PURA syndrome is a condition characterized by intellectual disability and delayed development of speech and motor skills, such as walking.
Expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech), and most affected individuals are unable to speak. People with PURA syndrome may learn to walk later than their peers; many are never able to walk. In infancy, affected infants have very weak muscle tone (hypotonia) and feeding difficulties. Problems with swallowing (dysphagia) can last throughout life. In addition, affected infants can be excessively sleepy (hypersomnolent), have a low body temperature (hypothermia), and have short pauses in breathing (apnea) or episodes of abnormally slow breathing (hypoventilation). These breathing problems usually go away after age 1.
Recurrent seizures (epilepsy) are also common in PURA syndrome. Seizures usually begin before age 5 with uncontrolled muscle jerks (myoclonus). Other types of seizures can develop, such as generalized tonic-clonic seizures, which involve loss of consciousness, muscle rigidity, and convulsions. In people with PURA syndrome, seizures are often difficult to control.
Other features in people with PURA syndrome can include abnormalities of the heart, eyes, urogenital tract, gastrointestinal tract, and skeleton. Some affected individuals have symptoms of a hormonal problem, such as early sexual development (precocious puberty) or low levels of vitamin D (which is a hormone).
PURA syndrome is a rare condition affecting at least 70 individuals. It is estimated to account for fewer than 1 percent of cases of developmental delay.
PURA syndrome is caused by mutations in the PURA gene, which provides instructions for making a protein called Pur-alpha (Purα). This protein has multiple roles in cells, including controlling the activity of genes (gene transcription) and aiding in the copying (replication) of DNA. The Purα protein is especially important for normal brain development. Purα helps direct the growth and division of nerve cells (neurons). It may also be involved in the formation or maturation of myelin, the protective substance that covers nerves and promotes the efficient transmission of nerve impulses.
Mutations in the PURA gene are thought to lead to a reduced amount of functional Purα protein. Although it is not understood how a partial loss of Purα function leads to the signs and symptoms of PURA syndrome, researchers suspect that it may alter normal brain development and impair the function of neurons, leading to developmental problems and seizures in people with the condition.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Most cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.