childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder

Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder is a severe neurodevelopmental condition that primarily affects brain structure and function. A pathogenic variant in the UBTF gene, which plays a critical role in ribosomal RNA synthesis, underlies this disorder. Affected children typically develop normally for a period before experiencing significant loss of previously acquired skills. The condition is very rare, affecting fewer than 1 in a million people, and follows an autosomal dominant inheritance pattern.

The clinical presentation is marked by profound intellectual disability, cerebral atrophy, and a range of motor difficulties. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, including the loss of speech and motor abilities. Neuroimaging typically shows hyperintensity of cerebral white matter and atrophy of key brain structures such as the cerebrum and cerebellum. Other common features include hypoplasia of the corpus callosum, spasticity, ataxia, and dystonia, while some individuals may also exhibit seizures, parkinsonism, chorea, and rigidity. Not all individuals experience all features, and severity varies considerably.

This condition is caused by a pathogenic variant in the UBTF gene, which is integral to the production of ribosomal RNA and normal cellular function. Inherited in an autosomal dominant manner, a single copy of the altered gene is sufficient to cause the disorder. This means that an affected individual has a 50% chance of passing the variant on to each child. Genetic counseling is recommended to help families understand the implications, explore family planning options, and discuss the possibility of de novo cases where there may be no family history.

Currently, management focuses on supportive care and symptom management since there are no approved treatments specifically linked to this condition. A multidisciplinary team is typically involved in care, addressing the motor, cognitive, and communication challenges through therapies such as physical, occupational, and speech therapy. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation, and genetic counseling is recommended to guide families through care decisions.

This condition is a lifelong neurodevelopmental disorder characterized by an initial period of typical development followed by a regression phase, and in some individuals, later motor decline. With current standards of care, many individuals benefit from interventions that help stabilize or modestly improve symptoms, although outcomes vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists experienced in managing complex neurodevelopmental conditions and to seek genetic counseling for ongoing support.

There is an active clinical trial exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.