OBSOLETE: Pitt-Hopkins-like syndrome

Pitt-Hopkins-like syndrome (also referred to as PTHSL) was a clinical designation used to describe conditions that share significant phenotypic overlap with Pitt-Hopkins syndrome but are caused by mutations in different genes. This entry (Orphanet code 221150) is now considered obsolete, as the conditions previously grouped under this umbrella term have been reclassified into more specific diagnostic entities. Historically, Pitt-Hopkins-like syndrome encompassed at least two subtypes: Pitt-Hopkins-like syndrome 1 (PTHSL1), caused by mutations in the CNTNAP2 gene, and Pitt-Hopkins-like syndrome 2 (PTHSL2), caused by mutations in the NREX1 gene. These conditions share core features with classic Pitt-Hopkins syndrome, including severe intellectual disability, absent or severely limited speech, and behavioral features that may overlap with autism spectrum disorder. The key clinical features associated with the conditions formerly grouped as Pitt-Hopkins-like syndrome primarily affect the nervous system. Patients typically present with early-onset developmental delay, severe to profound intellectual disability, limited or absent expressive language, seizures, and stereotypic movements. Some patients may also exhibit breathing abnormalities such as episodic hyperventilation, though these features are more characteristic of classic Pitt-Hopkins syndrome (caused by TCF4 mutations). Gastrointestinal problems, including constipation, may also be present. Because this entry is now obsolete, patients and clinicians are encouraged to refer to the specific subtypes or updated disease classifications for the most accurate diagnostic and management information. There is no cure for these conditions; treatment remains supportive and symptomatic, including speech therapy, physical therapy, seizure management with antiepileptic medications, and behavioral interventions.

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