As mentioned, NCL8 (depending on CLN8mutation) can manifest in four described to date (subtypes) clinical presentations - vLINCL, EPMR, congenital NCL8, and atypical late infantile NCL. Below you can find short characteristics of each subtype.
Congenital NCL8 (cNCL8)
The case of cNCL8 was described in an Argentinian child born with severe muscle flabbiness. Since birth, there were signs of the child’s development delay (language was never developed). At the age of 3, seizures (generalized tonic-clonic) started. After three years, involuntary muscle twitching and problems with muscle movement coordination arose, with an MRI study showing cerebellar degeneration. At 12, the child died.
Late infantile NCL variant (vLINCL)
Patients with vLINCL subtype manifest signs of disease around the fifth year of age. Moreover, from the beginning, it progresses rapidly, so patients are losing their movement ability in two to four years.
Seizures
Most patients present generalized tonic-clonic seizures with disease onset. Additionally, involuntary muscle twitching (myoclonus) often occurs.
Cognitive decline
As the disease progresses rapidly it usually severely affects cognitive functions. Patients mostly display delay of speech.
Cerebellar atrophy
Cerebellar degeneration is detected with MRI studies in all symptomatic patients. Clinical symptoms include problems with muscle movement coordination (ataxia), gait imbalance, and (speech articulation problems) dysarthria.
Visual disturbance
All patients have retinal pathology leading to visual loss. The vision acuity starts to deteriorate rapidly with disease onset (typically near the fifth year of age). The outcome is usually severe. Studies reported that retinal degeneration could be detected in the peripheral retina and macular area. Moreover, often optic nerve atrophy is also present.
Atypical late infantile NCL (aLINCL)
Some of the described patients do not present the classic vLINCL or EMPR signs. Due to the presence of retinal pathologies, most likely they should be treated as atypical vLINCL manifestations.
The symptoms arise at the range of 5-16 years of age and are progressing slower than in vLINCL patients. Usually, epilepsy is the first sign of disease. Seizures can be generalized, but also partial seizures are observed. Involuntary muscle twitching (myoclonus) is typically absent. Development in infancy may be delayed, and the cognitive outcome is better than in vLINCL patients. In some cases, cerebellar degeneration and accompanying clinical signs (problems with muscle movement coordination, abnormal gait, and speech impairment) can develop.
Progressive epilepsy with mental retardation (EPMR)
EPMR manifests a little later than vLINCL, at the age of 7-9, with a normal development period up until epilepsy occurs. The disease progression rate is slower, and young adults often are still able to walk. The patients may reach 50 or 60 years of age.
Seizures
EPMR usually presents with generalized tonic-clonic seizures around the age of 5-10. The seizures occur once every one or two months in the beginning. Then their frequency rises, having its peak in puberty. In adulthood, epilepsy is often less severe, however still present. The seizures in one-third of cases may also manifest as complex focal seizures. Involuntary muscle twitching (myoclonus) is uncommon.
Cognitive decline
Unfortunately, within a few years from seizures onset, cognitive deterioration begins. Even with clinical suppression of seizures, the treatment is not disease-modifying, so cognitive decline continues. As a result, most patients are moderately/profoundly intellectually disabled in adulthood.
Cerebellar atrophy
Neurological symptoms develop with the disease progression, such as cerebellar degeneration. Thus, cerebellar ataxia (problems with muscle movement coordination) and dysarthric speech (speech articulation problems) are arising.
Visual disturbance
Usually, patients do not present evident ocular pathology, but in some visual acuity decrease (without distinct retinal pathology) may occur. Probably mild optical nerve atrophy develops.
CLN8