ASD patient WM abnormalities at diagnosis and confirmed the benefits of twelve months of early intervention and ABA therapy on clinical and neuro imaging outcomes