2.1. Pitt-Hopkins syndrome

At least 50 mutations in the TCF4 gene have been found to cause Pitt-Hopkins syndrome, a condition characterized by severe intellectual disability and breathing problems. Some mutations delete a few building blocks of DNA (nucleotides) within the TCF4 gene, while other mutations delete the TCF4 gene as well as a number of genes that surround it. Still other TCF4 gene mutations replace single nucleotides. The type of the mutation does not appear to affect the severity of the condition.

TCF4 gene mutations disrupt the protein's ability to bind to DNA and control the activity of certain genes. These gene mutations typically do not affect the TCF4 protein's ability to bind to other proteins. The TCF4 protein's inability to bind to DNA and control the activity of certain genes, particularly those genes involved in nervous system development and function, contributes to the signs and symptoms of Pitt-Hopkins syndrome. It is also likely that the loss of the normal proteins that are attached to the nonfunctional TCF4 proteins contribute to the features of this condition.

2.2. Distal 18q deletion syndrome

The TCF4 gene is involved in some cases of a condition called distal 18q deletion syndrome, which occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "distal" means that the missing piece occurs near one end of the chromosome. Distal 18q deletion syndrome can lead to a wide variety of signs and symptoms among affected individuals, depending on which genes in this part of chromosome 18 are affected. People with this disorder whose deletions include the TCF4 gene usually have signs and symptoms of Pitt-Hopkins syndrome (described above) in addition to other features of distal 18q deletion syndrome that are likely associated with the loss of nearby genes.

Fuchs endothelial dystrophy