CLN2 Disease
What is CLN2 Disease?
CLN2 disease is a type of Batten disease. Batten disease is a group of genetic conditions which cause neurodegeneration.1 CLN2 disease may be referred to as Late infantile Batten disease. Batten disease might also be known as Neuronal Ceroid Lipofuscinosis (NCL).
CLN2 disease is a type of childhood dementia which is autosomal recessive. Autosomal recessive means that individuals need two variants in both copies of the gene. In the case of CLN2 disease, individuals have a variant in each copy of the TPP1 gene. The TPP1 gene creates an enzyme called tripeptidyl peptidase 1 (TPP1). The TPP1 enzyme plays an important role for breaking down and recycling waste in the nervous system.
Classical CLN2 disease is the most common form of CLN2 disease. Atypical CLN2 disease often shows a slower disease course than classical CLN2 disease. The information is on classical CLN2 disease.
Many individuals with CLN2 disease will receive enzyme replacement therapy (ERT) through a port in their head or in their chest. ERT helps replace the missing TPP1 enzyme, which slows disease progression but does not cure CLN2 disease.2
Contact
For further information, do get in touch with the CRE Speech and Language team at:
Email: geneticsofspeech@mcri.edu.au
Phone: (03) 9936 6334
Frequently asked questions
- Epilepsy: individuals experience seizures which can become harder to control with medication.1,2,4
- Vision: individuals with CLN2 disease gradually lose their vision.1,2,4
- Motor disorders: many individuals seek support from occupational and physiotherapists. Individuals lose motor skills and require assistance to move around (e.g., a wheelchair).1,2,4
- Feeding difficulties: individuals often requiring enteral feeding (e.g., a G-tube) in the later disease stages.1,4
- Intellectual disability: individuals experience cognitive decline.1,2,4
- Sleep disturbances and behavioural difficulties.1,4
Many individuals with CLN2 disease will say their first words at an age like that seen in typical development (12 months).3,4 However, individuals often exhibit delayed milestones when learning to combine words to create sentences. Some individuals may never learn to combine words to create sentences. Most children with CLN2 disease will show speech and language ‘delay’ before they receive a genetic diagnosis of CLN2 disease.3,4
As the disease progresses, individuals experience changes in speech and language skills. Speech changes include speech becoming more difficult to understand due to a neuromuscular speech disorder called dysarthria. Language changes include losing symbolic communication skills, such as using words and gestures to commmunicate.4 Individuals with CLN2 disease will usually end up losing all speech.
Due to the progressive nature of CLN2 disease, individuals require an alternative way to communicate. Alternate ways to communicate are known as augmentative and alternative communication (AAC). AAC can include body movement, facial expression, on-body sign language, touch, and non-electronic (low-tech) and electronic (high-tech) communication aids.3,4 AAC should be implemented as early as possible alongside maintaining current speech and language skills for as long as possible. AAC should also be adaptive to loss of vision and motor skills. 4,5
Caregivers and support people around the child should be provided with communication partner training.6 Communication partner training may include strategies such as using simple language, breaking down instructions and tasks, using reminders and cues, providing choices, and using active listening strategies. Likewise, environmental supports should be considered to support an individual’s understanding (receptive language), reduce disorientation, and support social connection with others.7
Children who have early access to ERT will likely exhibit a different disease course, including different speech, language and AAC support needs, to children with later access to ERT. For example, children who had early access to ERT may present with slowed speech and language regression than children with later access to ERT.4 Some children may have access to ERT before they show features of CLN2 disease, for instance if they are diagnosed because their older sibling receives a diagnosis. Presently, we do not know much about how these children’s speech and language will look over time, but we do know that these children have stronger speech and language skills than children who receive ERT later. 4
- For information on speech and language abilities and CLN2 disease, please see our CLN2 Disease Fact Sheet
- For a Plain Language Summary of our recent research on CLN2 disease, please see our Plain Language Summary.
- Batten Disease Support and Research Associations:
o Australia and New Zealand: https://bdsraaustralia.org/
o United States: https://bdsrafoundation.org/
o United Kingdom: http://www.bdfa-uk.org.uk/
o Canada: https://canadiancln2.org/ & https://www.battendisease.ca/ - More information on Dysarthria: Dysarthria Fact Sheet
- More information on AAC: AAC Fact Sheet
References
1. Mole, S. E., Schulz, A., Badoe, E., Berkovic, S. F., de Los Reyes, E. C., Dulz, S., ... & Williams, R. E. (2021). Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients. Orphanet journal of rare diseases, 16, 1-19.
2. Schulz, A., Ajayi, T., Specchio, N., de Los Reyes, E., Gissen, P., Ballon, D., ... & Kohlschütter, A. (2018). Study of intraventricular cerliponase alfa for CLN2 disease. New England Journal of Medicine, 378(20), 1898-1907.
3. Nickel, M., Gissen, P., Greenaway, R., Cappelletti, S., Hamborg, C., Ragni, B., ... & Specchio, N. (2023). Language Delay in Patients with CLN2 Disease: Could It Support Earlier Diagnosis?. Neuropediatrics, 54(06), 402-406.
4. Morison, L.D., Whiteman, I.E., Vogel, A.P., Tilbrook, L., Fahey, M.C., Braden, R., Bredebusch, J., Hildebrand, M.S., Scheffer, I.E., Morgan, A.T. (2025). Speech, language, and non-verbal communication in CLN2 and CLN3 Batten disease. The Journal of Inherited Metabolic Disease. 48(1):e12838. https://doi.org/10.1002/jimd.12838
5. Burkhart, L. J., & Porter, G. (2006, December). Partner-assisted communication strategies for children who face multiple challenges. In Comunicación presentada en el Congreso de la ISAAC: Düsseldorf, Germany.
6. Folder, N., Power, E., Rietdijk, R., Christensen, I., Togher, L., & Parker, D. (2024). The effectiveness and characteristics of communication partner training programs for families of people with dementia: A systematic review. The Gerontologist, 64(4), gnad095.
7. de Azevedo, M. C. D., Charchat-Fichman, H., & Damazio, V. M. M. (2021). Environmental interventions to support orientation and social engagement of people with Alzheimer's disease. Dementia & neuropsychologia, 15(4), 510–523. https://doi.org/10.1590/1980-57642021dn15-040012
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