PURA syndrome is a genetic, neurodevelopmental condition caused by genetic changes (variants) in the PURA gene on chromosome 5.¹ It is a congenital condition (present from birth) and is characterised by hypotonia (low muscle tone) at birth, feeding difficulties, excessive sleepiness (hypersomnolence), moderate-to-severe neurodevelopmental delay, abnormal nonepileptic movements and epilepsy.^1-6

Other symptoms include recurrent central and obstructive apneas (sleep disorder where individuals temporarily stops breathing), other respiratory and sleep issues, speech and language difficulties (most individuals are non-speaking), and constipation. PURA syndrome can also cause issues with bones and joints (including hips and spine), heart, blood vessels, vision, and body temperature, as well as hormone deficiencies and delayed puberty. Both males and females can be affected by PURA syndrome.^3,4

Synonyms: PURA-related developmental and epileptic encephalopathy; PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome; PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation; Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties; NEDRIHF.

PURA syndrome has also been referred to as PURA-related neurodevelopmental disorder, along with 5q31.3 deletion syndrome. Individuals with 5q31.3 deletion syndrome share some features of PURA syndrome as one copy of the PURA gene is lost due to the 5q31.3 deletion. However, individuals with 5q31.3 deletion syndrome may have more severe symptoms due to contributions from other genes impacted by the deletion.¹

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA: 438213 PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

There is no known ICD:11 classification.
ICD-10:G40.4 Other generalized epilepsy and epileptic syndromes

Symptoms of PURA syndrome vary between individuals.³

Symptoms often present from birth or early childhood. Early symptoms include hypotonia (low muscle tone) from birth, feeding and swallowing difficulties (dysphagia), breathing (respiratory) challenges and sleep issues.^1,5 Aspiration pneumonia due to hypotonia and dysphagia has also been reported.¹

People with PURA syndrome have moderate to severe intellectual disability and difficulty communicating (i.e., speech and/or language conditions). Other symptoms can include movement disorder, excessive hiccups, issues with eyes and vision, and constipation.^1-6 

There may also be other features such as hip dysplasia, scoliosis, abnormalities with heart and blood vessels, hormone deficiencies and delayed puberty. Bone density and serum vitamin D levels can be low, with osteopenia or osteoporosis reported.¹

In PURA syndrome, epilepsy is common, and an individual may experience more than one type of seizure over time.¹ A seizure is a single episode caused by abnormal electrical activity in the brain.⁷ Epilepsy is the medical condition defined by a tendency to have recurrent, unprovoked seizures.⁷ Seizures can first occur at a wide range of ages, from the newborn (neonatal) period through to early adulthood.¹ If epilepsy develops, seizures may be frequent and can be difficult to control.

Most individuals with PURA syndrome are non-speaking.¹ This means that speech (i.e., the ability to produce speech sounds) is significantly impacted or not used at all. Some people who are non-speaking have better receptive language skills compared to expressive language skills (which means they may be able to understand more than they can communicate), however both can be significantly impacted.

Please speak to your medical team to learn more about the symptoms and health implications of PURA syndrome.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

PURA syndrome is a genetic condition. It is caused by disease-causing genetic changes in the PURA gene on Chromosome 5.^2,4 These genetic variants damage the pur-α protein, which is important for normal brain development.⁶

All individuals have two copies of the PURA gene – one copy inherited from each parent. PURA syndrome is an autosomal dominant condition, which means that having a genetic variant in just one of the PURA gene copies can result in PURA syndrome.

For most individuals with PURA syndrome, their genetic variant in the PURA gene occurs randomly in them and is not passed down from one of their parents. In a very small number of reported families, the genetic variant has been passed down from a parent who has the genetic change. This change may be in all or some of their cells (this is called genetic mosaicism); the parent may be mildly affected or unaffected (has typical learning abilities and health).^1,8More information on genetic mosaicism can be found at Centre for Genetics Education: Mosaicism.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a clinical geneticist or genetic counsellor. Clinical geneticists or 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

There are no formal clinical diagnostic criteria published for PURA syndrome.¹

Diagnosis of PURA syndrome may be suspected based on clinical characteristics and must be confirmed by genetic testing.

It has been suggested that a diagnosis of PURA syndrome should be considered in infants with characteristics such as hypotonia (weak muscle tone), feeding issues and respiratory difficulties, with or without seizures.⁵ As part of the diagnostic process, doctors may rule out other conditions that have similar symptoms (differential diagnosis), such as central hypoventilation syndrome, spinal muscular atrophy, cerebral palsy, myotonic/muscular dystrophy, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Pitt-Hopkins syndrome, Glut1 deficiency syndrome, nonketotic hyperglycinemia, and neurotransmitter disorders.

Please speak to your medical team to learn more about the available pathways for diagnosis of PURA syndrome.

There is currently no curative treatment for PURA syndrome. Treatment is targeted at managing symptoms and involves a multidisciplinary care team. This may include physiotherapy, occupational therapy, speech and language therapy, neurology care including epilepsy management with anti-convulsant medications, Vitamin D supplements, and management of heart and urogenital defects.¹

There are no specific guidelines for seizure management in individuals with PURA syndrome.  Seizures may be difficult to control or drug resistant, and management may require trialling different antiseizure medications alone or in combination. Regular review by epilepsy specialists is important to help manage symptoms and adjust treatments as needed. The efficacy of vagus nerve stimulation, ketogenic diet and cannabidiol has not been established. As the genetic variant involves all of the brain, there is no role for epilepsy surgery. Video EEG monitoring may be required to distinguish epileptic from non-epileptic abnormal movements (such as nonepileptic exaggerated startle response that can be very common in PURA syndrome).¹

A high proportion of individuals with PURA syndrome are non-speaking, and so other means of communication should be supported early and throughout life with a speech pathologist. The use of augmentative and alternative communication (AAC) has proven beneficial in some children with PURA syndrome,¹ especially when implemented early and consistently with families and clinicians. An AAC assessment should be completed with a speech pathologist.

Individuals may also be monitored, and treated accordingly, for constipation, musculoskeletal complications (such as hip dysplasia and scoliosis), osteoporosis, sleep disturbances, eye or vision issues, and hormone deficiencies.^1,4

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of individuals with PURA syndrome may include general practitioners (GP), developmental paediatricians, geneticists, genetic counsellors, neurologists, endocrinologists, respiratory physicians, ophthalmologists, orthopaedic surgeons, occupational therapists, physiotherapists, and speech therapists. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

PURA Foundation Australia: Families has information about the PURA clinical care network that consists of clinicians within Australia and New Zealand who assist PURA Foundation Australia in supporting PURA families and educating institutions and other clinicians about PURA syndrome.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for PURA 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 PURA syndrome experts (including Australian experts).

• GeneReviews®: PURA-Related Neurodevelopmental Disorders includes recommendations on evaluations, treatment, management and surveillance, based on experience of individuals with PURA syndrome; published in 2017 and updated in 2026.
• OrphanAnesthesia: Anaesthesia recommendations for PURA syndrome ; please note this was last modified in 2019.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with PURA syndrome at emergency departments or in other hospital services. They:

• Will need 24/7 attendant/carer support in emergency and hospital settings, regardless of age.
• Will not be able to communicate with spoken words and may use alternative communication methods such as Key Word Sign, sign language, or Augmentative and Alternative Communication (AAC) tools and devices. These must be available at all times.
• May have stronger receptive communication skills (ability to understand information) than expressive communication skills (ability to produce language).
• May have seizures and/or movement disorder.
• May require hoist access for transfers.
• May have feeding difficulties and continence issues.
• May present with myopathy as well as other neuromuscular abnormalities.
• May experience difficult IV cannulation and benefit from ultrasound guidance.
• May have orthopaedic metalware that should be considered before imaging scans.
• May have sensory issues such as hypersensitivity (over-responsiveness) or hypo-sensitivity (under-responsiveness) to sensory input, which can manifest as reactions to loud noises, touch, or bright lights.

PURA Foundation Australia: Research provides information about national and international research relevant to PURA syndrome in Australia.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

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

Australian Organisation:
PURA Foundation Australia
Website: https://www.purafoundation.au/
The PURA Foundation Australia is a non-profit charitable organisation, that has been established to provide national and local support systems for individuals diagnosed with PURA syndrome and their families, across Australia and New Zealand. The Foundation funds pioneering research, provides support and education for families, and advocates for improved care and treatment for PURA syndrome.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

PURA syndrome varies between individuals, and each person’s experience is unique.

PURA Foundation Australia: Community contains personal stories from families living with PURA syndrome.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

PURA Foundation Australia: Community has information about support for parents and families of children with PURA syndrome. This includes dedicated parent support information offering peer support, sharing lived experience, links to government supports and help so families feel informed, supported, and less alone on their PURA journey.

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.

People living with a rare disease 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 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:

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

Further information on PURA syndrome can be found at:

• Genetic and Rare Diseases (GARD) Information Center: PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation
• National Organization for Rare Disorders (NORD): PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation
• Unique (Understanding chromosome disorders): PURA and 5q31 deletion syndrome

GeneReviews®: PURA-Related Neurodevelopmental Disorders

Online Mendelian Inheritance in Man, OMIM®:#616158 Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties; NEDRIHF

Orphanet: PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with the PURA Foundation Australia,

• Mel Anderson (PURA Foundation Australia – Director and Chair)
• Professor Michael Hildebrand (Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Victoria, Australia)
• Professor Richard Leventer (Department of Neurology, Murdoch Children’s Research Institute, The Royal Children’s Hospital Melbourne, Victoria, Australia)
• Dr Miya St John (Translational Centre for Speech Disorders, Murdoch Children’s Research Institute, Melbourne Victoria, Australia).

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.