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

Zollino, M., Zweier, C., Van Balkom, I. D., Sweetser, D. A., Alaimo, J., Bijlsma, E. K., Cody, J., Elsea, S. H., Giurgea, I., Macchiaiolo, M., Smigiel, R., Thibert, R. L., Benoist, I., Clayton-Smith, J., De Winter, C. F., Deckers, S., Gandhi, A., Huisman, S., Kempink, D., Kruisinga, F., Lamacchia, V., Marangi, G., Menke, L., Mulder, P., Nordgren, A., Renieri, A., Routledge, S., Saunders, C. J., Stembalska, A., Van Balkom, H., Whalen, S. & Hennekam, R. C., Apr-2019, In : Clinical Genetics. 95, 4, p. 462-478 17 p.

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

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  • 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 Kruisinga
  • Vittoria 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

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
Pages (from-to)462-478
Number of pages17
JournalClinical Genetics
Issue number4
Publication statusPublished - Apr-2019


  • autonomic dysfunction, diagnostic criteria, guidelines, molecular diagnostic pathway, Pitt-Hopkins syndrome, syndromic behavior, TCF4, CENTRAL SLEEP-APNEA, HELIX TRANSCRIPTION FACTOR, MENTAL-RETARDATION, INTELLECTUAL DISABILITY, TCF4 GENE, PEDIATRIC GASTROENTEROLOGY, EUROPEAN-SOCIETY, CLINICAL SCORE, FACTOR E2-2, DELETION

ID: 92807678