Advancing fetal diagnosis and prognostication using comprehensive prenatal phenotyping and genetic testing

Area of Science:

• Medical Genetics
• Prenatal Diagnosis
• Reproductive Medicine

Background:

• High-resolution prenatal imaging has increased congenital malformation diagnoses, yet outcomes vary widely, complicating parental discussions.
• Comprehensive prenatal genetic testing is crucial for accurate prognostication and informed decision-making.
• Genetic testing strategies include chromosomal microarray, exome sequencing, and genome sequencing, with diagnostic yield dependent on malformation specifics.

Purpose of the Study:

• To review available prenatal genetic testing options.
• To discuss the impact of prenatal genetic testing on clinical care and family decision-making.
• To consolidate current literature on the diagnostic yield of genetic testing for prenatal diagnosis of congenital malformations.

Main Methods:

• Review of current literature on prenatal genetic testing strategies.
• Analysis of diagnostic yield based on malformation type, severity, and organ involvement.
• Examination of the utility and challenges of prenatal genetic diagnosis, including turnaround time and result uncertainty.

Main Results:

• Prenatal genetic testing enhances diagnostic clarity for clinicians and families.
• It supports informed pregnancy and neonatal care planning.
• Challenges include test turnaround time and inherent result uncertainty, necessitating genetic counseling.

Conclusions:

• Prenatal genetic testing is essential for diagnosing congenital malformations and guiding pregnancy decisions.
• Genetic counseling is vital for understanding results and making informed choices.
• Further evaluation of exome/genome sequencing in structurally normal fetuses is needed, considering ethical implications.