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The Pitt‐Hopkins syndrome: Report of 16 new patients and clinical diagnostic criteria
Author(s) -
Marangi Giuseppe,
Ricciardi Stefania,
Orteschi Daniela,
Lattante Serena,
Murdolo Marina,
Dallapiccola Bruno,
Biscione Chiara,
Lecce Rosetta,
Chiurazzi Pietro,
Romano Corrado,
Greco Donatella,
Pettinato Rosa,
Sorge Giovanni,
Pantaleoni Chiara,
Alfei Enrico,
Toldo Irene,
Magnani Cinzia,
Bonanni Paolo,
Martinez Federica,
Serra Gigliola,
Battaglia Domenica,
Lettori Donatella,
Vasco Gessica,
Baroncini Anna,
Daolio Cecilia,
Zollino Marcella
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.34070
Subject(s) - haploinsufficiency , rett syndrome , tcf4 , angelman syndrome , intellectual disability , medicine , differential diagnosis , neurodevelopmental disorder , psychology , pediatrics , phenotype , psychiatry , genetics , pathology , autism , gene , biology , gene expression , promoter
Pitt‐Hopkins syndrome (PTHS) is characterized by severe intellectual disability, typical facial gestalt and additional features, such as breathing anomalies. Following the discovery of the causative haploinsufficiency of transcription factor 4 ( TCF4 ), about 60 patients have been reported. We looked for TCF4 mutations in 63 patients with a suspected PTHS. Haploinsufficiency of TCF4 was identified in 14 patients, as a consequence of large 18q21.2 chromosome deletions involving TCF4 (2 patients), gene mutations (11 patients) and a t(14q;18q) balanced translocation disrupting TCF4 (one patient). By evaluating the clinical features of these patients, along with literature data, we noticed that, in addition to the typical facial gestalt, the PTHS phenotype results from the various combinations of the following characteristics: intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities. Although PTHS is currently considered to be involved in differential diagnosis with Angelman and Rett syndromes, we found that combining the facial characteristics with a detailed analysis of both the physical and the neurological phenotype, made molecular testing for PTHS the first choice. Based on striking clinical criteria, a diagnosis of PTHS was made clinically in two patients who had normal TCF4 . This report deals with the first series of PTHS patients of Italian origin. © 2011 Wiley‐Liss, Inc.