The eXtraordinarY Babies Study: Natural History of Health and Neurodevelopment in Infants with Sex Chromosome Trisomy

非凡婴儿研究：性染色体三体婴儿的健康和神经发育自然史

基本信息

批准号：
10660803
负责人：
Nicole Renee Tartaglia
金额：
$ 66.55万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-06 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10660803
关键词：
4 year old 7 year old 8 year old Address Age Age Months Age Years Attention Attention deficit hyperactivity disorder Behavior Biological Biological Markers Biological Specimen Banks Birth Blood Body Composition Caring Child Childhood Chromosome abnormality Clinic Clinical Cognitive Cohort Studies Common Data Element Congenital Abnormality Counseling Coupled Data Dental Development Developmental Delay Disorders Diagnosis Disease Dual-Energy X-Ray Absorptiometry Dyslexia Education Emotional disorder Endocrine Enrollment Environment Ethnic Population Eye Failure Family Fatty acid glycerol esters Functional disorder Funding Future Genetic Genetic Counseling Goals Gonadal Steroid Hormones Growth Guidelines Health Heart Abnormalities Hormonal Hormones Infant Insulin Resistance Intervention Intervention Trial Investigation Klinefelter&apos s Syndrome Language Development Language Disorders Learning Disabilities Length Life Linear Models Logistic Regressions Longitudinal Studies Measures Medical Medical Genetics Methods Modeling Morbidity - disease rate Motor Motor Skills Natural History Neonatal Screening Neurodevelopmental Problem Neuropsychology Newborn Infant Obesity Outcome Parents Participant Pathway interactions Phase Phenotype Population Prenatal Diagnosis Prenatal Genetic Counseling Prospective Studies Protocols documentation Quality of life Reading Disabilities Recording of previous events Resources Risk Risk Factors Sample Size Sampling School-Age Population Seizures Sex Chromosomes Shapes Site Social Development Socioeconomic Status Speech Statistical Models Stress Supplementation Syndrome Testing Testosterone Torticollis Trisomy Trisomy X syndrome Underrepresented Populations Urine Work XYY Karyotype autism spectrum disorder biobank cardiometabolism clinical care cohort comorbidity data repository data sharing demographics early childhood ethnic minority population evidence base experience feeding follow-up high risk improved infancy infant outcome interest literacy low socioeconomic status mortality neurodevelopment novel outcome prediction ovarian failure patient oriented penis premature prenatal prenatal testing prospective psychologic racial minority population racial population reading ability recruit risk selection rural area skills standardize measure stool sample visual tracking

项目摘要

ABSTRACT Background: Sex Chromosome Trisomies (SCT) including Klinefelter (XXY), XYY syndrome, and Trisomy X (XXX), occur in 1 out of every 500 births. In childhood there are increased risks for language and learning disabilities, ADHD, autism, and emotional disorders. Medically, SCTs are associated with testicular failure in XXY, ovarian failure in XXX, and all have increased morbidity and mortality due to high risks for insulin resistance, seizures, and other health conditions. Prenatal SCT diagnosis has dras- tically increased over the past decade in the US with more widespread noninvasive prenatal screening (NIPS). The eXtraordi- narY Babies Study was launched in 2017, and has enrolled the largest and most diverse prenatally diagnosed SCT cohort to date, including 271 infants followed prospectively from 2 months to 3-4 years of age with detailed medical, hormonal, and developmental phenotyping coupled with a longitudinal biobank including over 1250 biospecimens. Results have identified medical features not previously described in SCT, detailed acquisition of developmental milestones, and identified differ- ences in early speech and behavior profiles known to be ‘red flags’ of later diagnoses such as autism, dyslexia, and ADHD. Parents shared experiences highlighting the need for improved genetic counseling models. Follow-up of participants into the school-age years is critical as important comorbidities such as reading disabilities, ADHD, autism and endocrine dysfunction being to emerge, phenotypic variability broadens, and developmental and health outcomes become more predictive of later functioning. In this renewal project we aim to: (1) Describe and compare the natural history of neurodevelopment, medical problems and hormonal profiles of SCT through prospective study of the eX- traordinarY Babies cohort into early school age, (2) To identify of poor developmental and health outcomes in SCT, with special attention to modifiable factors of development, health and environment to guide future intervention trials, and (3) To develop an evidence-based, parent-informed best practice model for prenatal genetic counseling unique to the needs of the SCT population. Approach: Current study participants (n=262; XXY=174, XYY=25, XXX=54, XXYY/XXXY=9) and 60 newly recruited children will complete annual assessments up to 7-8 years of age. New recruitment will target those from underrepresented racial and ethnic groups, low socioeconomic status, rural locations, and XYY and XXX. Demographics, health and family history, and education/interventions will be collected, along with assessments of: (1) cognitive, psychological and motor functioning; (2) physical and gonadal measures and (3) quality of life. Statistical models will contrast longitudinal profiles for each SCT group and compare to population norms. Linear models and logistic regression will be used to test the association between poten- tial early risk factors and selected outcomes at age 7. Biological samples will be added to the biorepository. Parent experi- ences with the prenatal SCT diagnosis will be analyzed via a mixed method approach to develop evidence-based genetic counseling resources. Impact: Longitudinal study of the largest cohort of prenatally identified children with SCT provides a novel resource that will inform the natural history of developmental and medical profiles in SCTs, guide genetic counseling, identify targets for intervention trials, inform newborn screening, and provide an invaluable data and biospecimen repository for future research.

抽象的背景：性染色体三体 (SCT) 包括 Klinefelter (XXY)、XYY 综合征和 X 三体 (XXX)，发生率为 1 每 500 名婴儿中就有 1 人在儿童时期患语言和学习障碍、多动症、自闭症和情绪障碍的风险增加。从医学上来说，SCT 与 XXY 的睾丸衰竭、XXX 的卵巢衰竭有关，并且所有疾病的发病率都会增加。胰岛素抵抗、癫痫发作和其他健康状况的高风险导致的死亡率和死亡率已大大降低。过去十年来，随着无创产前筛查 (NIPS) 的广泛普及，美国的筛查率显着增加。 narY 婴儿研究于 2017 年启动，招募了规模最大、最多样化的产前诊断 SCT 队列日期，包括 271 名婴儿，对 2 个月至 3-4 岁的婴儿进行了前瞻性随访，并提供了详细的医疗、激素和发育表型分析与包含超过 1250 个生物样本的纵向生物库相结合，已确定结果。以前在 SCT 中未描述的医学特征、发育里程碑的详细获取以及确定的差异早期言语和行为特征中的缺陷被认为是后来诊断（如自闭症、阅读障碍和多动症）的“危险信号”。家长们分享了经验，强调需要改进遗传咨询模式。对参与者进行学龄期间的随访至关重要，因为阅读障碍、多动症、自闭症和内分泌功能障碍正在出现，表型变异性扩大，发育和健康在这个更新项目中，我们的目标是：（1）描述和比较结果。通过对 eX- 的前瞻性研究，了解神经发育的自然史、医疗问题和 SCT 的激素分布进入学龄早期的特殊婴儿队列，(2) 识别 SCT 中不良的发育和健康结果，特别关注发展、健康和环境的可改变因素，以指导未来的干预试验，以及（3）开发一种基于证据、家长知情的产前遗传咨询最佳实践模型，以满足儿童的独特需求 SCT 人群。方法：当前研究参与者（n=262；XXY=174，XYY=25，XXX=54，XXYY/XXXY=9）和 60 名新招募的儿童将完成年度评估，年龄不超过 7-8 岁。新招聘将针对代表性不足的种族和群体。种族群体、低社会经济地位、农村地区以及 XYY 和 XXX 人口统计、健康和家族史，以及将收集教育/干预措施以及以下方面的评估：(1) 认知、心理和运动功能；(2) 身体和性腺测量以及 (3) 生活质量统计模型将对比每个 SCT 组的纵向概况。并与总体常态进行比较，将使用线性模型和逻辑回归来测试潜力之间的关联。 7岁时的早期危险因素和选定的结果。生物样本将添加到生物样本库中。产前 SCT 诊断的相关性将通过混合方法进行分析，以开发基于证据的遗传影响：对产前确定的 SCT 儿童的最大队列进行的纵向研究提供了新颖的资源将告知 SCT 中发育和医学特征的自然史，指导遗传咨询，确定干预试验的目标，为新生儿筛查提供信息，并提供宝贵的数据和生物样本库以供将来的研究。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The emotional journey of adapting to prenatally identified trisomy X.

适应产前鉴定的 X 三体的情感旅程。

DOI：
发表时间：
2023-09-10
期刊：
影响因子：
0
作者：
Thompson, Talia;Tisher, Jessica;Davis, Shanlee;Miller, Christina;Kirk, Jillian;Tartaglia, Nicole;Howell, Susan
通讯作者：
Howell, Susan

The behavioral profile of children aged 1-5 years with sex chromosome trisomy (47,XXX, 47,XXY, 47,XYY).

1-5岁性染色体三体（47，XXX，47，XXY，47，XYY）儿童的行为特征。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Urbanus, Evelien;Swaab, Hanna;Tartaglia, Nicole;Cordeiro, Lisa;van Rijn, Sophie
通讯作者：
van Rijn, Sophie

New developments and future trajectories in supernumerary sex chromosome abnormalities: a summary of the 2022 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and XYY.

多余性染色体异常的新进展和未来轨迹：2022 年第三届克兰费尔特综合征、X 三体和 XYY 国际研讨会摘要。

DOI：
发表时间：
2023-03-01
期刊：
影响因子：
2.9
作者：
Gravholt, Claus H;Ferlin, Alberto;Gromoll, Joerg;Juul, Anders;Raznahan, Armin;van Rijn, Sophie;Rogol, Alan D;Skakkebæk, Anne;Tartaglia, Nicole;Swaab, Hanna
通讯作者：
Swaab, Hanna

Adaptive functioning in children and adolescents with Trisomy X: An exploratory analysis.

X 三体儿童和青少年的适应性功能：探索性分析。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Wigby, Kristen;Cordeiro, Lisa;Wilson, Rebecca;Angkustsiri, Kathleen;Simon, Tony J;Tartaglia, Nicole
通讯作者：
Tartaglia, Nicole

Noninvasive prenatal screening (NIPS) results for participants of the eXtraordinarY babies study: Screening, counseling, diagnosis, and discordance.

非凡婴儿研究参与者的无创产前筛查 (NIPS) 结果：筛查、咨询、诊断和不一致。

DOI：
发表时间：
2023-02
期刊：
影响因子：
0
作者：
Howell, Susan;Davis, Shanlee M;Thompson, Talia;Brown, Mariah;Tanda, Tanea;Kowal, Karen;Alston, Amanda;Ross, Judith;Tartaglia, Nicole R
通讯作者：
Tartaglia, Nicole R