This study is designed to evaluate brain structure and function in children with non-syndromic clefts of the lip and/or palate (NSCLP). In addition, the study will evaluate the relationship between measures of brain structure/function and genes associated with oral clefts. The etiology of non-syndromic oral clefts is complex, involving both genetic and environmental factors. Cognitive dysfunction is frequently associated with oral clefts. In syndromic clefting disorders, cognitive dysfunction is ubiquitous and often severe (mental retardation). The cognitive dysfunction associated with non-syndromic clefts is less severe but should not be underestimated. The fact that clefts of the lip and/or palate are associated with structural brain abnormalities is intuitive as the development of the brain and face are intimately related. However, the systematic study of the types of brain anomalies present in patients with clefts of the lip and/or palate (and the functional consequences thereof) has been almost completely overlooked. In the first study of its kind, the principal investigator of this grant has evaluated brain structure and function using Magnetic Resonance Imaging (MRI) in a group of adult males with NSCLP. The findings from that study indicate a pattern of cognitive dysfunction involving language and executive functions. In addition, there were robust abnormalities in volume and tissue composition of the cerebrum and cerebellum. Moreover, the abnormalities in brain structure were directly related to the abnormalities in cognitive function. Several studies have documented the cognitive dysfunction of children with NSCLP. Findings include global mild deficits with specific problems with language function. Although it has been hypothesized that these abnormalities are due to a primary problem in brain structure and function, no study to date has evaluated brain structure in this population. Evaluating brain structure in this group and its relationship to brain function will be key information to the search for understanding the neurobiology of cognitive dysfunction in this group. In addition, several genes have been associated with non-syndromic oral clefting and may play a key role in its pathoetiology (e.g. MSX1, TGFB3, TGFA). It is likely that the genetic determinants of non-syndromic clefting are related to the accompanying abnormalities in brain structure and function. Evaluating the relationship between brain structure/function and genes known to be associated with non-syndromic clefts may shed light on possible etiologic mechanisms at the molecular level.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Riddle, Melissa
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University of Iowa
Schools of Medicine
Iowa City
United States
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Goodwin, Jon W; Conrad, Amy L; Ansley, Timothy et al. (2017) Arithmetical calculation and related neuropsychological skills in subjects with isolated oral clefts. Neuropsychology 31:834-841
Conrad, Amy L; Goodwin, Jon W; Choi, James et al. (2017) The Relationship of Exposure to Anesthesia on Outcomes in Children With Isolated Oral Clefts. J Child Neurol 32:308-315
Conrad, Amy L; McCoy, Thomasin E; DeVolder, Ian et al. (2014) Reading in subjects with an oral cleft: speech, hearing and neuropsychological skills. Neuropsychology 28:415-22
Chollet, Madeleine B; DeLeon, Valerie B; Conrad, Amy L et al. (2014) Morphometric analysis of brain shape in children with nonsyndromic cleft lip and/or palate. J Child Neurol 29:1616-25
Belfi, Amy M; Conrad, Amy L; Dawson, Jeffrey et al. (2014) Masculinity/femininity predicts brain volumes in normal healthy children. Dev Neuropsychol 39:25-36
Chollet, Madeleine B; Aldridge, Kristina; Pangborn, Nicole et al. (2014) Landmarking the brain for geometric morphometric analysis: an error study. PLoS One 9:e86005
DeVolder, Ian; Richman, Lynn; Conrad, Amy L et al. (2013) Abnormal cerebellar structure is dependent on phenotype of isolated cleft of the lip and/or palate. Cerebellum 12:236-44
van der Plas, Ellen; Koscik, Timothy R; Conrad, Amy L et al. (2013) Social motivation in individuals with isolated cleft lip and palate. J Clin Exp Neuropsychol 35:489-500
van der Plas, Ellen; Caspell, Chelsea J; Aerts, Andrea M et al. (2012) Height, BMI, and pituitary volume in individuals with and without isolated cleft lip and/or palate. Pediatr Res 71:612-8
Richman, Lynn C; McCoy, Thomasin E; Conrad, Amy L et al. (2012) Neuropsychological, behavioral, and academic sequelae of cleft: early developmental, school age, and adolescent/young adult outcomes. Cleft Palate Craniofac J 49:387-96

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