Prenatal diagnosis of recurrent hypoplastic left heart syndrome associated with MYH6 variants: a case report

• Published in: BMC cardiovascular disorders Vol. 23; no. 1; pp. 116 - 6
• Main Authors: Najib, B, Quibel, T, Tessier, A, Mortreux, J, Bouvagnet, P, Cohen, C, Vialard, F, Dard, R
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-03-2023; BioMed Central; BMC
• Subjects: Amniotic fluid; Analysis; Aortic stenosis; Cardiac Myosins - genetics; Cardiomyopathy; Cardiovascular disease; Care and treatment; Case Report; Case reports; Congenital diseases; Congenital heart disease; Coronary vessels; Development Biology; Diagnosis; Etiology; Family medical history; Female; Fetuses; Genetic aspects; Genomes; Genomics; Health aspects; Heart; Heart Defects, Congenital - genetics; Heart diseases; Heredity; Heterozygosity; Humans; Hypoplastic left heart syndrome; Hypoplastic Left Heart Syndrome - diagnostic imaging; Hypoplastic Left Heart Syndrome - genetics; Hypotheses; Infant, Newborn; Life Sciences; Methods; Mutation; MYH6; MYH7; Myosin Heavy Chains - genetics; Neonates; Parents & parenting; Pregnancy; Prenatal Diagnosis; Reproductive technology; Transvaginal ultrasonography; Ultrasonic imaging; France; Case report; Congenital heart disease; Hypoplastic left heart syndrome; MYH6; MYH7; Hypoplastic left heart syndrome MYH6 MYH7 Congenital heart disease Case report
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-023-03169-z

Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD).
Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants.
The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology.