Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement

Marcella Zollino, Christiane Zweier, Ingrid D. Van Balkom, David A. Sweetser, Joseph Alaimo, Emilia K. Bijlsma, Jannine Cody, Sarah H. Elsea, Irina Giurgea, Marina Macchiaiolo, Robert Smigiel, Ronald L. Thibert, Ingrid Benoist, Jill Clayton-Smith, Channa F. De Winter, Stijn Deckers, Anusha Gandhi, Sylvia Huisman, Dagmar Kempink, Frea KruisingaVittoria Lamacchia, Giuseppe Marangi, Leonie Menke, Paul Mulder, Ann Nordgren, Alessandra Renieri, Sue Routledge, Carol J. Saunders, Agnieszka Stembalska, Hans Van Balkom, Sandra Whalen, Raoul C. Hennekam

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations


Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.

Original languageEnglish (US)
Pages (from-to)462-478
Number of pages17
JournalClinical Genetics
Issue number4
StatePublished - Apr 2019


  • Pitt-Hopkins syndrome
  • TCF4
  • autonomic dysfunction
  • diagnostic criteria
  • guidelines
  • molecular diagnostic pathway
  • syndromic behavior

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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