GTR Home > Conditions/Phenotypes > Juvenile neuronal ceroid lipofuscinosis

Disease characteristics

Excerpted from the GeneReview: Neuronal Ceroid-Lipofuscinoses
The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by mutations in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available.

Associated genes

Clinical features

Help
  • Psychomotor deterioration
  • Progressive inability to walk
  • Fingerprint intracellular accumulation of autofluorescent lipopigment storage material
  • Vacuolated lymphocytes
  • Dysarthria
  • Intellectual disability
  • Macular degeneration
  • Abolished electroretinogram (ERG)
  • Increased extraneuronal autofluorescent lipopigment
  • Progressive visual loss
  • Seizure
  • Anxiety
  • Retinitis pigmentosa
  • Blindness
  • Optic atrophy
  • Psychosis
  • Dementia
  • Parkinsonism
  • Abnormality of the cerebellum
  • Myoclonus
  • Cerebral atrophy
  • Increased neuronal autofluorescent lipopigment
  • Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
Show all (23)

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Write to the Help Desk