This project is a collaboration between researchers at Mount Sinai Medical Center, Harvard Medical School, Boston Children’s Hospital, and the National Institutes of Health to conduct genotype and phenotype analysis of patients with Moebius Syndrome and other related conditions. Moebius syndrome (MBS) is defined by limited eye abduction and facial paresis.

As part of the neuroimaging core, we performed a brain imaging study of MBS patients to investigate whether there are differences in diffusion derived metrics such as fractional anisotropy (FA) and mean diffusivity (MD) in patients with MBS as compared to the controls. In addition, we also looked at morphological brain differences between these patients and healthy controls.

Contribution/Role: Responsible for accurate scanning, processing, and analysis of diffusion tensor imaging (DTI) data. This research lead to a newly developed tensor based morphometry approach (D-TBM) which enables a better identification of morphological changes of individual white matter pathways compared to the available tools.

Findings:

1. The statistical results of D-TBM revealed volumetric reduction in the brainstem, specifically in the region that contains nuclei of cranial nerves VI, VII, and the medial longitudinal fasciculus which might explain the observed phenotypes. This area of volume reduction can serve as a biomarker, so far, we have been able to classify all the newly scanned Moebius subjects correctly using a Naïve Bayes classifier (Controls: ¹⁵⁄₁₅, and MBS ¹⁷⁄₁₇), achieving 100% sensitivity and specificity.
   
2. Many MBS patients have other abnormalities such as limb defect or mirror movements. Careful analysis of high quality DTI data of a subgroup of Moebius patients with mirror movements led to the discovery of less than normal pyramidal decussation. This observation led to the initiation of a new project to specifically recruit Moebius patients with mirror movements to further test this hypothesis. We also developed a DTI protocol specifically designed to scan the brainstem region to investigate this further.

Papers/abstracts: Paper under preparation to be submitted to NeuroImage. Abstract presented at Organization for Human Brain Mapping (OHBM 2017.

Presentation