Phenotypes associated with the disease sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (OMIM:607459):
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Sensory ataxic neuropathy (HP:0003434). Evidence: PCS. (PMID:12565911)
- 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: IEA. (OMIM:607459)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. (PMID:12565911)
- 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:12565911)
- Difficulty climbing stairs (HP:0003551): Reduced ability to climb stairs. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- 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: 4/7. (PMID:12565911)
- Fiber type grouping (HP:0033685): An abnormal distribution of muscle fiber types in muscle tissue. Human skeletal muscle contains at least two fiber types recognizable by histochemical techniques. In transverse sections of normal skeletal muscle, type 1 and type 2 fibers are distributed in a random fashion. Grouping of fibers of the same type can be seen in certain peripheral neuropathies, thought to be due to reinnervation of denervated muscle fibers by sprouting axons. With grouping, motor units enlarge. The fibers of a motor unit, which are normally scattered, come to lie adjacent to one another. Histochemical examination shows groups of muscle fibers of the same histochemical type. Evidence: PCS. Frequency: 1/3. (PMID:12565911)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Diminished ability to concentrate (HP:0031987): The inability to focus or concentrate on a specific task, activity, or object. The subject may find themselves unable to grasp or understand written text and re-reads frequently without understanding. Familiar tasks or activities are severely compromised due to the lack of ability to concentrate. Thinking through multi-step problems is typically very difficult or impossible, leading to avoidance of such activities. Evidence: IEA. (OMIM:607459)
- Progressive gait ataxia (HP:0007240): A type of gait ataxia displaying progression of clinical severity. Evidence: PCS. (PMID:12565911)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:607459)
- 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: 1/7. (PMID:12565911)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:607459)
- Emotional lability (HP:0000712): Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. (PMID:12565911)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 7/7. (PMID:12565911)
- Subsarcolemmal accumulations of abnormally shaped mitochondria (HP:0003548): An abnormally increased number of mitochondria in the cytoplasma adjacent to the sarcolemma (muscle cell membrane), whereby the mitochondria also possess an abnormal morphology. Evidence: IEA. (OMIM:607459)
- Ophthalmoparesis (HP:0000597): Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Gastroparesis (HP:0002578): Decreased strength of the muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction. Evidence: IEA. (OMIM:607459)
- Exercise intolerance (HP:0003546): A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: IEA. (OMIM:607459)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:607459)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: PCS. (PMID:12565911)
- Centrally nucleated skeletal muscle fibers (HP:0003687): An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells). Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Ragged-red muscle fibers (HP:0003200): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: PCS. Frequency: 2/2. (PMID:12565911)
- Impaired distal proprioception (HP:0006858): A loss or impairment of the sensation of the relative position of parts of the body and joint position occurring at distal joints. Evidence: PCS. (PMID:12565911)
- 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: 1/7. (PMID:12565911)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: IEA. (OMIM:607459)
- Impaired distal tactile sensation (HP:0006937): A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus. Evidence: PCS. (PMID:12565911)
- 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: 5/8. (PMID:12565911)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: TAS. (OMIM:607459)
- Sensory ataxia (HP:0010871): Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- 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: 1/7. (PMID:12565911)
- 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: 1/7. (PMID:12565911)
- 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:12565911)
- Muscle fiber necrosis (HP:0003713): Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers. Evidence: PCS. (PMID:12565911)
- Mitral regurgitation (HP:0001653): An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- 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: 1/7. (PMID:12565911)
- Hypernasal speech (HP:0001611): A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: IEA. (OMIM:607459)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. Frequency: 3/3. (PMID:12565911)
- Retinal pigment epithelial mottling (HP:0007814): Mottling (spots or blotches of different shades) of the retinal pigment epithelium, i.e., localized or generalized fundus pigment granularity associated with processes at the level of the retinal pigment epithelium. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Hypoesthesia (HP:0033748): Decreased ability to perceive touch. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Abnormal vestibular function (HP:0001751): An abnormality of the functioning of the vestibular apparatus. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Intestinal pseudo-obstruction (HP:0004389): A functional rather than mechanical obstruction of the intestines, associated with manifestations that resemble those caused by an intestinal obstruction, including distension, abdominal pain, nausea, vomiting, constipation or diarrhea, in an individual in whom a mechanical blockage has been excluded. Evidence: IEA. (OMIM:607459)
- 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: 1/7. (PMID:12565911)
- Scapular winging (HP:0003691): Abnormal protrusion of the scapula away from the surface of the back. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Weakness of facial musculature (HP:0030319): Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve). Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Muscle fibrillation (HP:0010546): Fine, rapid twitching of individual muscle fibers with little or no movement of the muscle as a whole as ascertained by electromyography (EMG). If a motor neuron or its axon is destroyed, the muscle fibers it innervates undergo denervation atrophy. This leads to hypersensitivity of individual muscle fibers to acetyl choline so that they may contract spontaneously. Isolated activity of individual muscle fibers is generally so fine it cannot be seen through the intact skin, although it can be recorded as a short-duration spike in the EMG. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: IEA. (OMIM:607459)
- Atrophy/Degeneration involving the spinal cord (HP:0007344). Evidence: IEA. (OMIM:607459)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 3/7. (PMID:12565911)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 2/2. (PMID:12565911)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/7. (PMID:12565911)
- 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. (PMID:12565911)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 1/1. (PMID:12565911)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: PCS. Frequency: 6/7. (PMID:12565911)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 5/7. (PMID:12565911)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Mildly elevated creatine kinase (HP:0008180). Evidence: PCS. Frequency: 1/7. (PMID:12565911)
- Early young adult onset (HP:0025708): Onset of disease at an age of greater than or equal to 16 to under 19 years. Evidence: PCS. Frequency: 1/1. (PMID:12565911)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. Frequency: 6/7. (PMID:12565911)
- Positive Romberg sign (HP:0002403): The patient stands with the feet placed together and balance and is asked to close his or her eyes. A loss of balance upon eye closure is a positive Romberg sign and is interpreted as indicating a deficit in proprioception. Evidence: PCS. Frequency: 2/7. (PMID:12565911)
- Impaired distal vibration sensation (HP:0006886): A decrease in the ability to perceive vibration in the distal portions of the limbs. Evidence: PCS. (PMID:12565911)
- Mitral valve prolapse (HP:0001634): One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle. Evidence: PCS. Frequency: 3/7. (PMID:12565911)
- External ophthalmoplegia (HP:0000544): Paralysis of the external ocular muscles. Evidence: PCS. Frequency: 6/7. (PMID:12565911)