- Impaired vibration sensation in the lower limbs (HP:0002166): A decrease in the ability to perceive vibration in the legs. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Delayed brainstem auditory evoked response conduction time (HP:0004466): An abnormal increase (delay) in the conduction time of the brainstem auditory-evoked response. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Orthostatic hypotension (HP:0001278): A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: 2/2. (PMID:35904593)
- Dysmetria (HP:0001310): A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Gait ataxia (HP:0002066): A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Deep cerebral white matter hyperintensities (HP:0030892): Areas of brighter than expected signal on magnetic resonance imaging emanating from locations distant from the ventricular system. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Tinnitus (HP:0000360): Tinnitus is an auditory perception that can be described as the experience of sound, in the ear or in the head, in the absence of external acoustic stimulation. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: 1/1. (PMID:35904593)
- 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: PCS. Frequency: 1/1. (PMID:35904593)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: PCS. Frequency: 2/2. (PMID:35904593)
- Hypometric saccades (HP:0000571): Saccadic undershoot, i.e., a saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Broad-based gait (HP:0002136): An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: 1/1. (PMID:35904593)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 0/1. (PMID:35904593)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: 1/1. (PMID:35904593)
- Dysdiadochokinesis (HP:0002075): A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Pneumonia (HP:0002090): Inflammation of any part of the lung parenchyma. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 0/1. (PMID:35904593)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: PCS. Frequency: 1/2. (PMID:35904593)
- Anticardiolipin IgG antibody positivity (HP:0020136): The presence of circulating IgG autoantibodies to cardiolipin. Evidence: PCS. Frequency: 0/1. (PMID:35904593)
- Cerebral infarct (HP:0025722): A necrotic lesion in the cerebrum resulting from a sudden insufficiency of arterial or venous blood supply due to emboli, thrombi or mechanical factors. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: PCS. Frequency: 0/1. (PMID:35904593)
- Syncope (HP:0001279): A transient loss of consciousness (i.e., characterized by a rapid onset, a short duration, and a spontaneous and complete recovery) due to cerebral hypoperfusion. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- Absent Achilles reflex (HP:0003438): Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed. Evidence: PCS. Frequency: 1/1. (PMID:35904593)
- 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: PCS. (PMID:35904593)
These phenotypes are associated with the disease brain small vessel disease 6 with leukoencephalopathy (OMIM:621394).