Prenatal Microarray Follow-Up Study

Study Overview
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Brief Summary
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The objectives of this multi-center collaborative study are to ascertain the frequency of specific copy number variants (CNVs) identified prenatally and to evaluate in detail through continued follow-up of the children the phenotypes associated with CNVs of known or uncertain clinical significance.

Detailed Description
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Specifically the aims are as follows: Determine the intellectual function of the children at age 3 years Determine phenotypic characteristics other than intellectual function of the children at age 3 years Determine the frequency of specific copy number variants discovered during routine prenatal diagnostic testing Evaluate the educational, counseling and psychosocial implications of microarray testing as it is introduced as a standard prenatal diagnostic procedure.

Official Title
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Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis: Follow-Up

Conditions
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Genetic Diseases

Intervention / Treatment
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* Other: 3-year follow-up


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria for Enrollment into the 3 year Follow-up Cohort Inclusion Criteria Singleton or multi-fetal pregnancy with a prenatal invasive procedure resulting in a diagnosis by microarray analysis of a microdeletion/duplication less than 10 Mbs, either pathogenic or of uncertain significance, which is reported to the patient. This includes: Infants diagnosed during prenatal diagnostic studies performed at the10 pre-specified prenatal diagnostic centers Infants diagnosed by analysis of microarrays performed at the collaborating laboratories Infants referred through the Prenatal Microarray Resource Center website Children who will be at least 3 years of age by January of 2018, and who had a prenatally detected CNV <10 Mbs, either pathogenic or of uncertain significance OR Children whose mothers were enrolled in the initial study (through July 2011) and who met inclusion criteria for follow-up in that phase, referred to as the Index cohort. This includes: CNVs of uncertain or known significance, some of which were not reported to the patient Mosaic findings by karyotype and/or microarray alone. Exclusion Criteria Patient refusal to allow infant follow-up through the age of three Patient not fluent in the English language Patient under the age of 18 In surrogate pregnancies, the rearing parents are unavailable to give consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 3 year follow-up cohort<br>When the infants reach 24 months of age, the Study Follow-up Specialist will send all participants an age- appropriate Ages and Stages Questionnaire (ASQ) for completion. At as close to the age of 3 as possible, the following exams will be performed and are described below: The Vineland-II Adaptive Behavior Scale (VABS) Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV), or Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V, for siblings older than 7 years 7 months, when necessary) Children will also be photographed (for review by the study dysmorphologist) | Other: 3-year follow-up<br>* When the infants reach 24 months of age, the Study Follow-up Specialist will send all participants an age- appropriate Ages and Stages Questionnaire (ASQ) for completion. At the age of 3, the following exams will be performed and are described below: The Vineland-II Adaptive Behavior Scale (VABS) Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV), or Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V, for siblings older than 7 years 7 months, when necessary) Children will also be photographed (for review by the study dysmorphologist)<br>|
| Limited follow-up cohort<br>Women with children who will not reach the age of 2 years 6 months by the end of our study but have a prenatally diagnosed CNV will be recruited into the limited follow-up study. Each center will describe the study to eligible women and will verbally obtain their permission to be contacted by the Study Follow-up Specialist. The Study Follow-Up Specialist will contact the patient, explain the study, and obtain full written informed consent. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Full Scale Intelligence Quotient (IQ) score | Full Scale IQ score from the Wechsler Preschool and Primary Scale of Intelligence IV or Wechsler Intelligence Scale for Children 5th edition | age 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects with specific commonly occurring CNVs |  | detected prenatally | 
| Percent of subjects with seizure disorders |  | age: up to 3 years | 
| Percent of subjects with cerebral palsy |  | age: up to 3 years | 
| Percent of subjects with dysmorphic features diagnosed by dysmorphologist |  | age 3 years | 
| Percent of subjects with structural anomalies |  | age: up to 3 years | 
| Verbal Comprehension composite score | Verbal Comprehension composite score from the Wechsler Preschool and Primary Scale of Intelligence IV | age: up to 3 years | 
| Visual Spatial composite score | Visual Spatial composite score from the Wechsler Preschool and Primary Scale of Intelligence IV | age: up to 3 years | 
| Working Memory composite score | Working Memory composite score from the Wechsler Preschool and Primary Scale of Intelligence IV | age: up to 3 years | 
| Communication domain score | Communication domain score from the Vineland Adaptive Behavior Scale | age: up to 3 years | 
| Daily Living Skills domain score | Daily Living Skills domain score from the Vineland Adaptive Behavior Scale | age: up to 3 years | 
| Socialization domain score | Socialization domain score from the Vineland Adaptive Behavior Scale | age: up to 3 years | 
| Motor Skills domain score | Motor Skills domain score from the Vineland Adaptive Behavior Scale | age: up to 3 years | 
| Adaptive Behavior Composite score | Adaptive Behavior Composite score from the Vineland Adaptive Behavior Scale | age: up to 3 years | 
| Age-adjusted Z scores for birth weight |  | birth | 
| Age-adjusted Z scores for birth length |  | birth | 
| Age-adjusted Z scores for head circumference |  | birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microarray, prenatal, copy number variant, CNV, microdeletion, microduplication, genetic