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Research paper

Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings

Four TBRS patients with structured MRI + DTI. Recurrent findings: corpus callosum anomalies, small posterior fossa, deep left Sylvian fissure, asymmetric uncinate / arcuate fascicles on tractography, increased cortical thickness. Periventricular FLAIR white-matter signal is not a recognized TBRS feature.

Indexed context

Jiménez de la Peña M, et al.

dnmt3atbrsneuroimagingcorpus-callosumcortical-thickness

Markdown path

content/research/papers/2024-jimenez-tbrs-neuroimaging.md

Findings

Four TBRS patients with structured MRI + DTI. Recurrent findings: corpus callosum anomalies, small posterior fossa, deep left Sylvian fissure, asymmetric uncinate / arcuate fascicles on tractography, increased cortical thickness. Periventricular FLAIR white-matter signal is not a recognized TBRS feature.

Why it may matter for Levi

Levi's MRI pattern (nonspecific R>L periventricular FLAIR, otherwise unremarkable) does not match the published TBRS imaging gestalt — modestly negative for TBRS. But TBRS-typical features require morphometric / DTI reads to detect and may have been missed on general pediatric MRI read; argues for expanding the scope of the specialized neuroradiology re-read to include TBRS screening (corpus callosum, posterior fossa, cortical thickness, tract asymmetry) alongside mosaic mTORopathy screening.

Paper text

Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings

Jiménez de la Peña M, et al. — American Journal of Medical Genetics Part A (2024). https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.63434 / PubMed

Findings summary

Four patients with de novo DNMT3A pathogenic variants had detailed brain MRI (including DTI and 3D-SPGRT1) with structured morphometric analysis. Reported structural findings present across the cohort included:

  • Corpus callosum anomalies in all four.
  • Small posterior fossa (with Chiari-related morphology in some).
  • Deep left Sylvian fissure.
  • Asymmetry of the uncinate and arcuate fascicles on DTI tractography.
  • Marked increased cortical thickness.

The authors propose that structural imaging features are routinely under-recognized in TBRS and that these findings should be searched for deliberately. Prior TBRS literature had described only occasional ventriculomegaly or Chiari. The specific finding of symmetric periventricular deep white-matter FLAIR signal is not a TBRS-defining radiologic feature in the published literature to date; an isolated thalamic FLAIR hyperintensity was reported in one 2026 Saudi TBRS case, but that is a deep-grey-matter finding rather than periventricular white-matter.

Relevance to Levi

Levi's April 7, 2026 brain MRI is structurally unremarkable except for nonspecific patchy periventricular deep white-matter FLAIR signal, right > left, with hippocampi normal and MRS unremarkable. That specific pattern is not a recognized TBRS imaging signature. However, the published TBRS imaging features (corpus callosum anomalies, small posterior fossa, asymmetric arcuate / uncinate fascicles, increased cortical thickness) require dedicated morphometric or DTI readings to detect and are the kind of findings a general pediatric MRI read will often miss. This argues for explicitly adding "screen for TBRS-type neuroimaging features" (corpus callosum, posterior fossa morphology, cortical thickness, tractography asymmetry) to the pediatric-neuroradiology re-read already prioritized in Levi's diagnostics workspace, alongside the mosaic mTORopathy re-read it is currently scoped for.

Provenance