PURA syndrome is a rare neurodevelopmental disorder caused by a change in a single gene. This genetic disorder affects the development of the nervous system and multiple other body systems. First described in 2014, it is a relatively newly identified cause of intellectual disability. While considered very rare, with only around 750 to 800 individuals diagnosed worldwide, increasing awareness suggests the true prevalence may be higher. The disorder typically leads to widespread developmental delays, though symptom severity varies among affected individuals.
The Role of the PURA Gene
PURA syndrome is caused by a genetic change affecting the PURA gene, located on chromosome 5 (5q31.3). This gene provides instructions for creating the Pur-alpha protein, a versatile molecule expressed in almost all human tissues, including the brain, heart, and muscles. Pur-alpha acts as a DNA- and RNA-binding protein, giving it a regulatory role in several fundamental cellular processes.
Its functions include controlling the activity of many other genes (gene transcription), aiding in DNA replication, and transporting messenger RNA (mRNA) within nerve cells. In the brain, Pur-alpha is involved in the growth and division of neurons, the maturation of dendrites, and the formation of myelin, the protective sheath around nerve fibers.
The syndrome typically occurs when a person has a mutation or deletion in only one of their two copies of the PURA gene. This heterozygous mutation results in haploinsufficiency, where the body produces an insufficient amount of functional Pur-alpha protein. This reduction disrupts the normal development and function of neurons, leading to the neurological and developmental symptoms seen in the syndrome.
Common Physical and Developmental Characteristics
The clinical presentation is characterized by significant global developmental delay, often apparent early in infancy. Children commonly exhibit moderate to severe intellectual disability and delayed motor and speech development. Although most affected individuals have better receptive language skills (understanding) than expressive skills (speaking), many remain nonverbal throughout their lives.
A hallmark feature present from birth is early-onset hypotonia, or low muscle tone, giving infants a “floppy” appearance. This generalized weakness significantly impacts motor milestones, often delaying the ability to sit, crawl, and walk; many individuals never achieve independent walking. Hypotonia also contributes to feeding difficulties (dysphagia), which can require nutritional support and may persist into adulthood.
Movement disorders are common, including poor balance, an unsteady gait, and an exaggerated startle reflex. Infants often experience issues with temperature regulation, such as chronic hypothermia, and breathing irregularities like apnea (pauses in breathing) or hypoventilation (abnormally slow breathing). While breathing problems often lessen after the first year, temperature instability can remain a lifelong concern.
A majority of individuals develop epilepsy, with recurrent seizures often beginning before five years of age. Common seizure types include myoclonus (uncontrolled muscle jerks) and generalized tonic-clonic seizures, which are frequently difficult to manage with standard anti-epileptic medications. The syndrome also affects other bodily systems, leading to:
- Skeletal problems such as scoliosis (curvature of the spine) and kyphosis (hunching).
- Vision impairments, including strabismus (crossed eyes) and nystagmus (involuntary eye movements).
Establishing a Diagnosis and Supportive Management
A diagnosis is suspected based on characteristic clinical symptoms, particularly global developmental delay, hypotonia, and early-onset seizures. Because these symptoms overlap with other neurological conditions, differential diagnosis is employed to rule out disorders like Angelman syndrome or Prader-Willi syndrome.
Definitive confirmation requires genetic testing to identify the specific alteration in the PURA gene. Diagnosis is established using advanced genetic sequencing methods, such as whole exome sequencing or a targeted gene panel. These tests analyze the patient’s DNA to detect a pathogenic variant or a deletion of the 5q31.3 chromosomal region.
Since there is no cure, the primary approach to care is supportive and symptomatic, managed by a team of specialists. Early intervention with a range of therapies is initiated to maximize developmental potential.
Physical therapy focuses on improving muscle tone, strength, and coordination. Occupational therapy assists with fine motor skills and daily living activities. Speech and language therapy is crucial for communication development, often utilizing alternative methods for nonverbal individuals. Medical management includes anti-epileptic drugs to control seizures and nutritional support, such as feeding tubes, to manage swallowing difficulties.