Leigh syndrome

Leigh syndrome is a progressive neurological disorder characterized by distinct brainstem and basal ganglia lesions. It is associated with pathogenic variants in the LRPPRC gene, which plays a crucial role in mitochondrial function and energy production. The condition typically presents in infancy or early childhood, and its exact prevalence is unknown. As with many neurodevelopmental conditions, the severity and spectrum of symptoms vary widely between individuals.

Individuals with Leigh syndrome commonly display global developmental delay, a cardinal feature observed in all affected individuals. After a period of apparently typical early development, affected children may experience a phase of developmental regression marked by loss of previously acquired skills, which can affect cognitive and motor abilities. In addition to these neurodevelopmental challenges, the neurological involvement is underscored by characteristic findings such as gliosis on neuropathological examination. Not all individuals experience every feature, and the severity of symptoms can vary considerably.

Leigh syndrome is linked to pathogenic variants in the LRPPRC gene. The LRPPRC gene is critical for proper mitochondrial function, and its disruption interferes with the cell’s ability to produce energy efficiently. The condition can be inherited through mitochondrial as well as autosomal recessive patterns, meaning that in the autosomal recessive form, affected individuals inherit one mutated copy from each parent, while in the mitochondrial form, the mutation is passed from the mother. Families are encouraged to seek genetic counseling to understand the implications for recurrence and family planning.

Currently, management of Leigh syndrome focuses on supportive care and symptom management as there are no FDA-approved or foundational therapies specifically linked to this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team, which may include neurologists, metabolic specialists, physical and occupational therapists, among others. Patients and families are encouraged to discuss treatment options with their healthcare team and to consider genetic counseling for further guidance on management and family planning.

Leigh syndrome is a lifelong neurodevelopmental condition characterized by an initial phase of developmental delay and possible regression, followed by a period of relative stabilization in some individuals. With current standards of care, outcomes vary depending on symptom severity, age at diagnosis, and access to specialized interventions. Outcomes described in medical literature continue to evolve as standards of care improve, and it is important to recognize that the clinical course can range from stabilization to later motor decline. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for additional guidance.

Several clinical trials are currently investigating new treatment approaches for Leigh syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility and ongoing research opportunities.