Neuronal Ceroid Lipofuscinoses type 6 (NCL6), also known as CLN6 disease, is a rare neurodegenerative disorder belonging to the Batten disease group. It is characterized by the abnormal accumulation of lipopigments in the cells of the nervous system and is caused by mutations in the CLN6 gene.
Neuronal ceroid lipofuscinoses type 6 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 neuronal ceroid lipofuscinoses type 6 (CLN6 disease) include:
- Onset: CLN6 disease typically begins in childhood, with the initial symptoms between 18 months and 8 years.
- Cognitive Decline: Progressive decline in cognitive abilities occurs, leading to intellectual disability.
- Motor Dysfunction: Individuals with CLN6 disease experience a gradual decline in motor skills, including coordination and balance.
- Seizures: Seizures are a common feature and may be one of the early signs of the condition.
- Visual Impairment: Vision loss is a characteristic feature, and affected individuals may experience difficulty with visual tasks.
- Speech and Language Regression: Speech and language skills loss may occur over time.
- Behavioral Changes: Changes in behavior, including irritability and aggression, may be observed.
- Movement Abnormalities: Some individuals may develop movement abnormalities such as tremors and myoclonic jerks.
- Brain Atrophy: Imaging studies may reveal progressive brain atrophy.
- Autosomal Recessive Inheritance: CLN6 disease follows an autosomal recessive inheritance pattern, meaning that affected individuals inherit mutated CLN6 genes from both parents.
The CLN6 gene provides instructions for making a protein involved in lysosomal function. Lysosomes are cellular structures responsible for breaking down and recycling various substances. Mutations in the CLN6 gene result in impaired lysosomal function, accumulating lipopigments, and subsequent cell damage in the nervous system.
There is currently no cure for CLN6 disease, and management is primarily supportive, focusing on symptom relief and improving the quality of life for affected individuals. Seizures may be treated with antiepileptic medications, and other supportive measures, such as physical and occupational therapy, may be employed.
Genetic counseling is essential for families affected by CLN6 disease to understand the inheritance pattern, assess the risk of having affected children, and discuss available reproductive options. Due to the progressive and debilitating nature of the condition, early diagnosis is crucial for initiating appropriate supportive care and interventions.
More Information
Neuronal ceroid lipofuscinosis type 6 is caused by mutations in the CLN6 gene that codes for neuronal ceroid lipofuscinosis protein 6, a transmembrane protein of the endoplasmic reticulum. It is unclear how alteration of this reticulum protein is related to lipofuscin accumulation in lysosomes. Still, it has been observed in animal models that CLN6 deficiency can alter the enzymatic composition of lysosomes.
The c.214G>T (p.Glu72Ter) variant in the CLN6 gene has been described in the homozygous state associated with late infantile latent neuronal ceroid lipofuscinosis. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation or mRNA decay.
Neuronal ceroid lipofuscinoses type 6 genetic testing analyzes the 4 most frequent pathogenic mutations of the CLN6 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).
