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GENATLAS PHENOTYPE
last update : 31-01-2015
Symbol PTHS
Location 18q21.2
Name Pitt-Hopkins syndrome
Other name(s)
  • encephalopathy, severe epileptic, with autonomic dysfunction
    • mental retardation, syndromal, with intermittent hyperventilation
    Corresponding gene TCF4
    Other symbol(s) PHS
    Main clinical features
  • mental retardation, wide mouth and intermittent overbreathing
  • severe psychomotor delay, epilepsy, and daily bouts of diurnal hyperventilation starting in infancy, mild postnatal growth retardation, postnatal microcephaly
  • happy disposition or unmotivated laughter episodes, muscular hypotonia, severe constipation or Hirschprung disease, single palmar creases, and supernumerary digital flexion creases
  • at MRI, anomalies such as hypoplastic corpus callosum and bulging caudate nuclei
    • Genetic determination autosomal dominant
    Related entries PTHS2, PTHS3
    Function/system disorder mental retardation
    respiratory
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types   haploinsufficiency  
      deletion haploinsufficiency 1.2 Mb microdeletion in one patient
    Remark(s) . PTHS-causing mutations create hypomorphic, non-functional and dominant-negative TCF4 alleles (PMID: 22460224))
    Genotype/Phenotype correlations
  • impacts of PTHS-causing mutations vary in severity from partial loss-of-function to dominant-negative effects and functionally unequal mutations are found among deletions and truncating mutations as well as missense mutations in TCF4 (PMID: 22460224))