The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria

Giuseppe Marangi, Pietro Chiurazzi, Domenica Immacolata Battaglia, Marcella Zollino, Stefania Ricciardi, Daniela Orteschi, Serena Lattante, Marina Murdolo, Chiara Biscione, Rosetta Lecce, Donatella Lettori, Gessica Vasco, B Dallapiccola, C Romano, D Greco, R Pettinato, G Sorge, C Pantaleoni, E Alfei, I ToldoC Magnani, P Bonanni, F Martinez, G Serra, A Baroncini, C Daolio

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

43 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1536-1545
Numero di pagine10
RivistaAMERICAN JOURNAL OF MEDICAL GENETICS. PART A
Volume155A
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 18
  • Facies
  • Female
  • Gene Deletion
  • Gene Order
  • Humans
  • Hyperventilation
  • Intellectual Disability
  • Male
  • Mutation
  • Phenotype
  • Transcription Factors
  • Translocation, Genetic

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