- 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:8967754)
- Gaze-evoked nystagmus (HP:0000640): Nystagmus made apparent by looking to the right or to the left. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- Vertigo (HP:0002321): An abnormal sensation of spinning while the body is actually stationary. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- 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: 2/2. (PMID:8967754)
- 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: 1/3. (PMID:27683074)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- 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: 1/3. (PMID:27683074)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/3. (PMID:27683074)
- Unsteady gait (HP:0002317). Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Headache (HP:0002315): Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Loss of voice (HP:0001686). Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- Myalgia (HP:0003326): Pain in muscle. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 1/3. (PMID:27683074)
- Diplopia (HP:0000651): Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Truncal ataxia (HP:0002078): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- 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: 1/3. (PMID:27683074)
- Cardiomegaly (HP:0001640): Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. Evidence: PCS. Frequency: 3/3. (PMID:27683074)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 1/3. (PMID:27683074)
- 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: PCS. Frequency: 1/2. (PMID:8967754)
- Limb ataxia (HP:0002070): A kind of ataxia that affects movements of the extremities. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 1/3. (PMID:27683074)
- Dysesthesia (HP:0012534): Painful sensations elicited by a nonpainful cutaneous stimulus such as a light touch or gentle stroking over affected areas of the body. Sometimes referred to as hyperpathia or hyperalgesia. Often perceived as an intense burning, dyesthesias may outlast the stimulus by several seconds. Evidence: PCS. Frequency: 1/2. (PMID:8967754)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: PCS. Frequency: 1/3. (PMID:27683074)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 4/4. (PMID:8967754;PMID:27683074)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Peripheral visual field loss (HP:0007994): Loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision. Evidence: PCS. Frequency: 2/2. (PMID:8967754)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: PCS. Frequency: 3/3. (PMID:27683074)
- 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:10976639)
- Increased hepatic glycogen content (HP:0006568): An increase in the amount of glycogen stored in hepatocytes compared to normal. Evidence: PCS. Frequency: 1/1. (PMID:27683074)
- 3-Methylglutaconic aciduria (HP:0003535): An increased amount of 3-methylglutaconic acid in the urine. Evidence: PCS. Frequency: 2/2. (PMID:27683074)
These phenotypes are associated with the disease neurodegeneration with ataxia and late-onset optic atrophy (OMIM:619259).