autosomal recessive spinocerebellar ataxia 7

Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is a childhood-to-adult onset neurological disorder that primarily affects the cerebellum, the part of the brain that coordinates movement and balance. It is caused by harmful changes (pathogenic variants) in the TPP1 gene, which provides instructions for an enzyme that helps cells break down proteins. Because two altered copies of the gene are required, the condition affects males and females equally. SCAR7 is very rare, occurring in fewer than one in a million people worldwide. Severity and symptoms vary widely between individuals.

SCAR7 mainly presents with neurological and eye-movement difficulties. Early signs often include an unsteady gait, clumsiness, and limb or truncal ataxia that make walking and fine motor tasks such as writing challenging. As the condition progresses, many individuals develop scanning or slurred speech (dysarthria) and postural tremor. Brain imaging commonly shows cerebellar atrophy, which correlates with worsening balance and coordination. Ocular findings are another hallmark. Constant involuntary eye movements (nystagmus) and difficulty initiating purposeful eye motions (oculomotor apraxia) are present in nearly all reported individuals. Some people experience hypermetric saccades, diplopia, or interruptions in smooth pursuit. Less common features can include impaired vibratory sensation, hyperreflexia, urinary urgency, or swallowing difficulties. Not all individuals experience all features, and severity ranges from mild unsteadiness to late-life wheelchair dependence.

SCAR7 results from pathogenic variants in the TPP1 gene. TPP1 encodes tripeptidyl peptidase 1, an enzyme that breaks down small protein fragments within cellular compartments called lysosomes. When the enzyme is deficient or non-functional, waste proteins accumulate, leading to dysfunction and shrinking of cerebellar neurons that control coordination and eye movements. The condition is inherited in an autosomal recessive pattern. This means an affected person has two altered copies of TPP1, one inherited from each parent, who are usually healthy carriers. Each pregnancy between two carrier parents has a 25 percent chance of resulting in an affected child, a 50 percent chance of producing a carrier child, and a 25 percent chance of producing a child with two working copies of the gene. Because SCAR7 is extremely rare, it is more likely to appear when parents share a common ancestor, which increases the chance that both carry the same rare genetic variant. Genetic counseling can help families understand carrier status, recurrence risks, and testing options for relatives and future pregnancies.

Currently, management focuses on supportive care and symptom management tailored to each person’s needs. Physical and occupational therapy help maintain mobility, improve coordination, and adapt daily activities. Speech therapy can address dysarthria and swallowing issues, while vision rehabilitation may assist with nystagmus-related difficulties. Mobility aids such as walkers or wheelchairs are introduced as needed to preserve independence. Long-term management includes regular surveillance to monitor neurological status and eye health. Periodic assessments by a multidisciplinary team—typically including neurology, physiatry, rehabilitation specialists, and ophthalmology—help identify emerging complications before they become serious. Because no FDA-approved disease-modifying therapies exist, families are encouraged to discuss investigational options and clinical trial participation with their care team. Genetic counseling remains an integral part of comprehensive management.

SCAR7 is generally slowly progressive. Many affected individuals retain ambulation for decades, while others may require a wheelchair later in life, reflecting the wide range of severity. Cognitive function is usually preserved, and life span can be near normal when complications are managed effectively. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with hereditary ataxias and to participate in patient registries that track long-term outcomes and facilitate research.

Clinical trials are underway exploring new treatment approaches, including possible enzyme-based and small-molecule therapies aimed at modifying disease progression. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their healthcare team about eligibility.