Introduction

PURA syndrome is an extremely rare genetic disorder that causes issues with the nervous system. It is present at birth and triggers neurodevelopmental issues. The root cause of this disorder is due to a mutation in the PURA gene. This gene provides instructions for making a protein called pur-alpha, which helps nerve cells develop and function properly. As a result, damage to this gene can affect how the nervous system and the brain work.¹ Children with this condition often experience learning disabilities and developmental delays, which can vary in severity. Some newborns may have trouble feeding or breathing, while older children may struggle to learn to walk. Most individuals with PURA also experience seizures or seizure-like movements.²

Monitoring milestones in infants is paramount to support healthy growth and identify any concerns early. Neurodevelopmental and physical growth usually follow a predictable pattern, which makes it easier for parents and doctors to monitor progress. When milestones are delayed or missed, it can be a sign of a developmental issue. In conditions like PURA syndrome, delays in reaching motor milestones are often one of the first signs of the disorder.³ The purpose of this article is to assess the impact of PURA syndrome on motor milestones in infants, specifically sitting, crawling and walking.

Overview of motor milestones in typical development

For a baby to learn how to sit, crawl, and walk, they need to build strength, develop sensory awareness, and have a well-coordinated brain function. Each motor milestone lays the foundation for the next, gradually enhancing strength, coordination, and sensory development. The timing of these milestones can vary among babies, but generally, most begin to sit between 6 and 8 months, start crawling around 8 months, and are walking by about 18 months of age.⁴ For any individual, these motor skills are developed through an awareness of their own body and their environment. This process relies on several sensory systems: the vestibular system, which helps babies maintain orientation; vision, which allows them to see if they are sitting straight or leaning to one side; and the somatosensory system, which helps them perceive touch and pressure.⁵ The neuromuscular system (responsible for the coordination of the nervous and muscular system) also plays a key role in motor control. It involves the brain sending signals through motor neurons to muscles, triggering contraction and relaxation phases that produce movement.⁶ When an infant reaches these key motor milestones, it often reflects healthy social, cognitive and sensory development. Socially, achieving these milestones allows children to interact and play with other children of a similar age group, helping them build friendships and social connections, which is an important part of growing up. Reaching these motor milestones also indicates good sensory development, which is vital for all individuals. It helps alert the body to potential danger by triggering the fight-or-flight response, supports concentration, and aids in interactions with objects and other people.⁷ Cognitive development, in turn, reflects good mental health and the brain’s ability to carry out both conscious and unconscious functions.

PURA syndrome symptoms

The symptoms of PURA syndrome are wide-ranging and can vary depending on the individual’s age and condition.

In newborns, common symptoms include:

• Trouble with feeding or breathing
• Difficulty swallowing breast milk or formula (dysphagia)

In older children, symptoms may include:

• Unable to walk properly
• Poor motor skills
• Understanding language but struggling to speak
• Using only short words or simple phrases to communicate

Symptoms that can affect individuals of all ages include:

• Bone and joint issues
• Breathing problems (sleep apnea)
• Hypothermia
• Hypersomnia
• Eye problems, such as being cross-eyed
• Frequent hiccups
• Gastrointestinal tract issues, such as constipation
• Loss of muscle tone
• Unsteady balance or walking
• Vision problems
• Heart defects
• Vitamin deficiency
• Early puberty
• Urinary and reproductive organ problems

As briefly mentioned in the introduction, the PURA syndrome is caused by a mutation in the PURA gene, which affects brain development. The brain, as the command centre of the nervous system, is responsible for thoughts, memory, movement, and emotions through its complex functions. Any malfunctions or abnormalities in the brain can cause lots of subsequent issues, including the symptoms seen in PURA syndrome.⁸

Impact on specific milestones

Sitting is one of the earlier milestones a child completes before moving on to more milestones such as crawling and walking. To be able to sit, the abdomen, back, and hip muscles should be sufficiently developed for a baby to sit up whilst also having good balance. For most babies, tummy time helps build core muscles and develop motor skills, which eventually lead to sitting up independently. However, children with PURA syndrome often face problems with balance and muscle development, making tummy time more difficult for them.⁹

Building on this, crawling can be particularly challenging for children with PURA syndrome as it requires strong core, back, and hip muscles. Crawling serves as an important transitional stage between sitting and walking, helping prepare a child for independent walking. There are two common types of crawling: army crawlingwhere a baby uses their arms to pull themselves forward, and hands-and-knees crawling, which requires greater balance, cross-body coordination and spatial awareness. Many children with PURA syndrome may skip the traditional crawling stage or replace it with alternative movements, such as bum shuffling, due to difficulties with coordination and spatial awareness.¹¹

Only about 48% of patients with PURA syndrome can walk independently, and this milestone is often reached with a delay. Even when walking is achieved, it may appear abnormal, characterised by ataxic (uncoordinated), broad-based steps, or toe walking. Similar to challenges with sitting and crawling, these difficulties are due to hypotonia (low muscle tone) and muscle weakness, which make walking movements hard to perform. Walking is the most balanced and muscle-intensive of the three key motor milestones, making it the hardest for individuals with PURA syndrome to achieve. The inability to walk can subsequently impact social and emotional development, which are essential for overall character growth.¹²

Intervention and management strategies

Unfortunately, there is no current cure for PURA syndrome, so management focuses on reducing risks and improving quality of life, such as preventing complications like scoliosis.

The first step in managing PURA is an accurate diagnosis, which can be challenging because its symptoms overlap with many other conditions. Genetic testing is essential to confirm a mutation in the PURA gene and establish a diagnosis. Since the disorder varies widely between individuals, understanding each person’s unique symptoms is important for creating a personalised care plan.

For example, newborns who have difficulty feeding or breathing may receive hospital support. Older children might benefit from speech and language therapy to improve communication, physical therapy to enhance mobility, or surgery to correct facial, heart, or skeletal issues. Mobility aids such as adaptive strollers, braces, or wheelchairs may also be used. Additionally, anti-seizure medications can help control seizures.

It is crucial that family members and caregivers are well informed about PURA syndrome to provide the best care at home and ensure appropriate treatment.

For example, newborns who have struggled with feeding or breathing may receive hospital support. Older children might benefit from speech and language therapy to improve communication, physical therapy to improve mobility, or surgery to correct facial, heart, or skeletal abnormalities. Mobility aids such as adaptive strollers, braces, or wheelchairs may also be utilised. Additionally, anti-seizure medications can help control seizures.

It is essential that family members and caregivers are well-informed about PURA syndrome to provide the best care and ensure appropriate treatment

Summary

PURA syndrome is a rare disorder with a wide range of different symptoms that affect individuals differently and at varying levels of severity. Symptoms like muscle weakness and poor balance make it difficult for infants to reach motor milestones at the typical age. These milestones require strong core, abdominal, and hip muscles, as well as spatial awareness and coordination between the upper and lower body. Delays in motor development can also affect social and emotional growth, which are important for overall character development.

The condition can significantly impact quality of life, often requiring family members and caregivers to adjust their lifestyles to provide support. Unfortunately, there is no cure for PURA syndrome. However, many treatment and management options are available, tailored to each individual’s symptoms. For motor skills, these may include physical therapy and supportive equipment such as strollers or wheelchairs.