Introduction

PURA syndrome is a rare genetic disorder that affects the development and function of the nervous system. It is caused by mutations or deletions in the PURA gene located on chromosome 5. This condition often presents in infancy with symptoms such as severe muscle weakness (hypotonia), delayed development, feeding difficulties, and epilepsy. Since its identification as a distinct syndrome in 2014, increased awareness and improved genetic testing have led to more diagnoses and a clearer understanding of its genetic causes.¹

The primary purpose of this article is to provide a comprehensive, evidence-based explanation of how the PURA gene functions, how its alteration leads to the clinical features observed in PURA syndrome, and what is currently known about diagnosis and management. This explanation is supported by published research and clinical studies involving individuals with PURA syndrome.

Answering the main question

PURA syndrome results from changes, including deletions, in the PURA gene, located on chromosome 5 (region 5q31.3). This gene produces a protein called Pur-alpha, which is involved in the development of the central nervous system. Pur-alpha helps regulate how genes are expressed and supports the transport of messenger RNA (mRNA) inside brain cells (neurons), which is important for healthy brain function.² When the PURA gene does not work properly, it can disrupt brain development. This may lead to symptoms such as hypotonia, developmental delay, and epilepsy.³

Read on

To understand why this single gene can cause such a wide variety of symptoms, it is important to examine what the PURA gene does, how mutations affect the body, and how doctors diagnose and manage PURA syndrome. This article will also review recent research and the implications for families.

The location and function of the PURA gene

The PURA gene is located on chromosome 5q31.3 and spans a relatively small section of DNA. It produces Pur-alpha protein, which can bind to both DNA and RNA and is important for several critical cell functions. These include regulating the cell cycle, assisting in DNA replication, and controlling gene expression in neurons.⁴

In the brain, Pur-alpha plays an essential role during early development by helping to transport mRNA to the ends of neurons, where proteins are made. These proteins are needed for communication between neurons and for forming synaptic connections. Animal studies have shown that loss of this gene leads to severe brain development problems shortly after birth, which highlights its importance.⁵

How mutations or deletions lead to PURA syndrome

Most cases of PURA syndrome are caused by de novo mutations, which means they are new changes that occur in the child and are not inherited from the parents.⁶ These mutations are often either point mutations (single-letter changes in the DNA) or small insertions or deletions that disrupt the function of the gene. In other cases, larger deletions on chromosome 5q31.3 that include the PURA gene can also lead to the syndrome.⁷

These mutations usually result in a loss of function of the Pur-alpha protein. When this protein does not work properly, neurons struggle to grow, develop, or communicate effectively, which leads to the developmental and neurological symptoms seen in individuals with PURA syndrome.⁸ In some individuals, the condition is caused by a microdeletion syndrome, where a larger piece of DNA, including the PURA gene, is missing. These cases may be more severe depending on how many genes are involved.⁹

Clinical symptoms of PURA syndrome

While there is variability between individuals, most people with PURA syndrome present with a similar group of symptoms:

• Severe hypotonia, often evident at birth
• Feeding difficulties, such as weak sucking or swallowing
• Developmental delay, particularly affecting motor skills and speech
• Seizures, which may begin in infancy or early childhood
• Learning difficulties, typically in the moderate to severe range
• Sleep disturbances
• Poor temperature regulation or hypothermia
• Distinctive facial features, which may include a long philtrum or tented upper lip¹⁰
  

In some cases, individuals may also have visual impairments, scoliosis, hip dysplasia, or abnormal eye movements. The severity of symptoms can vary, even among those with similar genetic changes.¹¹

Diagnosis and testing methods

Due to the non-specific symptoms, PURA syndrome can be mistaken for other conditions. Diagnosis is usually confirmed through genetic testing, particularly whole-exome sequencing (WES), which examines the protein-coding regions of all genes in the genome. A chromosomal microarray can detect larger deletions involving the PURA gene.¹²

Testing is especially recommended when a child presents with severe hypotonia, feeding issues, and developmental delay without a clear cause. Early diagnosis can help families access supportive therapies and plan for long-term care needs.¹³

Management and support strategies

There is currently no cure for PURA syndrome; thus, management is directed at supportive treatment of symptoms and facilitating development in the child. The condition can affect several body systems; thus, treatment is best provided by a multidisciplinary team including paediatricians, neurologists, physiotherapists, occupational therapists, speech therapists, and nutritionists, all working together to meet the patient’s needs.¹⁴

Some general interventions include:

• Physiotherapy to improve muscle tone and motor development
• Speech and language therapy for communication difficulties
• Nutritional support, which can include gastrostomy feeding if necessary
• Medication to control seizures or reflux
• Orthopaedic treatment for scoliosis or joint problems

Assistive devices such as walkers or communication aids is also beneficial for some. Family psychological and emotional support is also required, especially since most children with PURA syndrome will require lifelong management.¹⁵

What research is telling us

The more patients diagnosed with PURA syndrome, the better researchers can know how some specific genetic changes relate to symptoms, a concept known as genotype-phenotype correlation. Recent research has indicated that individuals with larger deletions or truncating mutations (which cause the protein to stop forming too early) may have more severe motor and speech difficulties compared to those with smaller or less destrimental changes.¹⁶ 

Ongoing research is also exploring how Pur-alpha interacts with other proteins in the cell, which may help uncover new aspects of the disease. Animal studies are being used to investigate whether gene therapy or other targeted treatments could potentially benefit individuals in the future.⁵

Another important area of focus is genetic counselling, which is offered to families to explain the nature of the condition, the chances of it happening again, and the options available for prenatal testing. Although most cases are not inherited, a small number may result from germline mosaicism, where a parent carries the mutation in some reproductive cells. In such cases, there is a small but possible chance of recurrence in future pregnancies.¹⁷

FAQs

Is PURA syndrome inherited from parents?

In nearly all cases, the mutation occurs spontaneously and is not inherited from parents.⁶

Can PURA syndrome be detected before birth?

Prenatal testing is possible if there is a known PURA mutation in the family, although this is rare.¹⁷

What is the life expectancy for someone with PURA syndrome?

Life expectancy varies depending on severity and complications, but many individuals live into adulthood with proper medical care.¹⁴

Does PURA syndrome always cause seizures?

Not all individuals have seizures, but they are common and can vary in type and severity.¹⁰

Summary

PURA syndrome is a rare genetic disorder caused by mutations or deletions in the PURA gene, located on chromosome 5q31.3. This gene plays a crucial role in brain development, and when it does not function properly, it can lead to a range of developmental and neurological symptoms. Thanks to growing awareness and advances in genetic testing, earlier and more accurate diagnosis is now possible.

Although there is currently no cure, supportive care tailored to each individual’s needs can significantly improve quality of life. Ongoing research is helping scientists better understand how different genetic changes influence symptoms, and what potential treatments may become available in the future. Families benefit most from early diagnosis, access to a coordinated care team, and genetic counselling to help guide them through care and future planning. Growing awareness is helping to translate knwledge into action among individuals with PURA syndrome.