Clinical and genetic characteristic of patients with Pitt–Hopkins syndrome

Abstract

Background. PittHopkins syndrome (PHS) is the rare inherited disease, caused by a microdeletion on chromosome 18q21 or heterozygous mutation TCF4 gene and characterized by severe mental retardation, abnormal breathing patterns: hyperventilation, apnea, and unusual facial features.
 Material and method. We examined 9 children, included 4 boys and 5 girls at the age of 1 year 8 months to 12 years with PHS. All children have clinical symptoms characteristic of this syndrome. The diagnosis was confirmed by Array CGH (deletion of genomic material in chromosomal region 18q21) and new generation sequencing.
 Results. Microdeletions chromosome 18 (18q21) were identified in 5 patients. The size of the microdeletions varied from 307 Kb to 11.62 Mb. A point mutation was detected in 4 children: two patients had a mutation in the splicing site, 1 missense and 1 nonsense-mutation. The clinical picture was analyzed in all children: psychomotor retardation, severe intellectual disability, poor speech, autistic behavior, hypotonia, and specific phenotype.
 Conclusion. Comparative analysis of the clinical picture in patients with PHS, caused by a microdeletion on chromosome 18q21 and point mutation in the TCF4 gene showed that no significant clinical differences were found. The main clinical criteria for suspecting PHS are gross developmental delay, severe delayed psychomotor development, behavioral disorders, and episodes of hyperventilation with the subsequent apnea.