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

• 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
• 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' 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

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 名新生儿中。在儿童时期，语言和学习障碍、多动症、自闭症和情绪障碍的风险增加 失调。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死亡。产前 SCT 诊断已取得重大进展 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。非凡的 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。结果已确定 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，发育和健康状况恶化 结果更能预测以后的功能。在这个更新项目中，我们的目标是： (1) 描述和比较 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 的激素特征 进入学龄早期的异常婴儿队列，(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 7-8 岁之前完成年度评估。新的招聘将针对那些来自代表性不足的种族和群体的人 种族群体、社会经济地位低下、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) 身体和性腺指标以及 (3) 生活质量。统计模型将对比每个 SCT 组的纵向概况 并与人口标准进行比较。线性模型和逻辑回归将用于测试潜在之间的关联 早期危险因素和 7 岁时选定的结果。生物样本将添加到生物样本库中。家长体验 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 咨询资源。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

'I Wish the School Had a Better Understanding of the Diagnosis': parent perspectives on educational needs of students with sex chromosome aneuploidies.

• DOI: 10.1111/1471-3802.12558
• 发表时间: 2022-04
• 期刊: JOURNAL OF RESEARCH IN SPECIAL EDUCATIONAL NEEDS
• 影响因子: 1.5
• 作者: Thompson, Talia;Stinnett, Nicole;Tartaglia, Nicole;Davis, Shanlee;Janusz, Jennifer
• 通讯作者: Janusz, Jennifer

Early symptoms of autism spectrum disorder (ASD) in 1-8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention.

• DOI: 10.1007/s00787-022-02070-y
• 发表时间: 2023-11
• 期刊: EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
• 影响因子: 6.4
• 作者: Bouw, Nienke;Swaab, Hanna;Tartaglia, Nicole;Wilson, Rebecca L.;Van der Velde, Kim;van Rijn, Sophie
• 通讯作者: van Rijn, Sophie

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: 10.1002/jgc4.1639
• 发表时间: 2023
• 期刊: Journal of genetic counseling
• 影响因子: 1.9
• 作者: Howell,Susan;Davis,ShanleeM;Thompson,Talia;Brown,Mariah;Tanda,Tanea;Kowal,Karen;Alston,Amanda;Ross,Judith;Tartaglia,NicoleR
• 通讯作者: Tartaglia,NicoleR

Early developmental impact of sex chromosome trisomies on attention deficit-hyperactivity disorder symptomology in young children.

• DOI: 10.1002/ajmg.a.62418
• 发表时间: 2021-12
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
• 影响因子: 2
• 作者: Kuiper, Kimberly;Swaab, Hanna;Tartaglia, Nicole;van Rijn, Sophie
• 通讯作者: van Rijn, Sophie

Current survey of early childhood intervention services in infants and young children with sex chromosome aneuploidies.

性染色体非整倍体婴幼儿早期干预服务现状调查。

• DOI: 10.1002/ajmg.c.31785
• 发表时间: 2020
• 期刊: American journal of medical genetics. Part C, Seminars in medical genetics
• 作者: Thompson,Talia;Howell,Susan;Davis,Shanlee;Wilson,Rebecca;Janusz,Jennifer;Boada,Richard;Pyle,Laura;Tartaglia,Nicole
• 通讯作者: Tartaglia,Nicole