neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant is a condition marked by severe intellectual disability and significant motor impairments, including an inability to walk. It is caused by a mutation in the GRIN1 gene, which plays a crucial role in brain function and neural communication. Affected individuals typically present in early childhood with challenges in cognition, movement, and speech. While precise prevalence estimates are not well-established, the clinical spectrum shows considerable variability.

The clinical features primarily involve the central nervous system and motor functions. Affected individuals always exhibit severe intellectual disability and an inability to walk. Many also experience additional neurological and movement-related symptoms, such as stereotypical hand wringing, various forms of seizures (including focal impaired awareness and myoclonic seizures), and hypotonia. Other variable findings include features like microcephaly, cerebral atrophy, and specific facial traits such as a long face and deeply set eyes. Not all individuals experience all features, and severity varies considerably.

This condition is caused by a mutation in the GRIN1 gene, which encodes a critical component of the NMDA receptor involved in synaptic transmission and brain development. The mutation disrupts normal receptor function, thereby impairing key neurological processes. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene is sufficient to cause the disorder. Genetic counseling is recommended to help affected families understand recurrence risks and make informed decisions regarding family planning.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Therapy is tailored to the individual and involves a multidisciplinary team to address developmental delays, motor challenges, and associated neurological symptoms. Regular surveillance is an essential part of long-term care, helping to detect complications early and adjust interventions as needed. Genetic counseling is also recommended to offer guidance on family planning, and patients should discuss treatment options with their healthcare team to determine which strategies suit their specific situation.

This lifelong condition exhibits a highly variable course, with outcomes depending on the severity of neurological and motor impairments as well as access to specialized care. Although affected children face significant challenges due to severe intellectual disability and mobility limitations, many experience periods of stabilization following early developmental difficulties. With current standards of care, individualized management can improve quality of life, though the trajectory differs considerably among individuals. Severity and symptoms vary widely between individuals; families often find it helpful to connect with specialists familiar with this condition.