Pitt-Hopkins syndrome and differential diagnosis [48 genes]

Pitt-Hopkins syndrome is characterized by moderate to severe intellectual disability, characteristic facial features, episodic hyperventilation, and/or breath retention while awake. Other common findings are symptoms of autism spectrum disorders, sleep disorders, stereotyped hand movements, seizures, constipation, and severe myopia.

Pitt Hopkins syndrome: 1 / 225,000-300,000 (ORPHA:2896).

The benefits derived from a genetic diagnosis are aimed at closing the diagnosis and family genetic counseling. It also allows close monitoring of the principal health problems typically associated, such as visual problems.

Service is indicated when, in a patient with intellectual disability, there is, at least, moderate suspicion that the patient suffers from this disease due to behavioral or facial features or due to episodes of hyperventilation/breath holding.

In up to 30% of cases, the variants responsible for the condition are CNVs. An exome approach makes it possible to identify this type of variants along with sequence variants. However, less than 1% of patients with Pitt-Hopkins syndrome suffer from balanced translocations. Therefore, this possibility should be considered whenever the clinical diagnosis is certain but the genetic report has been non-informative.