Pitt Hopkins syndrome – TCF4 gene deletion causing severe psychomotor delay

Abstract

Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder due to haploinsufficiency of TCF4 and is clinically characterized by developmental delay, intellectual disability (ID), autism spectrum disorders, typical facial gestalt, seizures, high myopia and hyperventilation-apneic spells. Approximately in three-fourth cases of PTHS, a de novo pathogenic variant in TCF4 is identified. In other instances, deletion of the chromosome region 18q21.2 in which encompasses TCF4 is responsible and only chromosomal microarray (CMA) can reveal the microdeletion. This report describes the case of a 10 year-old girl with PTHS phenotype caused by a chromosome 18q21.2q22.1 deletion that included the TCF4 gene. The patient had severe developmental and cognitive delay, autistic spectrum disorder, motor difficulties, and behavioral issues, all of which are typical with PTHS. Understanding the phenotypic variation is critical for accurate diagnosis in this syndrome, since deletions in TCF4 may be missed if exome sequencing is sought instead of chromosomal microarray analysis (CMA).