There is not a certain diagnostic criteria, but there are a few symptoms that support a diagnosis of PTHS. Some examples are: facial dysmophism, early onset global developmental delay, moderate to severe intellectual disability, breathing abnormalities, and a lack of other major congenital abnormalities. Half of the individuals with PTHS are reported to have seizures, starting from childhood to the late teens. Around 50% of those affected show abnormalities on brain imaging. These include a hypoplastic corpus callosum with a missing rostrum and posterior part of the splenium, with bulbous caudate nuclei bulging towards the frontal horns. Electroencephalograms show an excess of slow components. According to the clinical diagnosis. PTHS is in the same group as Pervasive Developmental Disorders. When a patient is suspected of having PTHS, genetic tests looking at the TCF4 gene are typically done. Differential diagnosis PTHS is symptomatically similar to Angelman syndrome, Rett syndrome and Mowat–Wilson syndrome. Angelman syndrome most closely resembles PTHS. Both have absent speech and a "happy" disposition. Of the differentials, Rett syndrome is the least close to PTHS. This syndrome is seen as a progressive encephalopathy. Both Angelman syndrome and Rett syndrome lack the distinctive facial features of PTHS. Mowat–Wilson syndrome is seen in early infancy and is characterized by distinctive facial abnormalities.
Pitt–Hopkins syndrome
Hypotrichosis–lymphedema–telangiectasia syndrome
Kasabach–Merritt syndrome
SUNCT syndrome
Rapp–Hodgkin syndrome
Schwartz–Matsuo syndrome
Franceschetti–Klein syndrome
Swyer–James syndrome