The majority of our children have both a genetic and a clinical diagnosis of PTHS. For a genetic or molecular diagnosis, a sample of DNA is isolated from blood, and chromosomal deletion at 18q21.2, or a mutation in the Tcf4 gene on chromosome 18 confirms the diagnosis of PTHS. A clinical diagnosis requires the judgment of a clinician and is based on identifying the phenotype or physical characteristics associated with PTHS. In most cases, individuals with the genetic findings for PTHS exhibit some or all of the phenotypic characteristics of PTHS. In some cases, individuals have been diagnosed clinically, before the advent of genetic testing for PTHS. In rare cases, geneticist are unable to locate the genetic lesion associated with PTHS, but the characteristics of the individual in question are so compelling that the diagnosis is made.

Rarely, individuals have been identified with mutation in Tcf4 (genetic diagnosis) and mild intellectual disability. If they lack the facial appearance for PTHS as well as other “syndromic” aspects of PTHS, the clinical diagnosis may be “non-syndromic intellectual disability.”