2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-<em>SF3B2</em>-Related Cardiac Defects and Hirschsprung Disease without craniofacial microsomia

Pdf Summary

This case report discusses a patient with haploinsufficiency of SF3B2, a gene associated with craniofacial spliceosomopathy syndrome. The patient is an 8-year-old female with complex congenital heart disease (CHD) and Hirschsprung's disease, but lacks the craniofacial microsomia typically seen in SF3B2-related syndrome.<br /><br />The patient has ventricular septal defect with right ventricular outflow tract obstruction, secundum atrial septal defect, pulmonary stenosis, Hirschsprung's disease, and recurrent recto-vaginal fistula. Duo exome sequencing revealed a maternally inherited likely pathogenic variant in SF3B2.<br /><br />Although craniofacial microsomia is a defining feature of SF3B2-related syndrome, this patient did not exhibit this feature or other dysmorphic characteristics. However, prior research has indicated that SF3B2 knockdown interferes with neural crest (NC) development, which is relevant to Hirschsprung's disease as NC-derived cartilages are hypoplastic or missing in Xenopus morphants with SF3B2 knockdown.<br /><br />The authors suggest that the association between SF3B2 and Hirschsprung's disease is likely, despite being previously unreported. They anticipate that further identification of SF3B2 variants in patients will expand the phenotypic spectrum of the disorder. Therefore, they propose that this condition be described as "SF3B2-related disease."<br /><br />The authors express gratitude to the participating family and their colleagues in the Children's Mercy Clinical Genetics Laboratories. They provide a reference to Timberlake et al., 2021, which likely provides more information on the subject.<br /><br />Overall, this case report highlights a patient with SF3B2-related disease characterized by CHD and Hirschsprung's disease, further expanding the understanding of the phenotypic manifestations of SF3B2 variants.

Asset Subtitle

Co-Author - Florencia Del Viso, PhD; Co-Author - Dihong Zhou, MD; Co-Author - Susan Starling, Genetics Counselor; Co-Author - Emily A. Fleming, Genetics Counselor; Presenting Author - Carol J. Carol, PhD;

Meta Tag

Phenotype

Identification of Disease Genes

Genetic Testing

Exome sequencing

Delineation of Diseases

Congenital Anomaly

Cardiovascular System

Bioinformatics

Co-Author Emily A. Fleming, Genetics Counselor

Co-Author Susan Starling, Genetics Counselor

Co-Author Dihong Zhou, MD

Co-Author Florencia Del Viso, PhD

Presenting Author Carol J. Carol, PhD

Keywords

SF3B2

craniofacial spliceosomopathy syndrome

haploinsufficiency

complex congenital heart disease

Hirschsprung's disease

ventricular septal defect

pulmonary stenosis

duo exome sequencing

phenotypic spectrum

SF3B2-related disease