frontotemporal dementia and/or amyotrophic lateral sclerosis 1

Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 is a condition that primarily affects the brain and motor neuron systems, leading to cognitive and motor challenges. It is caused by pathogenic variants in the C9ORF72 gene. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the altered gene can increase the risk of developing symptoms. Prevalence estimates are not well established, and not every individual with the mutation will develop all features of the condition.

The clinical presentation of frontotemporal dementia and/or amyotrophic lateral sclerosis 1 can vary considerably between individuals. Among the features that have been observed in some cases is supranuclear gaze palsy, which appears in about 5 to 29% of affected individuals. Patients may also experience changes in behavior, difficulties with language, and motor impairments reflective of both frontotemporal dementia and motor neuron disease, although the exact symptoms can differ from one person to another. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the C9ORF72 gene. The C9ORF72 gene plays roles in normal cellular functions, and alterations in this gene disrupt cellular processes, contributing to neuronal dysfunction in both the brain and motor systems. It is inherited in an autosomal dominant pattern, so a single altered copy of the gene from an affected parent can increase an individual’s risk. Genetic counseling is recommended to help families understand the implications of this inheritance pattern.

Currently, management focuses on supportive care and symptom management, with treatment tailored to each individual’s presentations. Since no FDA-approved treatments or foundational therapies have been established for this condition, care typically involves a multidisciplinary team to address cognitive, motor, and behavioral challenges. Patients are encouraged to discuss treatment options with their healthcare team, and genetic counseling is recommended to assist families in understanding the condition and planning for the future.

The course of frontotemporal dementia and/or amyotrophic lateral sclerosis 1 varies widely among individuals, with some experiencing a more rapid progression and others showing periods of relative stability. Outcomes depend on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals benefit from supportive treatments and multidisciplinary management, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists and genetic counselors to receive guidance and support regarding future care and family planning.