Health outcomes and improved phenotypic characterization of cleft lip and palate

描述（由申请人提供）： 唇裂和/或腭裂（CLP）是一种常见的出生缺陷，发生率约为1/500至1/2500。 大多数病例为非综合征型（NS），没有其他重大出生缺陷或综合征，但NS CLP形式对受影响的个人和家庭造成了巨大的健康负担。 早期生活并发症包括喂养问题和复发性耳部感染，某些慢性疾病（如癌症、精神健康状况和死亡率）以及不良社会经济后果的长期风险也可能增加。 预计直系亲属的健康、社会和经济成果也可能受到不利影响。 然而，由于缺乏适当和大规模的数据来源来跟踪案例和衡量结果，关于CLP的长期结果仍有很多东西有待了解。 关于CLP产前诊断对受影响儿童及其家庭成员健康结果的净影响也知之甚少，CLP越来越普遍。 改善CLP的表型表征是另一个优先研究领域，也为改善复发风险的估计和受影响家庭的咨询提供了真实的前景，增加了遗传和基因-环境相互作用研究的力量，并为不良健康和心理社会后果的风险早期预测。 建议的研究针对这些优先领域，这些领域代表中电在RFA中的优先领域B，e，f，g，h。将使用丹麦独特的人口登记系统评价NS CLP对受影响个体及其一级亲属的长期健康、医疗保健利用和社会经济结局的影响，该系统允许通过丹麦整个人口的个人水平数据的几个健康和社会人口统计学登记系统跟踪1936年开始出生的约8300例NS CLP病例及其一级亲属。 代表丹麦人口5%的随机样本将与他们的一级亲属作为对照组。 该研究还将测量1996年至2007年期间在爱荷华州出生的NS CLP病例中选定的亚表型，包括口轮匝肌（OO）不连续、咽闭合不全（VPI）、唇涡、偏侧和颅面畸形，这些病例通过爱荷华州的出生缺陷登记处和他们的一级亲属以及未受影响的对照确定。 亚表型信息将用于复发风险估计，也将与心理社会结局相关。 将获得DNA样本用于利用亚表型信息的基因-环境病因学研究。 这项研究还将评估产前诊断对来自爱荷华州的样本中儿童和家庭结局的影响，并测量父母对产前诊断的偏好。 这项研究提供了一个真实的机会，增加重要的科学知识，可以直接转化为改善受影响的个人和家庭的结果，并可能增加制定预防战略的机会。该项目旨在评估唇腭裂的长期健康结果，并确定可能与这种负担和常见的出生缺陷有关的特征和特点。 研究结果对于确定医疗保健需求，改善护理实践和制定预防唇腭裂和/或减少其相关不良影响的策略具有高度相关性。

DESCRIPTION (provided by applicant): 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.