Phenotypes associated with the disease ceroid lipofuscinosis, neuronal, 6B (Kufs type) (OMIM:204300):
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 8/14. (PMID:21549341)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:204300)
- Visual hallucination (HP:0002367): Visual perception in the absence of a visual stimulus. Evidence: TAS. (OMIM:204300)
- Middle age onset (HP:0003596): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 3/14. (PMID:21549341)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: IEA. (OMIM:204300)
- Late onset (HP:0003584): A type of adult onset with onset of symptoms after the age of 60 years. Evidence: PCS. Frequency: 1/14. (PMID:21549341)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: IEA. (OMIM:204300)
- Increased neuronal autofluorescent lipopigment (HP:0002074): Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the neuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient. Evidence: IEA. (OMIM:204300)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 7/11. (PMID:21549341)
- Status epilepticus without prominent motor symptoms (HP:0031475): There is inconclusive evidence to precisely define the duration of the seizure; however, based on current evidence an operational threshold of 10 minutes is appropriate as beyond this a seizure is likely to be more prolonged. The individual may or may not be aware or in coma. Evidence: PCS. Frequency: 1/14. (PMID:21549341)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: IEA. (OMIM:204300)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: IEA. (OMIM:204300)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: PCS. Frequency: 9/14. (PMID:21549341)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 10/14. (PMID:21549341)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:21549341)
- Auditory hallucination (HP:0008765): Perception of sounds without auditory stimulus. Evidence: TAS. (OMIM:204300)
- Fingerprint intracellular accumulation of autofluorescent lipopigment storage material (HP:0003208): An intracellular accumulation of autofluorescent lipopigment storage material in a trabecular or fingerprint-like pattern. Evidence: IEA. (OMIM:204300)
- Vascular granular osmiophilic material deposition (HP:0003657): Accumulation of granular osmiophilic material in blood vessel walls. Osmiophilic material becomes black upon staining with osmium tetroxide. Deposition of granular osmiophilic material (GOM) is the vascular pathological hallmark of CADASIL, which is the most prevalent hereditary small vessel disease and is caused by missense mutations in the NOTCH3 gene. GOM have been shown to contain NOTCH3 ectodomain (NOTCH3ECD) and extracellular matrix proteins, and can be visualized ultrastructurally in the tunica media of small arteries and capillaries. These electron dense GOM deposits are located in the basement membrane of mural cells, i.e. vascular smooth muscle cells and pericytes. In both manifest and pre-manifest CADASIL patients, GOM deposits are present not only in brain vessels, but also in vessels of other organs, such as the skin. Evidence: IEA. (OMIM:204300)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 2/14. (PMID:21549341)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: PCS. Frequency: 14/14. (PMID:21549341)
- Rectilinear intracellular accumulation of autofluorescent lipopigment storage material (HP:0003226): An intracellular accumulation of autofluorescent lipopigment storage material in a straight or rectilinear pattern. Evidence: IEA. (OMIM:204300)
- Curvilinear intracellular accumulation of autofluorescent lipopigment storage material (HP:0003205): An intracellular accumulation of autofluorescent lipopigment storage material in a curved pattern. Evidence: IEA. (OMIM:204300)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 8/14. (PMID:21549341)