Phenotypes associated with the disease progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 (OMIM:157640):
- Resting tremor (HP:0002322): A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse. Evidence: IEA. (OMIM:157640)
- Facial palsy (HP:0010628): Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. Evidence: IEA. (OMIM:157640)
- 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: IEA. (OMIM:157640)
- 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:157640)
- 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: IEA. Frequency: 2/2. (OMIM:157640)
- 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: 1/2. (PMID:15534189)
- 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: IEA. (OMIM:157640)
- 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: IEA. (OMIM:157640)
- Slurred speech (HP:0001350): Abnormal coordination of muscles involved in speech. Evidence: PCS. Frequency: 1/2. (PMID:15534189)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: IEA. (OMIM:157640)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: IEA. Frequency: 1/2. (OMIM:157640)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: IEA. (OMIM:157640)
- 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:157640)
- Hypergonadotropic hypogonadism (HP:0000815): Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay. Evidence: IEA. (OMIM:157640)
- 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: 1/2. (PMID:15534189)
- 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:157640)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: IEA. (OMIM:157640)
- 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. Frequency: 2/2. (OMIM:157640)
- 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:157640)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: IEA. (OMIM:157640)
- Neck flexor weakness (HP:0003722): Weakness of the muscles involved in neck flexion (sternocleidomastoid, longus capitus, longus colli, and scalenus anterior). Evidence: PCS. Frequency: 1/2. (PMID:15534189)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:157640)
- Progressive muscle weakness (HP:0003323). Evidence: IEA. (OMIM:157640)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: IEA. (OMIM:157640)
- Total ophthalmoplegia (HP:0007824): Paralysis of both the extrinsic and intrinsic ocular muscles. Evidence: PCS. Frequency: 1/2. (PMID:15534189)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: IEA. (OMIM:157640)
- Hand tremor (HP:0002378): An unintentional, oscillating to-and-fro muscle movement affecting the hand. Evidence: PCS. Frequency: 1/2. (PMID:15534189)
- 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: 1/2. (PMID:15534189)
- 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: TAS. (OMIM:157640)
- 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: IEA. Frequency: 2/2. (OMIM:157640)
- 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:157640)
- 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: IEA. (OMIM:157640)
- Rhabdomyolysis (HP:0003201): Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream. Evidence: IEA. (OMIM:157640)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: IEA. (OMIM:157640)
- 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: IEA. (OMIM:157640)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: IEA. (OMIM:157640)
- 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:157640)
- Secondary amenorrhea (HP:0000869). Evidence: IEA. (OMIM:157640)
- 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: IEA. (OMIM:157640)
- 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. Frequency: 1/2. (OMIM:157640)
- Testicular atrophy (HP:0000029): Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility. Evidence: IEA. (OMIM:157640)
- Parkinsonism with favorable response to dopaminergic medication (HP:0002548): Parkinsonism is a clinical syndrome that is a feature of a number of different diseases, including Parkinson disease itself, other neurodegenerative diseases such as progressive supranuclear palsy, and as a side-effect of some neuroleptic medications. Some but not all individuals with Parkinsonism show responsiveness to dopaminergic medication defined as a substantial reduction of amelioration of the component signs of Parkinsonism (including mainly tremor, bradykinesia, rigidity, and postural instability) upon administration of dopaminergic medication. Evidence: IEA. (OMIM:157640)
- Impaired distal vibration sensation (HP:0006886): A decrease in the ability to perceive vibration in the distal portions of the limbs. Evidence: TAS. Frequency: 1/2. (OMIM:157640)
- 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: IEA. (OMIM:157640)
- 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:157640)
- 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:157640)
- 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: IEA. (OMIM:157640)
- Primary amenorrhea (HP:0000786). Evidence: IEA. (OMIM:157640)