Leigh syndrome, French-Canadian type (LSFC), is a rare and specific form of Leigh syndrome, which is a severe neurological disorder that typically presents in infancy or early childhood. Leigh syndrome is characterized by progressive neurodegeneration that affects the central nervous system, leading to developmental regression, movement abnormalities, and other neurological symptoms.
Leigh syndrome genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Leigh Syndrome, French-Canadian type (LSFC), include:
- Mitochondrial Dysfunction: Like other forms of Leigh syndrome, LSFC is associated with mitochondrial dysfunction, which impairs the energy-producing processes within cells.
- Onset and Progression: LSFC usually presents in infancy, and the symptoms progressively worsen. The rate of progression can vary among affected individuals.
- Developmental Regression: Children with LSFC experience developmental regression, meaning a loss of previously acquired developmental milestones. This may include loss of motor skills, language skills, and cognitive abilities.
- Movement Abnormalities: Individuals with LSFC may exhibit movement abnormalities such as hypotonia (low muscle tone), spasticity (stiff muscles), and ataxia (lack of coordination). These motor impairments can impact mobility.
- Seizures: Seizures are common in individuals with LSFC and can contribute to overall neurological dysfunction.
- Brainstem and Basal Ganglia Involvement: Neuroimaging studies, such as magnetic resonance imaging (MRI), often reveal abnormalities in the brainstem and basal ganglia. These regions are critical for motor control and coordination.
- High Incidence in the French-Canadian Population: LSFC is more prevalent in the French-Canadian population due to a specific genetic mutation identified in affected individuals. Mutations in the LRPPRC gene cause the disorder.
- Metabolic Acidosis: Some individuals with LSFC may develop metabolic acidosis, a condition characterized by an increased acidity in the blood.
There is currently no cure for Leigh syndrome, and management typically focuses on supportive care to address symptoms. Treatment may include physical and occupational therapy, seizure management, and nutritional support.
The prognosis for individuals with LSFC is generally poor, and the disorder can be life-limiting. Early diagnosis through genetic testing is essential for providing appropriate care and support to affected individuals and their families. Genetic counseling is essential for families with a history of LSFC to assess the risk of having affected children and to provide information about family planning options.
More Information
Leigh syndrome, French-Canadian type, is caused by pathogenic variants in the LRPPRC gene that encodes for a leucine-rich protein of the pentatrapine-peptide repeat (PPR) family that appears to be involved in the transport and stability of mature mitochondrial messenger RNA. It has been observed that all patients with this pathology have a deficiency in the enzyme cytochrome C oxidase, called COX, which is involved in the respiratory chain. The analysis of blood lactate levels, determining COX activity in fibroblasts, and identifying the c.1061C>T mutation in the LRPPRC gene helps diagnose the syndrome.
The c.1061C>T mutation (p.Ala354Val) produces a highly conserved amino acid change that affects the secondary structure of the protein. Functional studies indicate that this change affects protein trafficking in mitochondria. It has been found in patients in both homozygosis and compound heterozygosis (one copy of c.1061C>T combined with another mutation pathogenic in LRPPRC).
Leigh syndrome genetic testing analyzes the most frequent pathogenic mutation of the LRPPRC gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
