What is Pitt-Hopkins syndrome?
Pitt-Hopkins syndrome is an extremely rare condition that is characterized by intellectual disability, developmental delay, breathing problems, recurrent seizures, and distinctive facial features. There are only approximately 500 affected individuals worldwide.
What causes Pitt-Hopkins syndrome?
Pitt-Hopkins syndrome is caused by mutations in the TCF4 gene, which is a transcription factor that provides instructions for making a protein that helps control the activity of many other genes. Thus, mutations in TCF4 disrupt the protein’s ability to control the activity of these genes, causing the symptoms of Pitt-Hopkins syndrome.
Mutations in this gene are inherited in an autosomal dominant pattern, but most are not inherited and rather, occur spontaneously.
What are the symptoms of Pitt-Hopkins syndrome?
Children with Pitt-Hopkins syndrome are delayed in learning how to walk and developing fine motor skills. They typically do not develop speech and exhibit features of autistic spectrum disorders, including behavioral problems.
The breathing problems in Pitt-Hopkins syndrome can be triggered by emotions (excitement, anxiety, fatigue) and are associated by episodes of hyperventilation followed by periods of apnea, which in turn can lead to a bluish appearance of the skin or lips and loss of consciousness, in severe cases. In addition, the breathing problems may also cause older patients to develop widened and rounded tips of the fingers and toes. Along with these breathing problems, epilepsy also begins during childhood.
The distinctive facial features in individuals with Pitt-Hopkins syndrome include the following:
- Thin eyebrows
- Sunken eyes
- Prominent nose with a high nasal bridge
- Exceptionally pronounced Cupid’s bow
- Wide mouth with full lips and widely spaced teeth
- Thick and cup-shaped ears
In addition to all of these characteristic symptoms of the disorder, the following are also common symptoms:
- Gastrointestinal problems, such as constipation
- Unusually small head
- Eyes that do not look in the same direction
- Short stature
- Minor brain abnormalities
How is Pitt-Hopkins syndrome diagnosed?
Pitt-Hopkins syndrome is diagnosed based on a thorough clinical examination and a detailed patient and family history review. After an observation of the clinical features of the disease, an EEG and cerebral MRI and molecular genetic testing can be used to confirm a diagnosis and distinguish it from Angelman syndrome or Rett syndrome.
What are the available treatments for Pitt-Hopkins syndrome?
The course of Pitt-Hopkins syndrome is non-progressive, but there is no cure. Thus, treatment is symptomatic and supportive, to diminish the impact of symptoms and improve the overall quality of life for patients.