Phenotypes associated with the disease progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 (OMIM:616479):
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- 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: PCS. (PMID:26094573)
- 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: 2/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)
- 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: 2/4. (PMID:26094573)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Muscle spasm (HP:0003394): Sudden and involuntary contractions of one or more muscles. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- 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: IEA. (OMIM:616479)
- Complete right bundle branch block (HP:0011712): A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Demyelinating motor neuropathy (HP:0007220): Demyelination of peripheral motor nerves. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Atrophy/Degeneration affecting the brainstem (HP:0007366). Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Reduced visual acuity (HP:0007663). Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Unsteady gait (HP:0002317). Evidence: PCS. Frequency: 4/4. (PMID:26094573)
- Axial muscle weakness (HP:0003327): Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs). Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 4/4. (PMID:26094573)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Ophthalmoparesis (HP:0000597): Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 3/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616479)
- Myalgia (HP:0003326): Pain in muscle. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: TAS. (OMIM:616479)
- 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. Frequency: 1/4. (PMID:26094573)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 4/4. (PMID:26094573)
- 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: 3/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 2/8. (PMID:26094573)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 4/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)
- 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: PCS. Frequency: 2/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616479)
- Intermediate young adult onset (HP:0025709): Onset of disease at an age of greater than or equal to 19 to under 25 years. Evidence: PCS. Frequency: 2/4. (PMID:26094573)
- 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: PCS. Frequency: 2/4. (PMID:26094573)
- 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: 2/4. (PMID:26094573)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- 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: PCS. Frequency: 1/4. (PMID:26094573)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: TAS. (OMIM:616479)
- 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:26094573)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/4. (PMID:26094573)
- 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: 1/4. (PMID:26094573)