Abnormal Brain Structure in Children With Isolated Clefts of the Lip or Palate

OBJECTIVE: To evaluate brain structure in a sample of children with isolated clefts of the lip and/or palate (ICLP). DESIGN: Case-control study. SETTING: Tertiary care center. PARTICIPANTS: A large sample of 74 children aged 7 to 17 years with ICLP was compared with a healthy control group, matched by age and sex. MAIN EXPOSURE: Isolated cleft lip and/or palate. OUTCOME MEASURES: General measures of height and head circumference were obtained. Brain structure was evaluated using magnetic resonance imaging, generating both general and regional brain measures (volumes). RESULTS: Height was significantly lower in the ICLP group (F = 4.83, P = .03). After controlling for this smaller body size, children with ICLP had abnormally small brains with both cerebrum (F = 4.47, P = .04) and cerebellum (F = 14.56, P <.001) volumes substantially decreased. Within the cerebrum, the frontal lobe was preferentially decreased (F = 7.22, P = .008) and subcortical nuclei were also substantially smaller (F = 4.18, P = .003). Tissue distribution of cortical gray matter and white matter within the cerebrum were abnormal in boys with ICLP (larger cortical volume, smaller volume of white matter) but proportional to controls in girls with ICLP. CONCLUSIONS: Children with ICLP have abnormal brain structure, potentially due to abnormal brain development. The fact that the pattern of brain abnormalities in children with ICLP is dramatically different from the pattern of brain abnormalities seen in adults with ICLP suggests that brain growth and development trajectory is also abnormal in subjects with ICLP.