PURA syndrome is a rare neurodevelopmental disorder caused by a change in a single gene. First identified in 2014, this congenital disorder is present from birth and leads to a wide range of physical and intellectual difficulties. Families receiving this diagnosis often focus on the long-term outlook and their loved one’s quality of life.
The PURA Gene and Its Function
The underlying cause of this condition is a pathogenic variant in the PURA gene, which is situated on chromosome 5. This gene is responsible for providing instructions to make a protein known as Pur-alpha. Pur-alpha plays a significant role in the development and functioning of the brain.
The protein acts as a DNA- and RNA-binding molecule, controlling the activity of numerous other genes. This regulatory function is fundamental for the normal growth and division of neurons. A primary consequence of the gene change is haploinsufficiency, meaning that only one functional copy of the PURA gene remains.
Having only one working copy of the gene results in a reduced amount of the Pur-alpha protein, disrupting brain development. The lack of sufficient Pur-alpha impairs neuronal processes, including the formation and maturation of myelin, the fatty sheath that protects nerves. This disruption explains the profound neurological symptoms seen in individuals with the syndrome.
Major Health Complications
The diminished function of the Pur-alpha protein results in a complex array of health issues that can affect nearly every body system. One of the most common manifestations is profound intellectual disability and severe developmental delay. Most affected individuals experience significant difficulty with motor skills and communication, with many remaining nonverbal and unable to walk independently.
A defining feature is severe hypotonia, or low muscle tone, which is often present at birth and contributes to delayed motor milestones. This generalized weakness can also lead to orthopedic issues like scoliosis and hip dysplasia, requiring ongoing monitoring and intervention. Feeding difficulties (dysphagia) are frequent and often necessitate nutritional support through feeding tubes.
Epilepsy is another significant complication, affecting roughly half of all diagnosed individuals. Seizures typically begin in infancy or early childhood and can sometimes be refractory, meaning they are difficult to control with anti-epileptic medications. Affected newborns often experience breathing problems, such as apnea or hypoventilation, which may require respiratory support early in life.
Understanding Long-Term Prognosis
The long-term prognosis for PURA syndrome is still evolving, as the disorder was only first described in 2014. Consequently, there is a lack of long-term natural history data spanning multiple decades. PURA syndrome is classified as a neurodevelopmental disorder, not a degenerative one, which suggests a more stable outlook than conditions that progressively worsen over time.
Current observations indicate that survival into adulthood is the expected course for individuals with the syndrome, provided that complications are managed effectively. Many individuals diagnosed since 2014 are now adults, with some known patients living into their 50s. This longevity underscores that the disorder is compatible with a life extending well beyond childhood.
The factors that influence life expectancy are closely tied to the severity and management of the associated medical complications. Respiratory issues, particularly those related to central apnea and hypoventilation, can be life-threatening, especially in early life. Aggressive and consistent management of these breathing difficulties is paramount to improving the long-term outlook.
The control of seizures is a significant determinant of both quality of life and longevity. Individuals who experience refractory epilepsy face a higher risk of complications like status epilepticus. Managing nutritional status and preventing aspiration pneumonia due to chronic feeding difficulties are also major areas of focus. While there is no known cure, proactive, supportive care is the mechanism by which life is extended and quality of life is maintained.
Current Treatment Approaches
Management of PURA syndrome is supportive, focusing on addressing the specific symptoms experienced by each individual. This requires the coordinated effort of a diverse team of medical specialists, including neurologists, geneticists, pulmonologists, and orthopedic surgeons. Early intervention is a cornerstone of care to maximize abilities and mitigate secondary complications.
Developmental therapies are initiated early and continuously. Physical therapy focuses on improving muscle tone and mobility due to pervasive hypotonia and motor delays. Occupational therapy helps individuals develop fine motor skills and adaptive strategies for daily living tasks, while speech-language pathology addresses communication and swallowing difficulties.
Medical management includes anti-epileptic drugs to control seizures, though finding an effective regimen can be challenging. Nutritional support is provided for chronic dysphagia, and respiratory support may be necessary for breathing irregularities, especially in infancy. Surgical interventions may also be used to correct skeletal issues like scoliosis.