Genetic Diseases
Conditions
Keywords
microarray, prenatal, copy number variant, CNV, microdeletion, microduplication, genetic
Brief summary
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
Specifically the aims are as follows: 1. Determine the intellectual function of the children at age 3 years 2. Determine phenotypic characteristics other than intellectual function of the children at age 3 years 3. Determine the frequency of specific copy number variants discovered during routine prenatal diagnostic testing 4. Evaluate the educational, counseling and psychosocial implications of microarray testing as it is introduced as a standard prenatal diagnostic procedure.
Interventions
OTHER3-year follow-up
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)
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Human Genome Research Institute (NHGRI)
Columbia University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria for Enrollment into the 3 year Follow-up Cohort Inclusion Criteria 1. 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 2. 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
1. Patient refusal to allow infant follow-up through the age of three 2. Patient not fluent in the English language 3. Patient under the age of 18 4. In surrogate pregnancies, the rearing parents are unavailable to give consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Full Scale Intelligence Quotient (IQ) score | age 3 years | Full Scale IQ score from the Wechsler Preschool and Primary Scale of Intelligence IV or Wechsler Intelligence Scale for Children 5th edition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | age: up to 3 years | Verbal Comprehension composite score from the Wechsler Preschool and Primary Scale of Intelligence IV |
| Visual Spatial composite score | age: up to 3 years | Visual Spatial composite score from the Wechsler Preschool and Primary Scale of Intelligence IV |
| Working Memory composite score | age: up to 3 years | Working Memory composite score from the Wechsler Preschool and Primary Scale of Intelligence IV |
| Percent of subjects with specific commonly occurring CNVs | detected prenatally | — |
| Daily Living Skills domain score | age: up to 3 years | Daily Living Skills domain score from the Vineland Adaptive Behavior Scale |
| Socialization domain score | age: up to 3 years | Socialization domain score from the Vineland Adaptive Behavior Scale |
| Motor Skills domain score | age: up to 3 years | Motor Skills domain score from the Vineland Adaptive Behavior Scale |
| Adaptive Behavior Composite score | age: up to 3 years | Adaptive Behavior Composite score from the Vineland Adaptive Behavior Scale |
| Age-adjusted Z scores for birth weight | birth | — |
| Age-adjusted Z scores for birth length | birth | — |
| Age-adjusted Z scores for head circumference | birth | — |
| Communication domain score | age: up to 3 years | Communication domain score from the Vineland Adaptive Behavior Scale |
Countries
United States
Outcome results
None listed