- 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: IEA. (OMIM:617710)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: IEA. (OMIM:617710)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 2/2. (PMID:28236339)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: IEA. (OMIM:617710)
- 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: IEA. (OMIM:617710)
- 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: 1/1. (PMID:28650581)
- 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: IEA. Frequency: Very rare (HP:0040284). (OMIM:617710)
- 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: IEA. (OMIM:617710)
- 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: PCS. Frequency: 2/2. (PMID:28236339)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Severe temper tantrums (HP:0025162): Temper tantrums, which occur with more severe symptomatology compared to a temper tantrum that occurs as a part of normal developmental process. Evidence: PCS. Frequency: 2/2. (PMID:28236339)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 2/2. (PMID:28236339)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Rod-cone dystrophy (HP:0000510): An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones. Evidence: IEA. Frequency: Very rare (HP:0040284). (OMIM:617710)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 2/2. (PMID:28236339)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 3/3. (PMID:28236339;PMID:28650581)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: IEA. (OMIM:617710)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: IEA. (OMIM:617710)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 11/11. (OMIM:617710;PMID:28650581)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:617710)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: IEA. (OMIM:617710)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- 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: 2/2. (PMID:28236339)
- 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:617710)
- 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: PCS. Frequency: 3/3. (PMID:28236339;PMID:28650581)
- Multifocal seizures (HP:0031165): Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations). Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Limb hypertonia (HP:0002509). Evidence: IEA. (OMIM:617710)
- Diffuse cerebral atrophy (HP:0002506): Diffuse unlocalised atrophy affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Amblyopia (HP:0000646): Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- 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:28236339)
- 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: IEA. (OMIM:617710)
- 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: IEA. Frequency: Very rare (HP:0040284). (OMIM:617710)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: IEA. (OMIM:617710)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: PCS. Frequency: 2/2. (PMID:28236339)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/1. (PMID:28650581)
These phenotypes are associated with the disease neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (OMIM:617710).