Pitt-Hopkins syndrome (PTHS)

What is Pitt-Hopkins syndrome (PTHS)?

PTHS is a rare genetic condition that causes breathing problems, stomach issues and seizures. Children with PTHS also have low muscle tone (hypotonia) and poor coordination. It takes them longer to reach certain developmental milestones like rolling over and sitting. They’re often unsteady when they walk and may need walking-assist devices such as walkers or wheelchairs.

Many children with PTHS never talk in complete sentences. About 1% to 3% of people with PTHS have intellectual disabilities.

PTHS is an autism spectrum disorder (ASD).

What are the different types of Pitt-Hopkins syndrome (PTHS)?

Certain genetic changes cause symptoms similar to PTHS. Children with these types often have more severe intellectual problems, but they can move around better.

• Pitt-Hopkins syndrome - Children with PTHS have developmental and motor delays. They may have seizures, an unusual way of breathing and distinctive facial features. Mutations (changes) in a gene called TCF4 cause PTHS.

• Pitt-Hopkins-like syndrome-1 - Children with Type 1 may only be a little late in developing motor skills like rolling over and sitting up. They don’t usually have the same distinct facial features associated with PTHS. Mutations in a gene called CNTNAP2 cause Pitt-Hopkins-like syndrome-1.

• Pitt-Hopkins-like syndrome-2 - Similar to Type 1, these children may have no motor delays or mild delays. Other symptoms are similar to PTHS. Mutations in a gene called NRXN1 cause Pitt-Hopkins-like syndrome-2.

What are the signs and symptoms of Pitt-Hopkins syndrome (PTHS)?

PTHS symptoms often appear during an infant’s first year. Floppiness or poor muscle control is a key sign, as well as poor coordination (ataxia). A child with PTHS may be late to roll over, sit up or grab for things. If they’re able to walk, they may be wobbly and need a walker or leg braces for support.

Children with PTHS often alternate between taking rapid, shallow breaths (hyperventilation) and then holding their breaths until they turn blue. This behavior most commonly occurs in children ages 5 to 10.

Other signs of PTHS include:

• Behavioral problems, such as hyperactivity or anxiety

• Constipation, reflux and other digestive issues

• Happy dispositions with lots of laughter

• High pain threshold

• Nonverbal (use of simple words or hand gestures to communicate)

• Repetitive movements like flapping hands or rocking

• Seizures (epilepsy)

• Vision problems, such as nearsightedness, crossed eyes or astigmatism (curved lens)

• Undescended testicles (UDT) in boys

A child with PTHS may also have unique physical features, such as:

• Big gaps between teeth

• Broad, flared nose

• Creased palms (hands)

• Flat feet

• Full, puffy cheeks

• Prominent chin

• Small head, hands and feet

• Sunken eyes that have a slight upward slant

• Thick, cup-shaped ears

• Wide mouths with a protruding, double-curved upper lip (called a cupid’s bow)

How is Pitt-Hopkins syndrome (PTHS)] diagnosed?

The genetic change that causes PTHS was just identified in 2007. Many doctors either haven’t heard of the syndrome or have little, if any, experience making a diagnosis. This isn’t the case at Children’s Health. We have one of the few programs in the world specializing in PTHS. Our neurodevelopmental neurologists see dozens of children with this syndrome every year.

Other conditions, such as Phelan-McDermid syndrome and Angelman syndrome, cause symptoms similar to PTHS. We have experience distinguishing between these disorders to provide families with an accurate diagnosis.

Diagnostic tests may include:

• Genetic testing to check for chromosomal changes. We prefer to use cheek swabs for these tests, but we sometimes need blood samples.

• Diagnostic evaluations for autism to observe your child performing tasks

• Electroencephalogram (EEG)  to diagnose seizures and measure electrical activity in the brain

• Magnetic resonance imaging (MRI) to assess brain development

• Neurological tests to evaluate muscles, nerves and senses

What causes Pitt-Hopkins syndrome (PTHS)?

A mutation (change) in the TCF4 gene causes PTHS. This gene is critical to brain and nervous system development. Some children are missing the part of the chromosome (a tiny structure inside the body that carries DNA) that contains the TCF4 gene.

Experts don’t know why these chromosomal changes happen or why some children get PTHS.

How is Pitt-Hopkins syndrome (PTHS) treated?

Children with PTHS need long-term, coordinated care from a team of specialists. Children’s Health brings together all the experts your family needs in one convenient location. Our doctors work together to address all your child’s unique needs.

Treatments vary depending on symptoms and may include:

• Behavioral therapy to manage problems like hyperactivity and to help children function better in the classroom and at home

• Medications to treat seizures, anxiety, stomach problems or other medical problems

• Nutrition counseling to better manage constipation and stomach issues, as well as feeding problems

• Occupational therapy to improve fine motor function and self-care skills like feeding and dressing oneself

• Physical therapy to improve core strength, muscle function and walking

• Speech therapy for feeding issues and to improve communication through simple words, sign language or picture boards