Introduction

What is PURA syndrome?

PURA syndrome is a rare genetic syndrome that affects the nervous system and brain development. There are roughly 500 reported cases worldwide. It is caused by mutations in the PURA gene. This gene regulates the activity of brain cells.¹ These mutations can cause intellectual disability, developmental delays, and behavioural difficulties. More common symptoms may include hypotonia, metabolic abnormalities as well as epileptic seizures.¹ 

Although it is a rare disease, PURA syndrome has garnered attention in the medical industry due to the distinctive features it presents on the individual and the impact it has on their personal and familial lives. This article discusses the different aspects of the syndrome which are crucial for an accurate diagnosis and management.

Understanding intellectual disability

Intellectual disability (ID) involves an individual's struggles with general mental abilities.²  Intellectual functioning (learning and reasoning) and adaptive functioning (everyday tasks including communication and independent living) can be affected.² It is important to note that ID can occur due to various factors, including PURA syndrome, environmental factors, and prenatal circumstances, and can be diagnosed during childhood through cognitive, adaptive, and language assessments.

Causes and genetics

How PURA gene mutation leads to ID

PURA syndrome is caused by a genetic mutation in the PURA gene, located on chromosome 5. Researchers believe the mutations in the gene lead to cognitive impairments and disruptions in brain development. Furthermore, as the PURA gene is involved in neuron growth and gene expression, changes in how this gene functions can affect brain chemistry, development, and function.

How it is inherited

There is no specific way in which PURA syndrome is inherited in an individual. At times, it may be inherited in an autosomal dominant pattern, which means only one copy of the mutated gene is required to cause the condition. A child who has a parent with this mutated gene has a 50% chance of inheriting it. In other cases, the mutation may occur sporadically, meaning it has not been inherited from any parent and just occurs unexpectedly. Understanding the genetic basis of the syndrome is the key to accurately diagnosing symptoms presented as PURA syndrome. Genetic testing can confirm the diagnosis and provide information about how it may or may not be passed on to future generations.

Signs and symptoms

Developmental challenges

Individuals diagnosed with PURA syndrome experience challenges during their early life development that affect their growth and learning. These may include delays in walking, crawling, or more. A study found signs of motor delay in a child who was only 3 years old.³ Through evidence of further symptoms and tests, the child was diagnosed with PURA syndrome. Cognitive challenges were also evident in the child which would lead to difficulties in problem-solving, academic achievements, and more. Developmental challenges may further lead to behavioural issues within individuals. These may include autism spectrum disorder (ASD), difficulties in social interaction, communication, and sensory sensitivity. Further issues in behaviour may also include aggression and hyperactivity.

Associated health problems

Additional health problems can also be associated with PURA syndrome alongside behavioural and developmental challenges. Patients have exhibited breathing problems, gastrointestinal problems (feeding difficulties, constipation, and acid reflux), hypersomnolence (difficulty in falling asleep or staying awake), ophthalmological abnormality, and epilepsy.¹ 

Understanding the signs and symptoms associated with PURA syndrome is the key to early detection and diagnosis. Working alongside professionals with different specialities such as neurology, paediatrics, and psychology, is necessary, to address the complex needs of an individual with the PURA syndrome due to its rarity.

Diagnosis and evaluation

Identification and tests for PURA syndrome

Due to its rarity, the diagnosis of PURA syndrome is still a challenge to the medical world. Healthcare professionals have to consider the symptoms and clinical features discussed previously, alongside genetic testing, to reach the most accurate conclusion possible. Studying the medical and family history alongside the developmental achievements, is usually the first step in identifying whether an individual may have PURA syndrome.

Genetic testing is currently the gold standard in confirming the diagnosis of PURA syndrome. This involves sequencing the PURA gene to identify any variations or mutations that may have occurred. With the improvement of genetic testing, PURA syndrome diagnosis has increased.⁴ Genetic testing may be performed using a variety of methods, including chromosomal microarray analysis, whole exome sequencing, or targeted sequencing of specific genes. Additionally, imaging techniques such as MRI can be used to evaluate brain structure and identify any changes that may have been caused by PURA syndrome. 

Assessing developmental and behavioural aspects

Evaluating an individual’s developmental and behavioural aspects is also a key part of diagnosing PURA syndrome. Standardised tests evaluating cognitive, language, motor, and adaptive functioning, are one way to do so. Additionally, behavioural observations and screening tools may be used to assess for ASD traits and other behavioural concerns commonly associated with PURA Syndrome.

Management and treatment

A team-based approach to care

A team-based approach ensures that the diverse needs and difficulties individuals with PURA syndrome undergo can be addressed at the highest level. This would require multiple healthcare professionals of different backgrounds, including educators and support services.

Early intervention

Early intervention is crucial for maximising the developmental potential and improving outcomes for individuals with PURA syndrome. These strategies may include developmental therapy and educational programmes initiated at early stages of childhood. These interventions must be tailored towards each individual and may involve unique activities and guidance for the best possible outcome.

Medication and therapies

There is no specific treatment for PURA syndrome. Symptomatic treatment and rehabilitation therapy act as the primary treatment.⁴ Medication such as antiepileptic drugs and sleep medication may help control the symptoms. It can also reduce seizures and aid in sleep disturbances. Behavioural therapies, including applied behaviour analysis (ABA) and social skills training (SST), may help individuals with PURA Syndrome develop adaptive behaviours and improve social interactions.

Special support services play a therapeutic role in managing PURA syndrome that is away from medication. Special education programmes and support groups with individuals and families are some examples of these services. By addressing the needs of an individual with PURA syndrome, their quality of life can be managed at the highest level.

Summary

PURA syndrome is a rare genetic disorder, with only around 500 cases worldwide affecting brain development, and presenting with intellectual disability and behavioural issues. Although rare, it impacts the lives of the affected individuals. Understanding the basis of the disorder is crucial as just a mutation in the PURA gene can lead to these impairments in the patients. 

Symptoms include developmental and cognitive challenges and greater behavioural issues, such as autism. Further health issues such as epilepsy and digestive problems are also common. Diagnosis is also challenging. It requires the expertise of multiple healthcare professionals, alongside genetic testing, to correctly diagnose children as early as possible.

Managing the syndrome requires different healthcare professionals to work together in a team-based setting to provide the individual with the best-personalised treatment. Part of the management requires educational and behavioural therapies from an early age. There is yet no treatment for PURA syndrome, so long-term treatment requires planning and support to ease the lives of those diagnosed.