SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
Condition: 22q11 Deletion Syndrome; DiGeorge Syndrome; Trisomy 21; Trisomy 18; Trisomy 13; Monosomy X; Sex Chromosome Abnormalities; Cri-du-Chat Syndrome; Angelman Syndrome; Prader-Willi Syndrome; 1p36 Deletion Syndrome
MeSH terms: DiGeorge Syndrome; 22q11 Deletion Syndrome; Prader-Willi Syndrome; Angelman Syndrome; Down Syndrome; Trisomy 13 Syndrome; Cri-du-Chat Syndrome; Trisomy 18 Syndrome; Chromosome Disorders; Syndrome; Aneuploidy; Trisomy; Chromosome Aberrations; Monosomy; Sex Chromosome Aberrations
Study type: Observational [Patient Registry]

Summary: 
      This multi-center prospective observational study is designed to track birth outcomes and
      perinatal correlates to the Panorama prenatal screening test in the general population among
      ten thousand women who present clinically and elect Panorama microdeletion and aneuploidy
      screening as part of their routine care. The primary objective is to evaluate the performance
      of Single Nucleotide Polymorphism (SNP)-based Non Invasive Prenatal Testing (NIPT) for
      22q11.2 microdeletion (DiGeorge syndrome) in this large cohort of pregnant women. This will
      be done by performing a review of perinatal medical records and obtaining biospecimens after
      birth to perform genetic diagnostic testing for 22q11.2 deletion. Results from the follow-up
      specimens will be compared to those obtained by the Panorama screening test to determine test
      performance. Specific test performance parameters will include: PPV, specificity, and
      sensitivity.
    

Detailed description: 
      The primary objective is to determine in a prospective study the performance of SNP based
      NIPT for the 22q11.2 microdeletion (DiGeorge syndrome) in a large cohort of pregnant women
      clinically opting for this form of screening. Specific test performance parameters will
      include: positive predictive value (PPV), specificity, and sensitivity.

      Secondary objectives include:

        1. Determine the test performance (PPV, specificity) of SNP based NIPT for detecting other
           microdeletion syndromes available in the Panorama microdeletion panel (e.g., 1p36
           deletion, Cri-du-chat, Prader-Willi, and Angelman) individually and all combined
           (including 22q11.2). Given the incidences of <1:5000, the confidence intervals are
           expected to be large.

        2. Determine the failure ('no call') rate for the Next-generation Aneuploidy Test Using
           SNPs (NATUS) method for 22q11.2 detection, as well as for aneuploidy.

        3. Determine whether a more precise risk for aneuploidy can be generated in the setting of
           low fetal fraction by incorporating maternal BMI (adjusted fetal fraction percentile).

        4. Assess whether low fetal fraction is associated with specific ultrasound findings that
           may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).

        5. Investigate the relationship between NIPT and sonographic (nuchal translucency and
           anatomy survey) markers and serum markers from 1st and 2nd trimester aneuploidy
           screening.

        6. Determine sensitivity, specificity, and PPV for chromosomal aneuploidies and sex
           chromosome abnormalities.

        7. Perform detailed assessment of false positive aneuploidy samples to better understand
           sources of error, including placental studies to further refine issues surrounding
           mosaicism as NIPT represents circulating placental DNA.

        8. Investigate any relationships between circulating placental DNA (fetal fraction) or
           other test parameters including potential genotypic markers, and outcomes related to
           abnormal placentation (including but not limited to preeclampsia, small for gestational
           age and morbidly adherent placenta).

        9. Investigate other risk factors that may impact risk assessment for microdeletions
           including sonographic findings consistent with 22q11.2 (cardiac anomalies and thymus
           size).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women
      
Biospecimen description: 
      -  Maternal residual blood sample

        -  Placental tissue

        -  Child dried blood spot

        -  Child buccal sample
    
Keywords: Microdeletion Syndrome; Aneuploidy; 22q; Non-Invasive Prenatal Screening; DiGeorge Syndrome