Issue 4/2025, Брой 4/2025, Articles

Two clinical cases of Pitt-Hopkins syndrome

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T. Aleksandrova1, T. Delchev1,2, Ts. Veleva1,2, D. Avdjieva-Tzavella1,2

1Department of Clinical genetics, SBAL Children’s Hospital „Prof. Dr. Ivan Mitev“ 2Medical University – Sofia

Abstract

Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder characterized by significant developmental delay with moderate-to-severe intellectual disability, severely limited-to-absent speech, distinctive facial dysmorphism, behavioral abnormalities and autonomic dysregulation. The condition is predominantly associated with de novo variants and deletions affecting the TCF4 gene. Clinical diagnosis is often challenging due to significant phenotypic overlap with Angelman syndrome and Angelman-like syndromes. A conclusive diagnosis is established through molecular genetic testing. Тo date, no curative therapy has been established. Here, we present two genetically confirmed cases from our practice, both demonstrating the typical phenotype and clinical features of Pitt-Hopkins syndrome.

Key words: Pitt-Hopkins syndrome, PTHS, TCF4, Angelman-like syndrome

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Address for correspondence:

Т. Аleksansdrova

Department of Clinical genetics, SBAL Children‘s Hospital “Prof. Dr. Ivan Mitev” – Sofia

11, “Acad. Ivan Evstatiev Geshov”, Blvd.

1606, Sofia

е-mail: teodora.aleksandrova14@gmail.com