neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures

Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures is an extremely rare condition, affecting fewer than 1 in 1,000,000 people. It is caused by pathogenic variants in the IRF2BPL gene, which plays a key role in normal neurological development. The disorder is inherited in an autosomal dominant manner, meaning a single altered copy of the gene can lead to clinical manifestations. Affected individuals typically present in early childhood with core features such as seizures, absent speech, and intellectual disability, along with a range of motor and neurological challenges.

The clinical presentation of this condition is striking, with seizures, absent speech, and intellectual disability being consistently observed in all affected individuals. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Over time, many individuals develop additional neurological and motor symptoms such as loss of ambulation, dystonia, and ataxia, which can significantly impact mobility and coordination. Some patients may also experience difficulties with swallowing (dysphagia), visual alignment issues like esotropia, hyperreflexia, and signs such as a positive Babinski reflex along with evidence of cerebellar or cerebral atrophy. Not all individuals experience all features, and severity varies considerably.

This condition is linked to pathogenic variants in the IRF2BPL gene. The IRF2BPL protein is believed to be important for normal brain development and function, and disruption in its activity leads to the constellation of neurological and motor symptoms observed in affected individuals. It is inherited in an autosomal dominant pattern, meaning that the presence of a single altered copy of IRF2BPL is sufficient to cause the disorder. Because autosomal dominant inheritance can occur sporadically, genetic counseling is recommended to help families understand potential risks and implications for future family planning.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. A multidisciplinary team—often including neurologists, rehabilitation specialists, and other healthcare professionals—develops an individualized care plan tailored to the patient’s needs. Long-term management involves regular surveillance to monitor for complications such as worsening motor function or swallowing difficulties, which helps in planning timely supportive interventions. Genetic counseling is also recommended to address recurrence risks and to guide families on available management options. Patients are encouraged to discuss treatment and care strategies with their healthcare team to determine the most appropriate approach for their specific situation.

This is a lifelong neurodevelopmental condition characterized by an initial regression, followed by a period of relative stabilization and, in some individuals, later motor decline. With current standards of care, many individuals experience improvements in quality of life, although the overall course of the disorder can vary significantly. Severity and symptoms vary widely between individuals, and outcomes depend on factors such as the degree of developmental regression, symptom severity, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists who are familiar with neurodevelopmental disorders for ongoing support and guidance.