Diagnosis of Kabuki syndrome with unreported KMT2D pathogenic variant: contribution of prenatal facial dysmorphology analysis and whole exome sequencing – about a clinical report and review of the literature

Abstract

Kabuki syndrome (KS) defines a rare heterogenous clinical genetic disorder confirmed by identification of heterozygous mutations in KMT2D or KDM6A genes. Postnatal hallmarks include developmental delay, distinctive facial dysmorphism and multiple congenital anomalies. Current report presents prenatal findings of a fetus diagnosed postnatally with a so far unreported KMT2D pathogenic variant. The prenatal phenotype of KS is highly variable and non-specific. Congenital cardiac left-sided lesion associated with poor fetal growth, abnormal aspect of the external ear and polyhydramnios was observed in our case. An accurate 3D-analysis of the fetal face at the 25th, 30th and 34th week of gestation was not helpful for the diagnosis, except for the external ear evaluation. KS can be diagnosed during the pregnancy as whole exome sequencing (WES) has shown a particular benefit at improving the diagnosis yield with non-isolated congenital cardiac defects after absence of submicroscopic pathogenic copy number variations (CNVs) on molecular karyotype. Update recommendation on the use of WES in pregnancies with multiple congenital anomalies and heart defect should definitively increase prenatal diagnosis of KS in order to provide precise genetic counselling, giving parents the option to choose whether to continue or not the pregnancy or to prepare the childcare at birth.