Phenotypes associated with the disease progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 (OMIM:609286):
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: IEA. (OMIM:609286)
- Premature ovarian insufficiency (HP:0008209): Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian insuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: IEA. (OMIM:609286)
- Arrhythmia (HP:0011675): Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Diabetes mellitus (HP:0000819): A group of abnormalities characterized by hyperglycemia and glucose intolerance. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- 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:609286)
- 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:609286)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: TAS. (OMIM:609286)
- 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:609286)
- Hypogonadism (HP:0000135): A decreased functionality of the gonad. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: IEA. (OMIM:609286)
- 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: IEA. (OMIM:609286)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: IEA. (OMIM:609286)
- Myalgia (HP:0003326): Pain in muscle. Evidence: TAS. (OMIM:609286)
- Progressive muscle weakness (HP:0003323). Evidence: IEA. (OMIM:609286)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. (OMIM:609286)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. (OMIM:609286)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Onset: Late onset (HP:0003584). (OMIM:609286)
- 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: TAS. Frequency: Very rare (HP:0040284). (OMIM:609286)
- 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: IEA. (OMIM:609286)
- Bradycardia (HP:0001662): A slower than normal heart rate (in adults, slower than 60 beats per minute). Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Onset: Late onset (HP:0003584). (OMIM:609286)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: TAS. Frequency: 20/20. (OMIM:609286)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: IEA. Frequency: 20/20. (OMIM:609286)
- 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: IEA. (OMIM:609286)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: TAS. (OMIM:609286)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. (OMIM:609286)
- 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: TAS. (OMIM:609286)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: TAS. (OMIM:609286)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: TAS. Onset: Late onset (HP:0003584). (OMIM:609286)
- 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: TAS. Onset: Late onset (HP:0003584). (OMIM:609286)
- 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: IEA. (OMIM:609286)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- Progressive hearing impairment (HP:0001730): A progressive form of hearing impairment. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- 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: IEA. (OMIM:609286)
- Abnormality of the thyroid gland (HP:0000820): An abnormality of the thyroid gland. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:609286)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: IEA. (OMIM:609286)