- Sensory ataxic neuropathy (HP:0003434). Evidence: IEA. (OMIM:258450)
- 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: 0/1. (PMID:32042919)
- 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: 2/2. (PMID:34777884;PMID:32042919)
- 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. (OMIM:258450)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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:30838265)
- Difficulty climbing stairs (HP:0003551): Reduced ability to climb stairs. Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- 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:258450)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- Muscle fiber atrophy (HP:0100295). Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: IEA. (OMIM:258450)
- 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:258450)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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: IEA. (OMIM:258450)
- Dyschromatopsia (HP:0007641): A form of colorblindness in which only two of the three fundamental colors can be distinguished due to a lack of one of the retinal cone pigments. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:258450)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- 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:258450)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 2/2. (PMID:34777884;PMID:32042919)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: IEA. (OMIM:258450)
- 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:258450)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 0/1. (PMID:30838265)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:258450)
- Truncal ataxia (HP:0002078): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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:34777884;PMID:32042919)
- 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. (OMIM:258450)
- 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: IEA. (OMIM:258450)
- 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: 1/1. (PMID:30838265)
- 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: 1/1. (PMID:30838265)
- 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: 1/1. (PMID:30838265)
- Limb ataxia (HP:0002070): A kind of ataxia that affects movements of the extremities. Evidence: IEA. (OMIM:258450)
- 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: IEA. (OMIM:258450)
- 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: 1/1. (PMID:32042919)
- 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:11431686)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:258450)
- Respiratory insufficiency due to muscle weakness (HP:0002747). Evidence: TAS. (OMIM:258450)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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:258450)
- 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: IEA. (OMIM:258450)
- 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: 2/2. (PMID:34777884;PMID:32042919)
- 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: PCS. Frequency: 1/1. (PMID:30838265)
- Steppage gait (HP:0003376): An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again. Evidence: IEA. (OMIM:258450)
- 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: 1/1. (PMID:30838265)
- 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: 1/1. (PMID:34777884)
- Intention tremor (HP:0002080): A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 1/1. (PMID:32042919)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 1/1. (PMID:34777884)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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: 0/1. (PMID:30838265)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 3/3. (PMID:34777884;PMID:30838265;PMID:32042919)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:258450)
- Mildly elevated creatine kinase (HP:0008180). Evidence: TAS. (OMIM:258450)
- Secondary amenorrhea (HP:0000869). Evidence: PCS. Frequency: 1/1. (PMID:30838265)
- 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:258450)
- 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). (OMIM:258450)
- Increased CSF protein concentration (HP:0002922): Increased concentration of protein in the cerebrospinal fluid. Evidence: IEA. (OMIM:258450)
- 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:258450)
- 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: PCS. (PMID:30838265)
- 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: IEA. (OMIM:258450)
- Impaired distal vibration sensation (HP:0006886): A decrease in the ability to perceive vibration in the distal portions of the limbs. Evidence: IEA. (OMIM:258450)
- 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: IEA. (OMIM:258450)
- 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:258450)
These phenotypes are associated with the disease progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 (OMIM:258450).