Disease Directory Pitt-Hopkins Syndrome
Neurological

Pitt-Hopkins Syndrome

Also known as: PTHS, TCF4 haploinsufficiency, Pitt-Hopkins-like syndrome

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Infantile, Childhood

Type

Autosomal dominant genetic (de novo in most cases)

Gene

TCF4

About Pitt-Hopkins Syndrome

Pitt-Hopkins syndrome is a neurodevelopmental disorder caused by haploinsufficiency of TCF4 (transcription factor 4), encoding a basic helix-loop-helix transcription factor involved in brain development. Clinical features include intellectual disability, absence or severe impairment of speech, distinctive facial features (wide mouth, prominent nasal bridge, widely spaced teeth), breathing abnormalities (episodic hyperventilation followed by apnea), epilepsy, and behavioral features overlapping with autism spectrum disorder.

Common Clinical Features

Severe intellectual disability Absent or limited speech Breathing abnormalities (episodic hyperventilation/apnea) Distinctive facial features Seizures Autism spectrum features Constipation

Clinical Trial Eligibility Tips

What to know before applying to Pitt-Hopkins Syndrome trials.

TCF4 pathogenic variant (deletion, truncating mutation, or missense) confirmed by array CGH or sequencing is required

Breathing pattern documentation (episodic hyperventilation/apnea) is a diagnostic feature — overnight oximetry may be required

Communication and adaptive behavior assessments (Vineland, DEAP, non-verbal cognitive measures) are required baseline tools

Pitt-Hopkins-like syndromes (CNTNAP2, NRXN1) are genetically distinct — specific TCF4 confirmation avoids misclassification in trials

Patient Resources

Patient Organization

Pitt Hopkins Research Foundation

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Natural History Registry

Pitt Hopkins Patient Registry

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Orphanet

European reference resource for rare diseases (ORPHA:2896)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Pitt-Hopkins Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Pitt-Hopkins Syndrome. Updated daily.

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