Phenotypes associated with the disease Autosomal dominant progressive external ophthalmoplegia (ORPHA:254892):
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:254892)
- External ophthalmoplegia (HP:0000544): Paralysis of the external ocular muscles. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:254892)
- Hypomimic face (HP:0000338): A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Abnormality of eye movement (HP:0000496): An abnormality in voluntary or involuntary eye movements or their control. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Ophthalmoparesis (HP:0000597): Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Shoulder girdle muscle weakness (HP:0003547): The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Quadriceps muscle weakness (HP:0003731): Weakness of the quadriceps muscle (that is, of the muscle fasciculus of quadriceps femoris). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Mitochondrial myopathy (HP:0003737): A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Abnormality of the mitochondrion (HP:0012103): An anomaly of the mitochondrion, the membranous cytoplasmic organelle the interior of which is subdivided by cristae. The mitochondrion is a self replicating organelle that is the site of tissue respiration. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:254892)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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). (ORPHA:254892)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Facial diplegia (HP:0001349): Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Left ventricular hypertrophy (HP:0001712): Enlargement or increased size of the heart left ventricle. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Glucose intolerance (HP:0001952): Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Frequent falls (HP:0002359). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Hypokinesia (HP:0002375): Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Cogwheel rigidity (HP:0002396): A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Exertional dyspnea (HP:0002875): Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Myalgia (HP:0003326): Pain in muscle. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Difficulty climbing stairs (HP:0003551): Reduced ability to climb stairs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Ventricular arrhythmia (HP:0004308). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Atrial fibrillation (HP:0005110): An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Focal white matter lesions (HP:0007042). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- 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). (ORPHA:254892)
- Reduced left ventricular ejection fraction (HP:0012664): A diminution of the volumetric fraction of blood pumped out of the ventricle with each cardiac cycle. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:254892)
- Nocturia (HP:0000017): Abnormally increased production of urine during the night leading to an unusually frequent need to urinate. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Diabetes mellitus (HP:0000819): A group of abnormalities characterized by hyperglycemia and glucose intolerance. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Hyperthyroidism (HP:0000836): An abnormality of thyroid physiology characterized by excessive secretion of the thyroid hormones thyroxine (i.e., T4) and/or 3,3',5-triiodo-L-thyronine zwitterion (i.e., triiodothyronine or T3). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Goiter (HP:0000853): An enlargement of the thyroid gland. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- 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: Very rare (HP:0040284). (ORPHA:254892)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Abnormality of the liver (HP:0001392): An abnormality of the liver. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Ketosis (HP:0001946): Presence of elevated levels of ketone bodies in the body. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Palpitations (HP:0001962): A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Muscle spasm (HP:0003394): Sudden and involuntary contractions of one or more muscles. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Bipolar affective disorder (HP:0007302): Bipolar disorder is an illness of mood characterized by alternating episodes of elevated and depressed moods, which are interspersed with euthymic periods. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:254892)