Children with CLN2 disease

Signs & symptoms

Recognising the early signs

CLN2 disease should be suspected in children aged 2–4 years with new-onset, unprovoked seizures1

  • Unprovoked seizures commonly present in the majority of children with CLN2 disease between the ages of 2 and 42
    • For some children, the first seizure can be febrile in nature or onset may occur later3,4
  • Multiple types of seizures can be observed, including generalised tonic-clonic, absence, myoclonic, atonic, clonic and tonic4,5
  • Seizures continue over the course of the disease and become intractable, often requiring multiple anti-epileptic drugs6
  • Myoclonus – both epileptic and non-­epileptic – is the most predominant feature6

Children are often diagnosed with epilepsy without a further workup for CLN2 disease.1,6
Misdiagnosis can result in:

  • Treatment with anti-­epileptic drugs, with side effects that can mask and delay the recognition of CLN2 disease4
  • Tests delayed until the disease has significantly progressed1,6

Early language delay has been identified as a sign of CLN2 disease in the majority of patients7

83% of children with CLN2 disease experienced delay of early language development7

  • Criteria for identifying early language delay:8
    • First single words acquired at 18 months (or later/never)
    • First two-word sentences at 24 months (or later/never)
    • First full sentences at 36 months (or later/never)

Percentage of ‘late talkers’ in children with CLN2 disease and in age-matched controls8

Early-language-delay studies in children with CLN2 versus controls
Language delay and seizures may be common symptoms on their own, but the combination of early language delay prior to seizure presentation should raise the level of suspicion for CLN2 disease. It is important to ask carers about early language development, even if current abilities appear normal.7,8

Language delay and seizures may be common symptoms on their own, but the combination of early language delay prior to seizure presentation should raise the level of suspicion for CLN2 disease. It is important to ask carers about early language development, even if current abilities appear normal.1,7

Not all children will have early language delay – some children may exhibit ataxia or other developmental delays as early symptoms.9

When children aged 2–4 present with new-onset, unprovoked seizures…

  • PROBE on early language development, even if current abilities appear normal
  • FOCUS on key points of age-specific language acquisition before the onset of overt symptoms
  • TEST for CLN2 disease in children who have these two hallmark symptoms
Based on emerging data, probing on early language development preceding the onset of seizures can enable earlier diagnosis of CLN2 disease.
Dr Angela Schulz, MD, PhD
Children’s Hospital
NCL Specialty Clinic
International Center of Lysosomal Storage Disorders (ICLD)
University Medical Center Hamburg-­Eppendorf
Hamburg, Germany

A discussion about the early signs of CLN2 disease (new-­onset, unprovoked seizures and language delay) and how earlier diagnosis may benefit the child and their family.

References: 1. Fietz M et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016;119:160–167. 2. Schulz A et al. Biochim Biophys Acta 2013;1832:1801–1806. 3. Mole SE et al. Neurogenetics. 2005;6:107–126. 4. Pérez-Poyato MS et al. J Child Neurol 2013;28:470–478. 5. Chang M et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. The neuronal ceroid lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom:Oxford University Press; 2011:80–109. 6. Williams RE et al. Management Strategies for CLN2 Disease. Pediatr Neurol 2017;69:102–112. 7. Nickel M et al. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Lancet Child Adolesc Health 2018;2(8):582–590. 8. Nickel M et al. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Lancet Child Adolesc Health 2018;2(8):582–590. Supplementary Material. 9. Worgall S et al. Hum Gene Ther 2008;19:463–474.