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.

dx.doi.org/10.1136/jmg.2008.060129, hdl.handle.net/1765/28862
Journal of Medical Genetics
Erasmus MC: University Medical Center Rotterdam

Zweier, C, Sticht, H, Bijlsma, E.K, Clayton-Smith, J, Boonen, S.E, Fryer, A, … Rauch, A. (2008). Further delineation of Pitt-Hopkins syndrome: Phenotypic and genotypic description of 16 novel patients. Journal of Medical Genetics, 45(11), 738–744. doi:10.1136/jmg.2008.060129