progressive supranuclear palsy-parkinsonism syndrome

Progressive supranuclear palsy-parkinsonism syndrome is an atypical variant of progressive supranuclear palsy, a late-onset neurodegenerative condition that primarily affects movement and eye control. It is associated with changes in the MAPT gene, which plays a critical role in regulating tau protein function in the brain. Most affected individuals develop symptoms during later adulthood, and the exact prevalence remains unknown. The condition is inherited in an autosomal recessive manner, meaning that two copies of the altered gene are typically required for the disease to manifest.

The clinical presentation is characterized by key neurological features, with abnormal saccadic eye movements, vertical supranuclear gaze palsy, and postural instability being highly common. Many individuals also experience parkinsonism with a favorable response to dopaminergic medication, along with dystonia, rigidity, falls, tremor, and bradykinesia. Cognitive issues such as mental deterioration, impaired visuospatial constructive cognition, memory impairment, and apathy can also occur, while additional features like abnormal speech patterns, axial muscle stiffness, neuromuscular dysphagia, and respiratory distress appear in a subset of patients. Not all individuals experience all features, and severity varies considerably.

The condition is linked to pathogenic variants in the MAPT gene, which encodes the microtubule-associated protein tau. Disruption in tau protein function can lead to abnormal protein accumulation and neuronal dysfunction. Inheritance is autosomal recessive, meaning that affected individuals inherit two copies of the altered gene, one from each parent. Genetic counseling is recommended for families to understand recurrence risks and the implications for family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Treatment is tailored to the individual's needs and typically involves a multidisciplinary team to address movement difficulties, cognitive changes, and other complications. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious, with specialists such as movement disorder experts and rehabilitation therapists providing guidance. Genetic counseling is also recommended so that patients and families can discuss available management options and plan for the future.

The course of progressive supranuclear palsy-parkinsonism syndrome is highly variable, with outcomes depending on symptom severity, age at diagnosis, and access to specialized care. Many individuals experience a gradual progression of motor and cognitive symptoms, although some patients may have a period of relative stabilization. With current standards of care, quality of life may be maintained for a period, and 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 this condition, and genetic counseling can provide valuable information about the risks and implications for family members. Severity and symptoms vary widely between individuals.

Several clinical trials are currently investigating new treatment approaches for progressive supranuclear palsy-parkinsonism syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.