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Case 10

C Dunham, J Bush, M Sargent, E Roland, M Salvarinova

BC Children’s Hospital, Vancouver, British Columbia, Canada

Twenty hours after delivery, this previously term infant girl began feeding poorly and became less active. A further deterioration was noted eleven hours later and included low temperature and lethargy, ultimately leading to respiratory support requiring intubation. Short periods of left arm jerking were noted and head ultrasound suggested dysgenesis of the corpus callosum.

The infant was subsequently transferred to BCCH for further workup and was noted to be encephalopathic with a decreased level of consciousness, hypotonic, apneic, small sluggish pupils and absent gag/corneal reflexes. Vigorous stimulation garnered very little response. Brainz monitoring revealed a rhythmic burst-suppression pattern and subclinical seizures. MRI on the third day of life reiterated dysgenesis of the corpus callosum, but also uncovered numerous foci of T2 hyperintensity in the white matter including the frontal lobes, cerebellum, and brainstem. These white matter changes were accentuated on diffusion weight imaging, particularly in the “dorsal tegmental tracts” and the anterior cerebral peduncles, the latter of which extended superiorly toward the Rolandic cortex. In addition, a lack of normal T1/T2 signalling was seen in the posterior limbs of the internal capsule. An extensive metabolic workup was performed and suggested a diagnostic result that was confirmed on genetic testing of the proband.

Materials submitted:

One H&E/LFB stained digital slide of the right parasagittal cerebellum, and one digital picture compiling four coronal sections from the time of brain cutting .




What is the most likely underlying mutation?