What It Is

Pitt Hopkins Syndrome (PTHS) is a rare genetic disorder resulting from a mutation of the TCF4 gene or a deletion in the region of the 18th chromosome where the TCF4 gene is located.  TCF4 is a transcription factor, so mutations or deletions in this region disrupt the body's ability to carry out normal nervous system development and function resulting in developmental delay and intellectual disability.  

PTHS is inherited through an autosomal dominant pattern, which means one copy of the altered gene is all that's needed to cause PTHS.  However, most cases result from new mutations with no history of disorder in the family.

There are approximately 250 known individuals with PTHS.  However, with advancements in molecular genetic testing and microarray analysis, that number is expected to rise.


Developmental Delay and Intellectual Disability- Individuals with PTHS have moderate to severe intellectual disability.  Motor skills including walking are generally quite delayed.  Children with PTHS often have a wide-based, unsteady gait.  Expressive language is limited or absent, though for some people with PTHS receptive language skills are relatively intact.  Multimodal strategies including gesture, symbol exchange, and voice-output devices enable communication for some affected persons.

Breathing Issues- Hyperventilation (rapid breathing) followed by periods of apnea (slowed breathing or breath holding) can be triggered by emotions or fatigue.  These breathing anomalies disappear in sleep.  Individuals may appear blue in the lips or skin, lose consciousness, and develop clubbed (widened and rounded) fingers and toes due to chronic, decreased levels of oxygen.

Epilepsy-  Recurring seizures affect about half the people diagnosed with PTHS.

Eyes and Vision- Vision problems are common in people with PTHS and may include crossed eyes (strabismus), and severe near-sightedness (myopia). 

Facial features include a prominent nose with flattened nasal bridge, pronounced double curve of upper lip (Cupid's bow), wide mouth, full lips, and widely spaced teeth.  Thick and cup shaped ears are noted for many people with PTHS.  In profile, the lower part of the face may extend slightly beyond the upper part of the face.

Constipation is a prominent feature of PTHS.   Other gastrointestinal issues including reflux and food allergies are not uncommon.

Affected individuals often have a happy and excitable demeanor with frequent smiling, laughing, and hand flapping.  PTHS is in the differential for Angelman's Syndrome as both share features of cognitive disability, motor impairment and happy demeanor.  Persons with PTHS may also experience behavioral issues including hyperactivity and anxiety.  Some meet criteria for an autism spectrum disorder.

Treatments & Therapies

Currently there is no known cure for Pitt Hopkins Syndrome and treatment is symptomatic.

Affected persons often benefit from glasses and assistive communication devices.  Symptoms like seizures, hyper breathing and constipation are managed with medication.  Physical therapy, hippotherapy, standers and braces are just some modalities used to help individuals build strength in order to lessen physical limitations.  Speech, sensory integration and behavioral therapies can also help increase quality of life for an affected individual.

  • The description of this disease is provided courtesy of the NIH, and other sources.
  • The information provided on this web site should NOT be used as a substitute for seeking professional medical diagnosis, treatment or care. You should not rely on any information in these pages to replace consultations with qualified health professionals.