Fetal cardiac abnormalities: Genetic etiologies to be considered

Abstract

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.

Intrauterine phenotype features of fetuses with Williams–Beuren syndrome and literature review

“…The most frequent CNV associated with cardiovascular abnormalities is deletion of chromosome 22q11.2. The most common cardiac defects of fetuses with 22q11.2 deletion syndrome are conotruncal defects, especially in interrupted aortic arch type B and in tetralogy of Fallot (Petracchi, Sisterna, Igarzabal, & Wilkins‐Haug, ; Schindewolf, Khalek, Johnson, Gebb, & Moldenhauer, ). The most common single‐gene disorder contributing to cardiac anomalies is Noonan syndrome (NS).…”

Ultrasound examination: The key to maximising the benefits of advances in molecular diagnostic technologies

“…This is highlighted in the review by Petracchi who advocates the use of whole exome sequencing (WES), as the prenatal appearance of a genetic syndrome may not always be concordant with the postnatal features we recognise, making a targeted approach to diagnosis with gene panels less useful as associations between fetal phenotypes and genetic changes continue to emerge. 21 Gray and colleagues expand on this and show how fetal phenotype-genotype correlations can be broad and disparate from the paediatric presentations we recognise. They emphasise the need for detailed prenatal imaging with documentation and communication of these prenatal findings to help our understanding of fetal development and the prenatal presentation of genetic conditions.…”

“…They suggest a structured approach to diagnosis. As with other systems, the multidisciplinary approach and use of sequencing for molecular diagnosis is recommended …”

“…One other common theme is the fact that not only can exome sequencing identify the underlying genetic aetiology for many fetuses with structural anomalies, aiding prenatal genetic diagnosis and thus parental counseling, it also helps us understand the prenatal phenotypes of diseases well recognised postnatally. This is highlighted in the review by Petracchi who advocates the use of whole exome sequencing (WES), as the prenatal appearance of a genetic syndrome may not always be concordant with the postnatal features we recognise, making a targeted approach to diagnosis with gene panels less useful as associations between fetal phenotypes and genetic changes continue to emerge . Gray and colleagues expand on this and show how fetal phenotype‐genotype correlations can be broad and disparate from the paediatric presentations we recognise.…”

“…As with other systems, the multidisciplinary approach and use of sequencing for molecular diagnosis is recommended. 21 Many of the articles published in this special issue demonstrate how careful and detailed ultrasound or other imaging modalities can aid prenatal diagnosis of genetic syndromes, from the identification of tooth germs for the diagnosis of X-linked hypohidrotic ectodermal dysplasia 22 to the detailed and sometimes subtle findings in Beckwith Wiedemann syndrome. 23 They also highlight the value of exome sequencing for genetic diagnosis in conditions with overlapping phenotypes that can be very heterogeneous as for example in Aicardi-Goutieres syndrome.…”