- 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: PCS. Frequency: 1/1. (PMID:40499538)
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- 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:40499538)
- Elevated brain lactate level by MRS (HP:0012707): An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 0/1. (PMID:40499538)
- 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: PCS. Frequency: 1/1. (PMID:40499538)
- Broad face (HP:0000283): Bizygomatic (upper face) and bigonial (lower face) width greater than 2 standard deviations above the mean (objective); or an apparent increase in the width of the face (subjective). Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Muscle fiber atrophy (HP:0100295). Evidence: PCS. Frequency: 1/2. (PMID:40499538)
- Increased endomysial connective tissue (HP:0100297): An increased volume of the endomysium, which is a connective tissue sheath that surrounds each muscle fiber. Together, bundles of muscle fibers form a fasciculus, surrounded by another layer of connective tissue called the perimysium. Evidence: PCS. Frequency: 1/2. (PMID:40499538)
- Impaired executive functioning (HP:0033051): A disturbance of executive functioning, which is broadly defined as the set of abilities that allow for the planning, executing, monitoring, and self-correcting of goal-directed behavior while inhibiting task-irrelevant behavior. At least some degree of executive skill is needed to complete most cognitive tasks, and deficits in executive abilities are central to many clinical conditions, including fronto-temporal dementia. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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:40499538)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Abnormal subthalamic nucleus morphology (HP:0025737): Any structural anomaly of the subthalamic nucleus, a small lens-shaped structure located within the diencephalon near the junction with the midbrain. The subthalamic nucleus composes the majority of the subthalamus along with the subthalamic fasciculus, ansa lenticularis, and several other smaller structures. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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: PCS. Frequency: 1/1. (PMID:40499538)
- 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: 2/2. (PMID:40499538)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- 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: PCS. Frequency: 1/1. (PMID:40499538)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Polyphagia (HP:0002591): A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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: 1/1. (PMID:40499538)
- 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: 2/2. (PMID:40499538)
- Ventricular septal hypertrophy (HP:0005144): The dividing wall between left and right sides of the heart, thickens and bulges into the left ventricle. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Severely reduced visual acuity (HP:0001141): Severe reduction of the ability to see. On the 6m visual acuity scale, severe reduction is defined as less than 6/60 but at least 3/60. On the 20ft visual acuity scale, severe reduction is defined as less than 20/200 but at least 20/400. On the decimal visual acuity scale, severe reduction is defined as less than 0.1 but at least 0.05. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 2/3. (PMID:40499538)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Progressive visual loss (HP:0000529): A reduction of previously attained ability to see. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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:40499538)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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:40499538)
- Retinopathy (HP:0000488): Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality. Evidence: PCS. Frequency: 0/1. (PMID:40499538)
- Respiratory failure requiring assisted ventilation (HP:0004887): A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Gaze-evoked horizontal nystagmus (HP:0007979): Horizontal nystagmus made apparent by looking to the right or to the left. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Vertical nystagmus (HP:0010544): Vertical nystagmus may present with either up-beating or down-beating eye movements or both. When present in the straight-ahead position of gaze it is referred to as upbeat nystagmus or downbeat nystagmus. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/2. (PMID:40499538)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 1/2. (PMID:40499538)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 1/2. (PMID:40499538)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 2/2. (PMID:40499538)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/2. (PMID:40499538)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 1/1. (PMID:40499538)
- 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: 1/1. (PMID:40499538)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/3. (PMID:40499538)
These phenotypes are associated with the disease mitochondrial complex IV deficiency, nuclear type 24 (OMIM:621431).