Clinical

Syndromes: Pitt-Hopkins syndrome

A rare genetic disease that affects both sexes where delayed development of communication skills and impairments in social interactions are common
DNA helix

A rare genetic disease that affects both sexes where delayed development of communication skills and impairments in social interactions are common

Pitt-Hopkins syndrome (PTHS) is a rare genetic disease first described by Australian physicians David Pitt and Ian Hopkins in 1978.

To date, only 500 confirmed clinical cases of PTHS have been described worldwide ( Sparber et al 2020 ), although the true global prevalence is unknown.

Estimates based on unpublished case data in the UK and the Netherlands range from one case per 225,000 people to one per 300,000. Severe intellectual disabilities are indicated in 98% to 100% of confirmed cases (

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A rare genetic disease that affects both sexes where delayed development of communication skills and impairments in social interactions are common

Pitt-Hopkins syndrome. DNA helix
Picture: iStock

Pitt-Hopkins syndrome (PTHS) is a rare genetic disease first described by Australian physicians David Pitt and Ian Hopkins in 1978.

To date, only 500 confirmed clinical cases of PTHS have been described worldwide (Sparber et al 2020), although the true global prevalence is unknown.

Estimates based on unpublished case data in the UK and the Netherlands range from one case per 225,000 people to one per 300,000. Severe intellectual disabilities are indicated in 98% to 100% of confirmed cases (Zollino et al 2019). 

Be cautious when diagnosing Pitt-Hopkins syndrome

PTHS affects both sexes and is caused by an abnormal expression of the transcription factor 4 (TCF4) gene, leading to deletions or mutations on the 18th chromosome. Global developmental delay and intellectual disabilities are usually apparent in the first year of life.

Diagnosis is made using genetic testing in combination with clinical diagnostic criteria based on physical, developmental and psychosocial phenotypical indicators. Caution is advised when diagnosing PTHS due to phenotypic overlap with neurological disorders such as Angelman syndromeRett syndrome and Cornelia de Lange syndrome (Bonello et al 2017Watkins et al 2019).

Dysmorphic physical and skeletal features

Peter is 19 years old and lives at home with his parents. He was born full-term and there were no complications during the pregnancy or delivery. Diagnosis of PTHS was made at 24 months after genetic testing indicated by delayed global development and observation of facial features that included a flattened mid-face, hypotelorism and a Cupid’s bow lip.  From an early age, Peter experienced episodic apnoea and cyanosis. Over the past two months he has begun having tonic-clonic seizures shortly after some apnoeic episodes.  Following a neurological assessment, Peter was diagnosed with epilepsy. His parents now understand his apnoea is caused by anxiety or excitement.  Using a social story, Peter was assisted to attend for an electroencephalogram and he is offered relaxation therapies. The epilepsy nurse specialist has developed an epilepsy management plan for Peter, and he also receives an annual health assessment and health action plan.
Picture: Wikimedia Commons

PTHS can lead to a number of dysmorphic physical and skeletal features including:

  • Narrow forehead.
  • Wide nasal bridge.
  • Cupid’s bow upper lip.
  • Microcephaly.
  • Scoliosis.

Individuals with PTHS will often present with chronic and severe constipation, breathing anomalies such as intermittent hyperventilation or waking apnoea, hypotonia and delayed gross motor development (Zollino et al 2019).

Delayed development of communication skills and impairments in social interactions are common. Repetitive play and stereotypical motor behaviours occur more often than in other individuals with severe intellectual disabilities.

The behavioural phenotype may also include agitation, anxiety, self-injurious behaviour and autism spectrum disorder (van Balkom et al 2012). Epileptic seizures occur in 37% to 50% of cases, with onset between the first year of life and early adulthood (Zollino et al 2019).

Diagnosis of Pitt-Hopkins syndrome at 24 months

Peter is 19 years old and lives at home with his parents. He was born full-term and there were no complications during the pregnancy or delivery. Diagnosis of PTHS was made at 24 months after genetic testing indicated by delayed global development and observation of facial features that included a flattened mid-face, hypotelorism and a Cupid’s bow lip.

From an early age, Peter experienced episodic apnoea and cyanosis. Over the past two months he has begun having tonic-clonic seizures shortly after some apnoeic episodes.

Following a neurological assessment, Peter was diagnosed with epilepsy. His parents now understand his apnoea is caused by anxiety or excitement.

Using a social story, Peter was assisted to attend for an electroencephalogram and he is offered relaxation therapies. The epilepsy nurse specialist has developed an epilepsy management plan for Peter, and he also receives an annual health assessment and health action plan.

 

Potential benefits of a speech and language therapy assessment

PTHS was only discovered in the 1970s, so it is not known whether it is a life-limiting condition. But given the complexity of symptoms and comorbid conditions, individuals are likely to require considerable support to maintain physical well-being. A multidisciplinary needs assessment is recommended (Zollino et al 2019). 

Breathing abnormalities result in cyanosis and fainting, but these are not associated with lasting neurological damage. Individuals may benefit from a speech and language therapy assessment due to the increased risk of respiratory tract infections.

Supportive and adaptive communication systems will assist individuals with PTHS to communicate pain and distress effectively (Goodspeed et al 2018). Pain resulting from gastrointestinal disturbances, such as constipation, is linked with anxiety and self-injurious behaviour. Constipation may respond to positive behavioural support, toilet sitting after meals and accurate evaluation using constipation diaries (Zollino et al 2019).

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References


Paul Francis McAleer, lecturer in the School of Nursing and Midwifery, Queen's University BelfastPaul McAleer, @paulfmca, is a lecturer in the School of Nursing and Midwifery, Queen's University Belfast

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