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.

摘要 背景：性染色体三体（SCT）包括克氏（XXY）、XYY综合征和X三体（XXX），发生在1个 每500个新生儿。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。 紊乱在医学上，SCT与XXY的睾丸功能衰竭、XXX的卵巢功能衰竭相关，并且所有这些都增加了发病率 以及由于胰岛素抵抗、癫痫发作和其他健康状况的高风险而导致的死亡率。产前SCT诊断具有重要意义- 在过去的十年中，随着非侵入性产前筛查（NIPS）的普及，美国的这一比例有所上升。The extraordi- narY婴儿研究于2017年启动，招募了最大和最多样化的产前诊断SCT队列， 日期，包括271名婴儿，前瞻性随访2个月至3 - 4岁，详细的医疗，激素， 发育表型分析与包括超过1250份生物样本的纵向生物库相结合。结果表明， SCT中以前未描述的医学特征，发育里程碑的详细获取，以及确定的不同- 早期语言和行为特征的变化被认为是后来诊断的"危险信号"，如自闭症、阅读障碍和多动症。 父母分享了经验，强调需要改进遗传咨询模式。 对受试者进行学龄期随访至关重要，因为重要的合并症，如阅读障碍， 注意力缺陷多动障碍，自闭症和内分泌功能障碍正在出现，表型变异扩大，发育和健康 结果变得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 神经发育的自然史，SCT的医学问题和激素概况，通过对eX- （2）确定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;（3） 开发一个基于证据的，父母知情的产前遗传咨询的最佳实践模式， SCT人口。 方法：当前研究受试者（n = 262; XXY = 174，XYY = 25，XXX = 54，XXYY/XXXY = 9）和60名新招募的儿童将 完成7 - 8岁的年度评估。新的招聘将针对那些代表性不足的种族和 种族群体、低社会经济地位、农村地区以及XYY和XXX。人口统计学、健康和家族史，以及 将收集教育/干预措施，沿着评估：（1）认知、心理和运动功能;（2） 身体和性腺的措施和（3）生活质量。统计模型将对比每个SCT组的纵向特征 并与人口标准进行比较。将使用线性模型和逻辑回归来检验潜在风险之间的关联。 7岁时的早期危险因素和选定结果。将生物样品加入生物储存库。家长体验- 产前SCT诊断的病例将通过混合方法进行分析，以开发基于证据的遗传学方法。 咨询资源。影响：对产前确定的SCT儿童的最大队列的纵向研究提供了一个 新的资源，将告知SCT的发育和医学概况的自然史，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标本库 以供将来研究。

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