Regional Brain Morphometric Characteristics of Nonsyndromic Cleft Lip and Palate

Abstract

Nonsyndromic cleft lip and palate (NSCLP) encompasses a group of orofacial abnormalities. Emerging evidence has revealed the presence of structural brain abnormalities in affected individuals. Previous studies have performed structure-based volumetric analysis of the brain assessing gross lobular subdivisions of the cerebral cortex and white matter which may have only vague relationships to the functional subregions implicated in behavioral and cognitive deficits observed in NSCLP patients. High-resolution magnetic resonance imaging structural data were acquired to provide a detailed characterization of the brain with respect to both regional cortical volume and thickness in 26 children with NSCLP and 26 age- and demographically matched typically developing children. Children with NSCLP exhibited abnormally large cerebral cortex grey matter volumes with decreased volumes of subcortical grey matter and cerebral white matter structures. Hemisphere-specific patterns of cortical volume and thickness abnormalities were identified. This study is the first to examine cortical thickness abnormalities in NSCLP. Overall, these findings suggest that the brains of children with NSCLP are less mature than those of their age-matched peers. Gender-specific comparisons reveal that NSCLP females were more immature compared to their typically developing peers compared to NSCLP males.

Increased Risk for Neurodevelopmental Disorders in Children With Orofacial Clefts

“…31 Interestingly, associations between nonsyndromic OFC and structural brain anomalies have been reported in children and adolescents with clefts. 32,33 These midline brain anomalies have been associated with intellectual disability, developmental delay, and schizophrenia in previous studies. 34,35 The relatively high incidence of central nervous system abnormalities among individuals with nonsyndromic OFC, being approximately 13 times higher compared to that in the general population, 36 provides additional support for the hypothesis that cognitive and language deficits as well as other psychiatric disorders may be the result of underlying neurodevelopmental abnormalities.…”

Common basis for orofacial clefting and cortical interneuronopathy

“…An emerging alternative hypothesis holds that OFC-associated adverse neurobehavioral outcomes stem from primary neuroanatomical abnormalities related to cleft pathogenesis itself. In addition to the well-described interdependence of face and brain development 18 , this hypothesis is supported by recent neuroimaging studies documenting subtle and partially overlapping structural brain anomalies in patients born with OFCs 19 – 23 , in fetal mice with OFCs 24 , and adult mice with OFC-associated mutations 25 .…”

Articulation rehabilitation induces cortical plasticity in adults with non-syndromic cleft lip and palate

“…Compared with control (PoCG; P<0.001, uncorrected) and aNSCLP groups (P<0.05, cluster-level FWEcorrected), the bNSCLP group had an increased GMV in left postcentral gyrus. A previous study has demonstrated increased GMV in bilateral PoCG in children with NSCLP [ 8 ], indicating that this is an important region in the NSCLP cohorts. A previous analysis of stuttering adults has found increased GMV in the precentral and postcentral gyrus, inferior parietal, and temporal lobule of bilateral hemisphere, which might represent a long-term functional compensation for the cerebella and medulla function deficiency [ 29 ].…”

“…Brain morphological analyses of NSCL/P adults have indicated brain changes, such as increased frontal lobe volumes, decreased temporal and occipital lobe volumes, lower cerebellum volumes, and higher rates of cavum septum pellucidum compared with normal controls [ 11 – 14 ]. A pediatric NSCL/P study has found that compared with age-matched controls, children with NSCL/P (6 to 14 years of age) have increased global cortical gray matter volumes (GMV) with decreased volumes of subcortical grey matter and cerebral white matter structures [ 8 ]. Besides, they have increased cortical thickness (CT) in left frontal and right parietal lobes and decreased CT in right superior frontal cortex [ 8 ].…”

“…A pediatric NSCL/P study has found that compared with age-matched controls, children with NSCL/P (6 to 14 years of age) have increased global cortical gray matter volumes (GMV) with decreased volumes of subcortical grey matter and cerebral white matter structures [ 8 ]. Besides, they have increased cortical thickness (CT) in left frontal and right parietal lobes and decreased CT in right superior frontal cortex [ 8 ]. However, to our knowledge, it is not known whether AR might affect the brain morphological changes.…”