Pitt Hopkins syndrome (PHS) is a severe congenital encephalopathy that occurs in approximately 1 in 40,000 individuals. PHS is characterized by severe mental retardation and characteristic facial features, including enopthalmia, large beaked nose, wide mouth, fleshy lips and widely spaced teeth. Other commonly observed features invlude hyperventilation episodes, epilepsy, acquired microcephaly, short stature, strabismus, myopia and brain abnormalities such as hypoplasia of the corpus callosum. The PHS phenotype overlaps with Angelman, Mowat-Wilson and Rett syndrome.
PHS is associated with mutations in the gene, TCF4, located at 18q21.1. De Pontual et al  detected TCF4 mutations in 13 of 36 patients with severe psychomotor delay and facial features consistent with PHS, some of whom had previously been investigated for Angelman, Mowat-Wilson and Rett syndrome. Giurgea et al  detected deletions of the TCF4 gene in 4 of 30 patients initially evaluated for Angelman, Mowat-Wilson, or Rett syndrome whose phenotype overlapped PHS.
Deletions and/or duplications in the TCF4 gene as causative of Pitt Hopkins syndrome have been reported.
Contact the Pitt Hopkins Syndrome International Network (http://sites.google.com/site/pitthopkinssyndrome/) for more information and support.