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.,
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