Further delineation of Pitt–Hopkins syndrome: phenotypic and genotypic description of 16 novel patients
- C Zweier1,
- H Sticht2,
- E K Bijlsma3,
- J Clayton-Smith4,
- S E Boonen5,
- A Fryer6,
- M T Greally7,
- L Hoffmann8,
- N S den Hollander3,
- M Jongmans9,
- S G Kant3,
- M D King10,
- S A Lynch7,
- S McKee11,
- A T Midro12,
- S-M Park13,
- V Ricotti10,
- E Tarantino14,
- M Wessels15,
- M Peippo16,
- A Rauch1
- 1Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- 2Bioinformatics, Institute of Biochemistry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- 3Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
- 4Academic Department of Medical Genetics and Regional Genetic Services, St Mary’s Hospital, University of Manchester, Manchester, UK
- 5Kennedy Center, National Research Center for Genetics, Visual Impairment and Mental Retardation, Glostrup, Denmark
- 6Department of Clinical Genetics, Royal Liverpool Children’s Hospital, Liverpool, UK
- 7National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Crumlin, Dublin, Ireland
- 8Department of Pediatrics, Naestved Hospital, Naestved, Denmark
- 9Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
- 10Department of Pediatric Neurology, Children’s University Hospital, Temple Street, Dublin, Ireland
- 11Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK
- 12Department of Clinical Genetics, Medical University Bialystok, Bialystok, Poland
- 13Department of Clinical Genetics, Addenbrooke’s Hospital, Cambridge, UK
- 14Section of Clinical Genetics, Department of Pediatrics, S. Chiara Hospital, Pisa, Italy
- 15Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
- 16The Department of Medical Genetics, Väestöliitto, Helsinki, Finland
- Dr A Rauch, Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany; arauch{at}humgenet.uni-erlangen.de
- Received 30 April 2008
- Revised 24 June 2008
- Accepted 27 June 2008
- Final version accepted 21 August 2008
- Published Online First 26 August 2008
Abstract
Background: Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt–Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation.
Methods: TCF4 mutational analysis was performed in 117 patients with PTHS-like features.
Results: In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies.
Conclusion: This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.
Footnotes
-
Competing interests: None.
-
Patient consent: Parental consent obtained.
