developmental and epileptic encephalopathy, 66

Developmental and epileptic encephalopathy, 66 is a neurodevelopmental condition characterized by early onset seizures and global delays in cognitive and motor skills. The disorder is associated with pathogenic variants in the PACS2 gene, which plays a role in cellular signaling and developmental pathways. It typically presents in infancy with seizures, delayed speech, and intellectual disability, and precise prevalence estimates are not well established. Although the condition is inherited in an autosomal dominant pattern, the clinical presentation can vary considerably between affected individuals.

Patients with developmental and epileptic encephalopathy, 66 most commonly present with intellectual disability, persistent seizures, and global developmental delay, all of which are always observed. Early signs include delayed speech and language development, with many children also exhibiting additional neurological features such as motor stereotypy and hypotonia. Other features that can be observed in a subset of individuals include specific facial features such as thin upper lip vermilion, hypertelorism, and downturned corners of the mouth, as well as focal-onset and bilateral tonic-clonic seizures. Not all individuals experience all features, and severity varies considerably.

The underlying cause of this condition is linked to changes in the PACS2 gene, which is vital for normal cellular functioning. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene can lead to the disorder. This inheritance mechanism implies that affected individuals have a 50% chance of passing the variant to their children, and genetic counseling is recommended to discuss the implications for family planning.

Currently, management focuses on supportive care and symptom management, as there are no established foundational therapies or FDA-approved treatments for this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team that may include neurologists, developmental pediatricians, and therapists. Regular surveillance is an essential part of long-term care, helping to identify and manage complications early. Families are encouraged to seek genetic counseling and work closely with specialists to explore all available supportive interventions.

The long-term outlook for individuals with developmental and epileptic encephalopathy, 66 varies considerably, with outcomes influenced by the severity of seizures and developmental delays. With current standards of care, many individuals can experience improvements in quality of life through supportive interventions and regular monitoring. Outcomes described in medical literature continue to evolve as standards of care improve, and individual experiences differ widely. Families are advised to connect with genetic counselors and specialists to discuss ongoing management and support options.