Pitt-Hopkins syndrome

Emergency Management

It may be important to consider the following when managing individuals living with Pitt-Hopkins syndrome at emergency departments/services:

• Individuals with Pitt-Hopkins syndrome may have severe intellectual disability, with limited or absent speech
• They may need 24/7 attendant/carer support in Emergency and Hospital
• They may not be able to communicate with spoken words and may use alternative communication methods such as key word sign, sign language or Alternative and Augmentative Communication tools and devices
• They may have seizures

Clinical Care Guidelines

We are not aware of any clinical care guidelines for Pitt-Hopkins syndrome in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement – developed by a consensus group consisted of 32 participants (which included clinicians, molecular geneticists, clinical and research scientists, and patient group representatives) from 24 institutions from 7 countries; published in 2019

Personal Stories

Pitt-Hopkins syndrome varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with Rare Voices Australia and have it included on the RARE Portal, please visit Rare Voices Australia: Share Your Story.

Symptoms

Common features of Pitt-Hopkins syndrome include, but are not limited to, the following:^1-3,6-8

• developmental delays
• intellectual disability with limited or no speech
• low muscle tone (hypotonia) in infants
• characteristic facial features, such as narrow forehead, thin lateral eyebrows, broad nasal bridge (top portion of the nose wider than usual), flared nasal alae (nostrils), full cheeks, wide mouth/full lips/cupid bow upper lip (shaped like the letter ‘M’), thickened or overfolded helices of the ears; these features may become more prominent with age
• rapid breathing (hyperventilation)
• pauses in breathing or breath-holding (apnea)
• constipation
• issues with vision, including early-onset short-sightedness (myopia)
• seizures
• repetitive hand gestures and mannerisms
• behavioural attributes, such as anxiety, agitation, a ‘smiling’ appearance, inappropriate laughing as well as other features on the autism spectrum

Further information about the clinical description of Pitt-Hopkins syndrome can be found at GeneReviews®: Pitt-Hopkins syndrome (Clinical Characteristics section).

Please speak to your medical team to learn more about the features and health implications associated with Pitt-Hopkins syndrome.

Cause/Inheritance

Pitt-Hopkins syndrome is a genetic condition caused by genetic changes in the TCF4 gene on Chromosome 18.^4,5 Reported genetic changes include single base changes (sequence variants), small and large deletions, insertions, duplications as well as translocations that span the TCF4 locus.^4-7

Every individual has two copies (alleles) of the TCF4 gene – one on each chromosome; a genetic change in just one of the copies can result in Pitt-Hopkins syndrome (autosomal dominant condition).

For most individuals with Pitt-Hopkins syndrome, their genetic change in the TCF4 gene occurs randomly (de novo) prior to birth and is not passed down (inherited) from their parents.⁶ In a very small number of reported families, the genetic change in one of the TCF4 alleles had been inherited from a parent who has the genetic change in some but not all of their cells (this is called genetic mosaicism), and often has typical learning and health.^2,3

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis

Diagnosis of Pitt-Hopkins syndrome may be considered based on signs and symptoms and confirmed by genetic testing.

Information about internationally recommended clinical diagnostic criteria for Pitt Hopkins syndrome can be found at Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement.

Genetic testing for Pitt-Hopkins syndrome may include chromosomal microarray analysis (CMA), exome or genome sequencing, gene-targeted testing or karyotyping, to identify changes in the TCF4 gene.^1,2

General information about these genetic tests can be found at:

• Pathology Tests Explained: Genome-wide chromosome microarray testing
• Pathology Tests Explained: Whole Genome or Whole Exome Testing for Childhood Syndromes

Differential diagnosis (to rule out other condition) includes Angelman syndrome, Rett syndrome and Mowat-Wilson syndrome.³

Please speak to your medical team to learn more about the available diagnostic pathways for Pitt-Hopkins syndrome.

Treatment

There is no curative treatment for Pitt-Hopkins syndrome, but there are strategies to manage the symptoms and improve quality of life. This involves a multidisciplinary medical team, and care is often life-long. Management strategies may include speech and language therapy, physiotherapy, occupational therapy, use of orthotics and assistive equipment as well as augmentative and alternative communication (AAC) tools and management of constipation.¹

Please speak with your medical team to learn more about suitable management strategies for Pitt-Hopkins syndrome. The strategies will depend on an individual’s specific symptoms.

Clinical Care

Healthcare professionals involved in the treatment of Pitt-Hopkins syndrome may include general practitioners (GP), paediatricians, geneticists, neurologists, gastroenterologists, pulmonologists, orthopedic specialists, ophthalmologists, audiologists, speech therapists, occupational therapists, physiotherapists, psychologists and psychiatrists.¹ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Research and Data

Please visit Australian Clinical Trials to learn about clinical trials for Pitt-Hopkins syndrome in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for Pitt-Hopkins syndrome in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Rare Disease Organisation(s)

There are currently no known organisations for Pitt-Hopkins syndrome in Australia. If you are aware of any relevant organisations in Australia, please let us know via the Contribute page.

International Organisations
Pitt Hopkins Research Foundation (PHRF) (based in United States)
Website: https://pitthopkins.org/

The mission of the Pitt Hopkins Research Foundation (PHRF) is to support research dedicated to finding a treatment, and an eventual cure for Pitt Hopkins Syndrome and other similar disorders. The PHRF is also dedicated to supporting the Pitt Hopkins community with resource recommendations, parental support and the latest medical information.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance.

Support Services/Resources

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

Mental Health

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful.

Information about relevant mental health and wellbeing support can be found at:

• RARE Portal: Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Other

Further information on Pitt-Hopkins syndrome can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Pitt hopkins syndrome
• National Organization for Rare Disorders (NORD): Pitt-Hopkins syndrome

References

1. Zollino M, Zweier C, Van Balkom ID, et al. Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement. Clin. Genet. 2019;95(4):462-478. https://doi.org/10.1111/cge.13506
2. Sweetser DA, Elsharkawi I, Yonker L. Pitt-Hopkins syndrome. 2012. Updated 12 April 2018. In: Adam MP, Mirzaa GM, Pagon RA, et al. GeneReviews® [internet]. Seattle (WA): University of Washington Seattle. 1993–. Accessed 18 March 2025. https://www.ncbi.nlm.nih.gov/books/NBK100240
3. Pitt-Hopkins syndrome. Updated February 2020. Accessed 18 March 2025. https://www.orpha.net/en/disease/detail/2896
4. Amiel J, Rio M, de Pontual L, et al. Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am. J. Hum. Genet. 2007; 80: 988-993. https://doi.org/10.1086/515582
5. Zweier C, Peippo MM, Hoyer J, et al. A. Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). Am. J. Hum. Genet. 2007; 80: 994-1001. https://doi.org/10.1086/515583
6. Online Mendelian Inheritance in Man (OMIM). #610954: Pitt-Hopkins syndrome; PTHS. Updated 29 July 2024. Accessed 18 March 2025. https://www.omim.org/entry/610954
7. Goodspeed K, Newsom C, Morris MA, et al. A review of current literature, clinical approach, and 23-patient case series. J. Child. Neurol. 2018 ;33(3):233-244. https://doi.org/10.1177/0883073817750490
8. National Organization for Rare Disorders (NORD). Pitt-Hopkins syndrome. Accessed 18 March 2025. https://rarediseases.org/rare-diseases/pitt-hopkins-syndrome

Page Last Updated

25/03/2025 02:31