- Mutism (HP:0002300): Complete lack of speech or verbal communication in a person despite attempts to engage in conversation. Mutism as a phenomena assumes the individual has previous capacity for speech and in the pediatric population it assumes that the person is past the age of typical language development. Evidence: TAS. (OMIM:221820)
- Bradykinesia (HP:0002067): Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement). Evidence: TAS. (OMIM:221820)
- 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: 1/3. (PMID:27423618)
- Apraxia (HP:0002186): A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements. Evidence: TAS. (OMIM:221820)
- Shuffling gait (HP:0002362): A type of gait (walking) characterized by by dragging one's feet along or without lifting the feet fully from the ground. Evidence: TAS. (OMIM:221820)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Somatic sensory dysfunction (HP:0003474): An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing. Evidence: PCS. Frequency: 1/3. (PMID:27423618)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: TAS. (OMIM:221820)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Impaired executive functioning (HP:0033051): A disturbance of executive functioning, which is broadly defined as the set of abilities that allow for the planning, executing, monitoring, and self-correcting of goal-directed behavior while inhibiting task-irrelevant behavior. At least some degree of executive skill is needed to complete most cognitive tasks, and deficits in executive abilities are central to many clinical conditions, including fronto-temporal dementia. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Central nervous system axonal spheroid (HP:0034381): Axonal spheroids are bubble-like biological features that form on most degenerating axons. During neurodegeneration, bubble-like swellings form along the length of the axon, a primary and early effect of dynamic axonal deformation. These varicosities, spheroids, or swellings have been described as beads on a string and branches bearing fruit, and they frequently appear on degenerating axons. The focal swellings on degenerating axons, axonal spheroids, are often filled with cellular debris such as organelles, pathological proteins, and disorganized cytoskeletal elements. Evidence: PCS. (PMID:27423618)
- 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: TAS. (OMIM:221820)
- Late young adult onset (HP:0025710): Onset of disease at an age of greater than or equal to 25 to under 40 years. Evidence: PCS. Frequency: 2/3. (PMID:27423618)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. (OMIM:221820)
- CNS demyelination (HP:0007305): A loss of myelin from nerve fibers in the central nervous system. Evidence: TAS. (OMIM:221820)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. (OMIM:221820)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Parkinsonism (HP:0001300): Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Memory impairment (HP:0002354): An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- 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:221820)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: TAS. (OMIM:221820)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: TAS. (OMIM:221820)
- Postural instability (HP:0002172): A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps. Evidence: TAS. (OMIM:221820)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. (OMIM:221820)
- Corpus callosum atrophy (HP:0007371): The presence of atrophy (wasting) of the corpus callosum. Evidence: PCS. Frequency: 3/3. (PMID:27423618)
- Frontal lobe dementia (HP:0000727). Evidence: TAS. (OMIM:221820)
- Neuronal loss in central nervous system (HP:0002529). Evidence: TAS. (OMIM:221820)
- Auditory hallucination (HP:0008765): Perception of sounds without auditory stimulus. Evidence: PCS. Frequency: 1/3. (PMID:27423618)
- Delusion (HP:0000746): A delusion is a fixed false belief held despite evidence to the contrary. The term delusion broadly encompasses all false judgments that possess the following external characteristics to a significant, albeit unspecified, extent: (1) they are held with an exceptional level of conviction, accompanied by an unparalleled subjective certainty; (2) there is an inability to consider alternative experiences or compelling counter-arguments; (3) the content of the belief is impossible. Evidence: PCS. Frequency: 1/3. (PMID:27423618)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. (OMIM:221820)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: TAS. (OMIM:221820)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: TAS. (OMIM:221820)
- Rapidly progressive (HP:0003678): Applies to a disease manifestation that quickly increases in scope or severity over the course of time. Evidence: TAS. (OMIM:221820)
These phenotypes are associated with the disease leukoencephalopathy, diffuse hereditary, with spheroids 1 (OMIM:221820).