Severe Dilated Cardiomyopathy in a Child with Pitt-Hopkins Syndrome

Abstract A 6-months old girl presented with dilated cardiomyopathy (dCMP) with severe left ventricle dysfunction. Surgical pulmonary artery banding was performed, with successful weaning of ventilator despite persistent cardiac dysfunction. Despite the lack of extra-cardiac symptoms at initial presentation, the patient progressively developed marked global developmental delay, stereotypical hand and head movements, and growth retardation, initially thought to be related to the persistent cardiac condition. SNP-array and panel testing for cardiomyopathy and lysosomal storage diseases were noncontributing. Trio exome sequencing revealed a de novo likely pathogenic variant in TCF4 establishing the molecular diagnosis of Pitt-Hopkins Syndrome (PTHS) and explaining the non-cardiac features. As far as we know, this is the first patient described with the association of dCMP and PTHS. We did not detect other known genetic etiologies for dCMP on targeted panel analysis nor in the exome. Systematic unbiased assessment of infantile dCMP patients in the future will therefore be crucial to confirm a possible relationship between TCF4 variants and dCMP. In conclusion, multidisciplinary approach in patients with dCMP contributes to novel insights. With a genetic diagnosis, precision medicine approaches including major therapeutic decisions such as heart transplantation are clearly considered differently. This makes an important difference for the patient, parents, and medical team.