There are approximately 706 patients with PURA syndrome confirmed globally, across 60 countries, with 30 patients confirmed in Australia - New Zealand. To date there have been 317 different pathogenic (disease causing) variants of the PURA gene reported in public data. The p.Phe233del variant is the most common, with 45 cases confirmed so far, accounting for at least 6% of the patient population (PURA Foundation Australia, October 2024). With increased awareness and diagnostic testing, our numbers and community are growing.

What is PURA syndrome?

PURA syndrome is a rare neuro-developmental disorder. PURA syndrome is caused by pathogenic variants in the PURA gene. Located on Chromosome 5, the PURA gene is essential for the formation of pur-alpha, a protein which controls the activity of various genes (transcription), transport of different RNA molecules and generation of multiple proteins (translation), and is also vital for DNA replication.

These roles are critical for normal development of the brain by directing the growth, division and connection (synapse formation) of neurons (nerve cells), and the formation and maturation of myelin, a substance that protects nerves and promotes efficient nerve impulse transmission. PURA pathogenic variants often arise spontaneously (de novo), which means that they may appear for the first time in an infant without being present in any other family members. It has also been recently shown that in rare instances a parent with PURA syndrome may pass their PURA pathogenic variant on to their child.

Knowledge itself is power. #PURAawareness

Most common reported features of PURA syndrome.
Individuals with PURA syndrome have developmental delay, hypotonia and speech difficulties. Other common features include:

Feeding difficulties
Respiratory problems (including apneas)
Seizures and seizure-like abnormal movements
Movement disorder
Constipation
Orthopaedic issues including hip dysplasia and scoliosis
Vision issues
Delayed puberty
Endocrine disorders such as Vitamin D deficiency and kidney stones
Hypersomnolence (excessive sleepiness)
Excessive hiccups
Temperature instability

The differential diagnosis for PURA include:

Central Hypoventilation syndrome
Spinal Muscular Atrophy
Cerebral Palsy
Myotonic/Muscular Dystrophy
Prader-Willi syndrome
Angelman syndrome
Rett syndrome
Pitt-Hopkins syndrome
Neurotransmitter and Metabolic disorders

What is “5q31.3 deletion syndrome including PURA” and how is it related to PURA syndrome?

Sometimes spontaneous deletions can occur, removing a large segment of genetic material from a chromosome. Such deletions may remove many adjacent genes, depending on the exact size and chromosomal location of the deletion.

Deletions of the chromosome region we call ‘5q31.3’ can include loss of one copy of the PURA gene, as well as a variable number of other genes, depending on the size of the deletion. For this reason, the ‘5q31.3 deletion syndrome’ has overlapping features with PURA syndrome.

All individuals with 5q31.3 deletion described in the medical literature have very similar clinical features, but none has an identical chromosomal deletion. Broadly speaking, children with a 5q31.3 deletion have similar problems as individuals with PURA syndrome. However, individuals with a 5q31.3 deletion tend to be more severely affected. A likely explanation for this is that other neighbouring genes included in the 5q31.3 deletion may also be contributory. One gene that is usually included in this deletion and is suspected to have an important role is NRG2.

At the time of diagnosis, the following areas may be assessed by the patient’s medical team:

Developmental assessment
Genetic counselling
Feeding management and constipation assessment, if necessary
Respiratory studies, if necessary
EEG (measurement of brain’s electrical activity) if seizures are suspected
Brain imaging with MRI, if indicated
Eye examinations
Orthopaedic scans to check for hip dysplasia and scoliosis
Ultrasound scans of kidneys to exclude abnormalities and stones
Gynacology, endocrinology and hormone assessments if indicated
Vitamin D measurements
Bone density assessment if any specific concerns

Moving forward after the diagnosis, the following monitoring may be recommended by the patient’s medical team:

Long term follow-up by a developmental pediatrician (if child) and other medical specialists as required
Monitoring for constipation
Monitoring for musculoskeletal complications including hip dysplasia and scoliosis
Sleep study if apnea or sleep distrubances suspected
Referral for funding supports (Eg: NDIS if in Australia)
Speech and language therapy
Physiotherapy and occupational therapy
Regular eyesight checks may be recommended
Monitoring for puberty outcomes
EEG (measurement of brain’s electrical activity) if seizures are suspected

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