Relationship between genotype and arcuate fasciculus morphology in six young children with global developmental...

To investigate whether different genetic mutations observed in children with global developmental delay (GD) are associated with unique patterns of the arcuate fasciculus dysmorphology.

Six children with GD (age: 36.8 ± 14.1 months, 5 boys) having mutations in MID1, CDK4, SFRP1, EN2, RXRG-GLRB, or MECP2, and five children with typical development (TD, age: 38.5 ± 20.5 months, 4 boys) underwent a 3 Tesla MRI including diffusion weighted imaging (DWI). Five language pathway segments in the left hemisphere, "C₁ : Broca's to Wernicke's area," "C₂ : Broca's to premotor area," "C₃ : premotor to Wernicke's area," "C₄ : Wernicke's to inferior parietal area," and "C₅ : premotor to inferior parietal area" were objectively identified using the DWI "maximum a posteriori probability" classifier.

Affinity propagation clustering analysis found that three arcuate pathway segments, C_1,2,4 , of MID1, CDK4, EN2, and MECP2 had a similar pattern of volume ratio while those of SFRP1 and RXRG-GLRB had a heterogeneous pattern of volume ratio (net similarity = -0.01). Using receiver operating characteristic curve analysis, the fiber ratios of C_1,2,4 showed a high probability to discriminate between GD and TD, yielding an accuracy of 0.91, 0.91, 1.00, respectively. The fiber volumes of C₁ and C₄ showed a strong correlation with expressive language (R²  = 0.6019; P-value = 0.033) and receptive language (R²  = 0.6379; P-value = 0.028), respectively.

The findings of the present study provide preliminary evidence to suggest that different segments of the arcuate fasciculus are formed under the regulation of different genes which, when mutated, may result in developmental delay. J. Magn. Reson. Imaging 2016;44:1504-1512.