Morphometric Analysis of Corpus Callosum Shape in Isolated Cleft Lip/Palate

Objective: Individuals with isolated cleft lip with or without cleft palate (CL/P) have been shown previously to have an increased frequency of midline brain abnormalities compared with healthy controls.  Additionally, a recent landmark-based morphometric analysis of the CL/P brain revealed gross alterations in shape, including changes in the corpus callosum (CC) and several other midline structures.  Because many of these morphological brain changes appear to correlate with degree of cognitive impairment in CL/P, the goal of the present study was to carry our more detailed assessment of CC shape and its potential cognitive consequences.

Method: Midline 2D brain images were obtained from previously collected T1 MRI scans of 24 adult male CL/P subjects and 40 adult male controls.  All subjects were right-handed.  Eight landmarks on the corpus callosum were collected from each scan and the x.y coordinate locations saved.  Procrustes superimposition analysis was performed on the landmark coordinate data followed by discriminant function analysis.  The relationship between CC shape and cognitive performance was explored with nonparametric correlation coefficients.

Result: Discriminant analysis revealed significant CC shape differences between CL/P cases and controls (p < 0.0001).  The most prominent shape difference involved an increase in overall convexity resulting from a superior displacement of the CC body coupled with anterior displacement of the splenium.  Within CL/P cases, increased dysmorphic CC shape was significantly correlated with reduced IQ, reduced verbal fluency, and poorer performance on complex figure tests (p < 0.05).

Conclusion: CL/P cases demonstrated significant CC shape differences compared with healthy controls, providing additional evidence that midline brain changes are part of the orofacial cleft phenotype.  These changes were correlated with selected measures of cognitive performance in a predictable fashion.