? Cleft lip and/or palate (CLP) is a common birth defect occurring in about 1/500 to 1/2500 births. The majority of cases are nonsyndromic (NS) without other major birth defects or syndromes but NS CLP forms impose substantial health burden on both affected individuals and families. Early life complications include feeding problems and recurrent ear infections and increased long term risks may also occur for certain chronic conditions such as cancer, mental health conditions and mortality and for adverse socioeconomic outcomes. It is also anticipated that the health, social and economic outcomes of immediate family members may also be adversely affected. Yet much remains to be learned about the long term outcomes of CLP primarily due to the lack of appropriate and large-scale data sources to track cases and measure outcomes. Little is also known about the net effects of prenatal diagnosis of CLP, which is becoming increasingly common, on the health outcomes of affected children and their family members. Improved phenotypic characterization of CLP represents another priority research area that also provides a real prospect for improving the estimation of recurrence risks and counseling of affected families, increasing the power of genetic and gene-environment interaction studies and for early prediction of risks for adverse health and psychosocial outcomes. ? The proposed study addresses these priority areas, which represent CLP priority areas b, e, f, g, h in the RFA. The effects of NS CLP on long term health, health care utilization, and socioeconomic outcomes of affected individuals and their first degree relatives will be evaluated using a unique population registry system in Denmark which allows tracking about 8300 cases with NS CLP born starting 1936 and their first degree relatives through several health and socio-demographic registries of individual-level data on the whole population of Denmark. A random sample representing 5% of the Danish population will be selected with their first degree relatives as comparison groups. The study will also measure selected subphenotypes including Orbicularis Oris (OO) discontinuity, velopharyngeal incompetence (VPI), lip whorls, laterality and craniofacial dysmorphology in cases born with NS CLP in Iowa between 1996 and 2007 and identified through Iowa's birth defects registry and their first degree relatives as well as unaffected controls. Subphenotypic information will be used for recurrence risk estimation and will also be correlated with psychosocial outcomes. DNA samples will be obtained for gene-environment etiology studies that make use of the subphenotypic information. The study will also assess the effects of prenatal diagnosis on child and family outcomes in the samples from Iowa and measure parental preferences towards prenatal diagnosis. The study provides a real opportunity for adding significant scientific knowledge that can be directly translated into improving the outcomes of affected individuals and families and that may increase the chances for developing prevention strategies.This project aims at evaluating the long term health outcomes of cleft lip and palate and at identifying traits and characteristics that may be associated with this burdensome and common birth defect. The study results are highly relevant for identifying health care needs, improving care practices and developing strategies to prevent cleft lip and palate and/or reduce its associated adverse effects. ? ? ? ? ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
Centers for Disease Control and Prevention (NCBDD)
Type
Research Project (R01)
Project #
1R01DD000295-01
Application #
7406142
Study Section
Special Emphasis Panel (ZCD1-AWI (07))
Program Officer
Irannejad, Nassi
Project Start
2007-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$454,175
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Zhang, Charles; Miller, Steven F; Roosenboom, Jasmien et al. (2018) Soft tissue nasal asymmetry as an indicator of orofacial cleft predisposition. Am J Med Genet A 176:1296-1303
Weinberg, Seth M; Leslie, Elizabeth J; Hecht, Jacqueline T et al. (2017) Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation. Cleft Palate Craniofac J 54:631-638
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Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R et al. (2017) Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate. Am J Med Genet A 173:1531-1538
Ruegg, Teresa A; Cooper, Margaret E; Leslie, Elizabeth J et al. (2017) Ear Infection in Isolated Cleft Lip: Etiological Implications. Cleft Palate Craniofac J 54:189-192
Hatch, Cory D; Wehby, George L; Nidey, Nichole L et al. (2017) Effects of Objective 3-Dimensional Measures of Facial Shape and Symmetry on Perceptions of Facial Attractiveness. J Oral Maxillofac Surg 75:1958-1970
Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R et al. (2017) Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate. Hum Genet 136:275-286
Weinberg, Seth M; Raffensperger, Zachary D; Kesterke, Matthew J et al. (2016) The 3D Facial Norms Database: Part 1. A Web-Based Craniofacial Anthropometric and Image Repository for the Clinical and Research Community. Cleft Palate Craniofac J 53:e185-e197

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