PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome is a very rare neurologic disorder that primarily affects infants, presenting with profound low muscle tone, global developmental delay, feeding difficulties, and episodes of seizures or seizure-like activity. The condition is associated with pathogenic variants in the PURA gene, which is crucial for normal brain development and function. Although symptoms are evident from the neonatal period, the severity and specific features vary significantly among affected individuals. Overall, this disorder is exceptionally uncommon, affecting fewer than 1 in 1,000,000 people.

The clinical presentation is predominantly neurological, with key features including neonatal hypotonia, significant developmental delays, and intellectual disability. Affected individuals often experience seizures or seizure-like episodes, which along with feeding difficulties and visual abnormalities such as strabismus, underscore the multisystem involvement of this condition. Other frequently reported features are delayed fine motor development, a broad-based gait, and respiratory irregularities, all of which contribute to a complex clinical picture. Not all individuals experience every symptom, and variability in the cognitive and developmental impact is well recognized.

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome is caused by pathogenic variants in the PURA gene. This gene produces a protein that is critical for neuronal development and regulation, and disruption in its function is believed to lead to the neurologic and systemic manifestations observed in affected individuals. The available data do not specify a clear inheritance pattern, so the genetic basis remains primarily defined by the presence of alterations in PURA. Given the complexities of genetic contributions, genetic counseling is recommended to help families understand the implications of a variant in this gene.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Treatment is highly individualized and typically involves a multidisciplinary team that includes physical, occupational, and speech therapists. Long-term care includes regular surveillance and monitoring to address respiratory, feeding, and developmental challenges as they arise. Patients should discuss available treatment options with their healthcare team, and genetic counseling is recommended to assist in family planning and ongoing management decisions.

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome is a lifelong condition with a highly variable course. Many individuals face substantial developmental and neurological challenges, yet the progression can range from periods of relative stability to later motor decline in some cases. Outcomes described in medical literature continue to evolve as standards of care improve, and individual experiences differ considerably. Families often find it helpful to connect with specialists familiar with this condition and to seek guidance from genetic counselors for ongoing support and management.