case_images: PMC3157359_01
case_images: Nerve excitability profile of Case 2.. In the nerve excitability profile, there was an abnormally enhanced late subexcitability of the recovery cycle (A) and a pronounced S2 accommodation and reduced TEd (90-100 ms) value at the end of the depolarising threshold electrotonus (upper trace in B). C,D: scatter plots of these nerve excitability parameters in the patient (filled circle) and 16 normal controls (open symbols). Dashed lines (A-D) show 95% confidence interval of the normal range. See Text S1 for detailed description of methods.
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case_images: Nerve excitability testing in the patient showed several abnormalities (Figure 1) which are also observed in patients with EA1.
case_images: Attenuation of subcutaneous fat in Case 3.. (A) Coronal T2-weighted image showing the patient has attenuation of scalp subcutaneous fat (arrows). (B) Normal appearance in a patient with epilepsy without 17q12 deletion (arrows). Subcutaneous scalp fat was present on cranial MRI in 150 patients with temporal lobe epilepsy who did not carry this deletion.
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case_images: Cranial MRI showed right hippocampal sclerosis (Figure S2). Histopathology of the lobectomy specimen confirmed hippocampal sclerosis, without mossy fibre sprouting (Figure S2). Re-inspection of his cranial MRI showed attenuation of subcutaneous fat deposits (Figure 2).
case_images: Cerebellar atrophy in Case 3.. T1-weighted MRI reveals cerebellar atrophy. Note this is a T1-weighted image (not a T2-weighted image as in Figure 2A); the bright layer in the scalp is diploe, not subcutaneous fat.
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case_images: The alternative interpretation of an increased flux through the citrate synthetic (tricarboxylic acid cycle) pathway is unlikely, because his mitochondrial beta-oxidation is normal at rest and normally-suppressed through the OGTT (as reflected by dynamic total and fractional acyl-carnitine levels, Figure S3). His cranial MRI aged 28 showed mild cerebellar atrophy (Figure 3). Facial dysmorphism was confirmed by quantitative analysis in comparison with 200 age-, sex- and ethnicity-matched controls (Figure 6, Video S3).
case_images: Neuropathology of resection specimen from Case 3.. In the deep white (periventricular region) of the temporal lobectomy specimen of Case 3, a single cluster of globoid cells with granular cytoplasm was present. The cells showed PAS positivity, which could indicate glycogen storage, but the cells did not contain myelin debris and there was no evidence of demyelination. The cells were only present focally. Further investigation regarding histogenesis of these cells and characterization of cytoplasmic contents was not possible. Similar cell types were not noted in the hippocampus.
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case_images: Review of the tissue resected at temporal lobectomy of Case 3 showed a few cells deep in the temporal lobe white matter that contained abnormal storage material, that was PAS-positive, suggestive of excessive glycosylation (Figure 4).
case_images: Cortical lamination in Case 3.. Examination with several cortical layer markers (antibodies against proteins denoted in each panel) revealed normal cortical lamination in Case 3.
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case_images: However, cortical lamination, which we considered might have been affected by LHX1 deficiency, was normal when examined with several cortical layer markers (Figure 5).
case_images: Facial dysmorphism in Case 3.. (A) Dense surface morphology (DSM) results (See Text S1 for details). The scatter plot shows age (horizontally) against DSM distance (vertically) between the matched mean face and the patient and 200 control faces. Distance from the patient-matched mean face was linearly regressed against age for all controls. The patient was fitted to the appropriate regression and a 95% confidence interval was calculated for the predicted distance from the patient-matched mean. The scatter plot shows that Case 3 (square) is well outside the 95% confidence interval (bar). (B) Heat maps using a red-green-blue spectrum to depict inward-null-outward displacement along the surface normal for the patient face relative to its matched mean face using 50 control subjects. Displacement is expressed as the number of standard deviations (Stdv) from the mean. The lateral patches of red and yellow reflect an unusually narrow face. The red and yellow cheek patches and the null displaced green islands in the gonial region of the lower jaw reflect diminished fatty tissue rather than reduced gonial/skeletal width. Some fullness of the perioral region is shown (blue).
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case_images: Facial dysmorphism was confirmed by quantitative analysis in comparison with 200 age-, sex- and ethnicity-matched controls (Figure 6, Video S3).