Cardiac Involvement and TBCK‐Related Neurodevelopmental Disorder: Is It a New Feature of This Condition?

ABSTRACT TBCK (TBC1 Domain‐Containing Kinase) encodes a protein playing a role in actin organization and cell growth/proliferation via the mTOR signaling pathway. Deleterious biallelic TBCK variants cause Hypotonia, infantile, with psychomotor retardation and characteristic facies 3. We report on three affected sibs, also displaying cardiac malformations. The parents, a consanguineous couple of first cousins, were referred to schedule invasive diagnosis for their sixth pregnancy. They were known to carry the pathogenic c.1532G>A TBCK variant. The variant was originally identified in homozygosity in the first and second children of the couple, both affected. One also presented a right‐sided aortic arch. The other had Tetralogy of Fallot. Present pregnancy ultrasound revealed cystic hygroma and hypoplastic nasal bone, not previously reported in this condition. Chromosomal microarray analysis found no imbalance and identified 8.6% runs of homozygosity. Whole exome sequencing confirmed the TBCK variant without additional pathogenic or candidate variants. Fetal echocardiography revealed left ventricle and aortic arch hypoplasia. The couple opted for pregnancy termination. Fetopsy confirmed sonographic findings and revealed a hypoplastic aorta arising from right ventricle and corpus callosum agenesis. Interestingly, the cardiac phenotype segregates with variants and cardiac involvement might be considered a new feature of this variant causing Hypotonia, infantile, with psychomotor retardation and characteristic facies 3.