2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-NIPS dilemma in the context of consanguinity; considerations for counseling

Pdf Summary

The document discusses the dilemma faced in noninvasive prenatal screening (NIPS) for detection of fetal aneuploidy in the context of consanguinity. NIPS is a widely used method to identify chromosomal abnormalities in fetuses, but it may yield atypical results in cases of consanguinity. Atypical results can be caused by factors such as parental consanguinity, fetal or placental mosaicism, or sex chromosome anomalies.<br /><br />The case presented in the document involves a patient with an atypical NIPS result. The NIPS test predicted a female fetus but did not provide a result for sex chromosome abnormalities, suggesting a suspected fetal origin. A subsequent chromosomal microarray analysis (CMA) revealed a normal female karyotype but identified regions of homozygosity (ROHs), indicating consanguinity. The laboratory performing the CMA did not report on ROH on chromosome X due to high sequence homology.<br /><br />The document emphasizes the importance of informed decision-making and counseling when consanguinity is a possible contributor to an atypical NIPS result. Clinicians need to carefully consider test selection and provide risk assessments for families who wish to avoid diagnostic testing. In cases where diagnostic testing is chosen, clinicians should consider the use of massive parallel shotgun sequencing NIPS. It is also important to note that not all reported ROHs definitively indicate a specific familial relationship.<br /><br />The document cites various studies that highlight the impact of consanguinity on NIPS results and provide insights into managing such cases. The clinical utility and expansion of NIPS and CMA have been valuable in prenatal genetics, but the presence of unconventional nuances requires clinicians to be knowledgeable about test limitations and provide appropriate counseling.<br /><br />In summary, the document emphasizes the considerations and challenges faced in NIPS testing when consanguinity is involved. It highlights the need for careful judgment, test selection, and counseling to provide accurate information and support for families in making informed decisions.

Asset Subtitle

Presenting Author - Noura Osman, MSc; Co-Author - Kathryn Rice, MSc; Co-Author - Herman L. Hedriana, MD; Co-Author - Krishna R. Singh, MD, FACMG, FACOG;

Meta Tag

array CGH

Cell free DNA/cfDNA

Chromosomal Abnormalities

Counseling

Education

Genetic Testing

Genomic Methodologies

Population Genetics

Co-Author Kathryn Rice, MSc

Co-Author Herman L. Hedriana, MD

Co-Author Krishna R. Singh, MD, FACMG, FACOG

Presenting Author Noura Osman, MSc

Keywords

noninvasive prenatal screening

NIPS

fetal aneuploidy

consanguinity

chromosomal abnormalities

atypical results

parental consanguinity

fetal mosaicism

placental mosaicism

sex chromosome anomalies