Phenotypes associated with the disease multiple mitochondrial dysfunctions syndrome 9b (OMIM:620887):
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. Frequency: 3/3. (PMID:33348459;PMID:29040572)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Increased body weight (HP:0004324): Abnormally increased body weight. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Elevated mitochondrial citrate synthase activity (HP:6000195): Activity of the enzyme mitochondrial citrate synthase (EC:2.3.3.1) in muscle tissue is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- 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: PCS. Frequency: 1/1. (PMID:29040572)
- Gait imbalance (HP:0002141). Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 8/20. (PMID:30250212;PMID:33348459;PMID:37107710)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 4/4. (PMID:33348459;PMID:37046037;PMID:29040572)
- Paralysis (HP:0003470): Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 8/15. (PMID:30250212;PMID:29040572;PMID:37481223;PMID:37107710)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 2/6. (PMID:30250212;PMID:37481223)
- Abnormal circulating acylcarnitine concentration (HP:0012071): Any deviation from the normal concentration in the blood circulation of an acylcarnitine, which is produced by reversible esterification of the 3-hydroxyl group of carnitine. Evidence: PCS. Frequency: 0/3. (PMID:33348459;PMID:29040572)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Attenuation of retinal blood vessels (HP:0007843): Narrowing of the retinal blood vessels, both arterioles and venules. Evidence: PCS. Frequency: 6/6. (PMID:37481223;PMID:37107710)
- Interictal EEG abnormality (HP:0025373): Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge. Evidence: PCS. Frequency: 4/9. (PMID:29040572)
- 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: 0/3. (PMID:37046037;PMID:29040572)
- Ultra-low vision (HP:0032123): Best corrected visual acuity worse than 1.90 logMAR (roughly 20/1590). Evidence: PCS. Frequency: 2/2. (PMID:37107710)
- Cough (HP:0012735): A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Perifoveal ring of hyperautofluorescence (HP:0030629). Evidence: PCS. Frequency: 2/2. (PMID:37481223)
- Recurrent hand flapping (HP:0100023): A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Abnormal retinal nerve fiber layer morphology (HP:0020119): A structural abnormality of the retinal nerve fiber layer. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Nuclear cataract (HP:0100018): A nuclear cataract is an opacity or clouding that develops in the lens nucleus. That is, a nuclear cataract is one that is located in the center of the lens. The nucleus tends to darken changing from clear to yellow and sometimes brown. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Compound motor action potential abnormality (HP:0033580): An abnormal finding in a compound motor action potential measurement in EMG. Nerve conduction studies involve the application of a depolarising square wave electrical pulses to the skin over a peripheral nerve producing: (1) a propagated nerve action potential (NAP) recorded at a distant point over the same nerve: and (2) a compound muscle action potential (CMAP) arising from the activation of muscle fibers in a target muscle supplied by the nerve. In both cases these may be recorded with surface or needle electrodes. The CMAP is a summated voltage response from the individual muscle fiber action potentials. The shortest latency of the CMAP is the time from stimulus artifact to onset of the response and is a biphasic response with an initial upward deflection followed by a smaller downward deflection. The CMAP amplitude is measured from baseline to negative peak (the neurophysiological convention is that negative voltage is demonstrated by an upward deflection) and measured in millivolts (mV). Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- 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: 3/6. (PMID:29040572;PMID:37481223)
- Speech apraxia (HP:0011098): A type of apraxia that is characterized by difficulty or inability to execute speech movements because of problems with coordination and motor problems, leading to incorrect articulation. An increase of errors with increasing word and phrase length may occur. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- 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:37481223)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- 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: PCS. Frequency: 19/23. (PMID:30250212;PMID:33348459;PMID:29040572;PMID:37107710)
- Sensory neuropathy (HP:0000763): Peripheral neuropathy affecting the sensory nerves. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Abdominal pain (HP:0002027): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- 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: PCS. Frequency: 2/2. (PMID:30250212;PMID:37107710)
- Retinal pigment epithelial mottling (HP:0007814): Mottling (spots or blotches of different shades) of the retinal pigment epithelium, i.e., localized or generalized fundus pigment granularity associated with processes at the level of the retinal pigment epithelium. Evidence: PCS. Frequency: 5/5. (PMID:37481223;PMID:37107710)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/2. (PMID:30250212)
- 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: 4/10. (PMID:33348459;PMID:29040572;PMID:37481223;PMID:37107710)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 6/6. (PMID:29040572)
- Ambiguous genitalia (HP:0000062): A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale: Prader 0: Normal female external genitalia. Prader 1: Female external genitalia with clitoromegaly. Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus. Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening. Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus. Prader 5: Normal male external genitalia. The diagnosis of ambiguous genitalia is made for Prader 1-4. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: PCS. Frequency: 0/1. (PMID:29040572)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 3/3. (PMID:33348459;PMID:29040572)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 2/2. (PMID:29040572;PMID:37481223)
- Abnormal corpus callosum morphology (HP:0001273): Abnormality of the corpus callosum. Evidence: PCS. Frequency: 6/6. (PMID:29040572)
- Fused labia majora (HP:0025486): The outer labia are sealed together. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 3/3. (PMID:29040572)
- Moderately reduced visual acuity (HP:0030515): Moderate reduction of the ability to see. On the 6m visual acuity scale, moderate reduction is defined as less than 6/18 but at least 6/60. On the 20ft visual acuity scale, moderate reduction is defined as less than 20/70 but at least 20/200. On the decimal visual acuity scale, moderate reduction is defined as less than 0.3 but at least 0.1. Evidence: PCS. Frequency: 2/2. (PMID:37107710)
- 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: PCS. Frequency: 2/2. (PMID:29040572)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: PCS. Frequency: 3/3. (PMID:30250212;PMID:29040572)
- 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: PCS. Frequency: 1/1. (PMID:33348459)
- Photophobia (HP:0000613): Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light. Evidence: PCS. Frequency: 1/4. (PMID:37481223)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Ketosis (HP:0001946): Presence of elevated levels of ketone bodies in the body. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- 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: 1/1. (PMID:33348459)
- Meningitis (HP:0001287): Inflammation of the meninges. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/3. (PMID:29040572)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 4/4. (PMID:30250212;PMID:29040572)
- Cutaneous photosensitivity (HP:0000992): An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 14/18. (PMID:30250212;PMID:33348459;PMID:29040572)
- Abnormal basal ganglia morphology (HP:0002134): Abnormality of the basal ganglia. Evidence: PCS. Frequency: 3/6. (PMID:33348459)
- Febrile seizure (within the age range of 3 months to 6 years) (HP:0002373): A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years. Evidence: PCS. Frequency: 1/1. (PMID:37107710)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Cystoid macular edema (HP:0011505): Cystoid thickening of the retina that takes place due to accumulation of extracellular fluid in the macula as a nonspecific response to blood-retinal barrier breakdown. Histological studies show that radially orientated cystoid spaces consisting of ophthalmoscopically clear fluid are often clinically detectable in the macula area. Evidence: PCS. Frequency: 3/5. (PMID:29040572;PMID:37481223)
- Elongated mitochondria (HP:0034692): Increase in length of mitochondria. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Hyperacusis (HP:0010780): Over-sensitivity to certain frequency ranges of sound. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- 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: 1/4. (PMID:33348459;PMID:29040572)
- Abnormality of somatosensory evoked potentials (HP:0007377): An abnormality of somatosensory evoked potentials (SSEP), i.e., of the electrical signals of sensation going from the body to the brain in response to a defined stimulus. Recording electrodes are placed over the scalp, spine, and peripheral nerves proximal to the stimulation site. Clinical studies generally use electrical stimulation of peripheral nerves to elicit potentials. SSEP testing determines whether peripheral sensory nerves are able to transmit sensory information like pain, temperature, and touch to the brain. Abnormal SSEPs can result from dysfunction at the level of the peripheral nerve, plexus, spinal root, spinal cord, brain stem, thalamocortical projections, or primary somatosensory cortex. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Decreased activity of mitochondrial complex IV (HP:0008347): A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 1/3. (PMID:29040572)
- 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: PCS. Frequency: 1/1. (PMID:29040572)
- Blurred vision (HP:0000622): Lack of sharpness of vision resulting in the inability to see fine detail. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- Constriction of peripheral visual field (HP:0001133): An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- 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:30250212)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 1/1. (PMID:37107710)
- 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: PCS. Frequency: 5/13. (PMID:30250212;PMID:33348459;PMID:29040572;PMID:37481223)
- 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: 10/11. (PMID:33348459;PMID:29040572)
- 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: 8/10. (PMID:33348459;PMID:29040572;PMID:37481223;PMID:37107710)
- Mildly reduced visual acuity (HP:0032037): Mild reduction of the ability to see. On the 6m visual acuity scale, mild reduction is defined as less than 6/12 but at least 6/18. On the 20ft visual acuity scale, mild reduction is defined as less than 20/40 but at least 20/70. On the decimal visual acuity scale, mild reduction is defined as less than 0.5 but at least 0.3. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- 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: PCS. Frequency: 3/3. (PMID:29040572;PMID:37481223)
- Ultra-low vision with retained light perception (HP:0032286): Ultra-low vision but with retained ability to perceive the difference between light and dark. Evidence: PCS. Frequency: 4/4. (PMID:37481223;PMID:37107710)
- Agitation (HP:0000713): A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- 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: 1/1. (PMID:37481223)
- Impaired distal tactile sensation (HP:0006937): A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 2/2. (PMID:30250212;PMID:33348459)
- 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:37046037)
- 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: 20/21. (PMID:30250212;PMID:33348459;PMID:29040572;PMID:37107710)
- 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: 9/9. (PMID:37481223;PMID:37107710)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- Optic nerve hypoplasia (HP:0000609): Underdevelopment of the optic nerve. Evidence: PCS. Frequency: 2/2. (PMID:30250212;PMID:33348459)
- Decreased compound muscle action potential amplitude (HP:0033383): Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Upper limb hyperreflexia (HP:0007350): Increased intensity of the a reflex in the arm. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Appendicular spasticity (HP:0034353): A type of spasticity that affects one or more limbs (arms or legs). Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Decreased distal sensory nerve action potential (HP:0007230): A reduction in the amplitude of sensory nerve action potential in distal nerve segments. This feature is measured by nerve conduction studies. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 1/3. (PMID:33348459)
- Abnormal mitochondrial morphology (HP:0008322): Any structural anomaly of the mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:29040572)
- Central scotoma (HP:0000603): An area of depressed vision located at the point of fixation and that interferes with central vision. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 5/12. (PMID:33348459;PMID:29040572)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. Frequency: 3/3. (PMID:30250212;PMID:29040572)
- Optic neuropathy (HP:0001138). Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- 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: 1/1. (PMID:33348459)
- Abnormal diffusion weighted cerebral MRI morphology (HP:0032615): A diffusion abnormality observed in diffusion-weighted magnetic resonance imaging (MRI) of the brain. Molecular diffusion refers to the notion that any type of molecule in a fluid (eg, water) is randomly displaced as the molecule is agitated by thermal energy. Restricted diffusion of water appears bright on diffusion-weighted images. Evidence: PCS. Frequency: 6/6. (PMID:29040572)
- Vertigo (HP:0002321): An abnormal sensation of spinning while the body is actually stationary. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- 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:30250212)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 2/3. (PMID:33348459;PMID:29040572)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Decreased activity of mitochondrial complex II (HP:0008314): A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/4. (PMID:29040572)
- Unsteady gait (HP:0002317). Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Ventilator dependence with inability to wean (HP:0005946). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Retinal atrophy (HP:0001105): A nonspecific term denoting wasting, especially as a result of degeneration, of the retinal pigment epithelium (RPE) and neurosensory retinal cells. Evidence: PCS. Frequency: 2/2. (PMID:37481223)
- Retinal thinning on OCT (HP:0030329): Reduced anteroposterior thickness of the retina. This phenotype can be appreciated by retinal optical coherence tomography (OCT). Evidence: PCS. Frequency: 2/2. (PMID:37107710)
- Motor regression (HP:0033044): Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones. Evidence: PCS. Frequency: 2/2. (PMID:33348459;PMID:29040572)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Drowsiness (HP:0002329): Abnormal feeling of sleepiness or difficulty staying awake. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Clitoral hypertrophy (HP:0008665): Hypertrophy of the clitoris. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Tetraplegia (HP:0002445): Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: PCS. Frequency: 4/4. (PMID:33348459;PMID:29040572;PMID:37107710)
- Hyperopic astigmatism (HP:0000484): A form of astigmatism in which one meridian is hyperopic while the one at a right angle to it has no refractive error. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- 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: PCS. Frequency: 4/4. (PMID:29040572;PMID:37107710)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 6/10. (PMID:33348459;PMID:37046037;PMID:29040572;PMID:37107710)
- 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: 2/2. (PMID:33348459;PMID:29040572)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 4/5. (PMID:33348459;PMID:29040572)
- Slow pupillary light response (HP:0030211): Reduced velocity and acceleration in the pupillary light response. Evidence: PCS. Frequency: 1/1. (PMID:37107710)
- Type I diabetes mellitus (HP:0100651): A chronic condition in which the pancreas produces little or no insulin. Type I diabetes mellitus is manifested by the sudden onset of severe hyperglycemia with rapid progression to diabetic ketoacidosis unless treated with insulin. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/4. (PMID:29040572)
- Increased mitochondrial number (HP:0040014). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 3/3. (PMID:29040572;PMID:37107710)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/12. (PMID:33348459;PMID:29040572)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Decreased activity of mitochondrial complex III (HP:0011924): A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/4. (PMID:29040572)
- Hypoventilation (HP:0002791): A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide). Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Decreased activity of mitochondrial complex I (HP:0011923): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/4. (PMID:29040572)
- Pes valgus (HP:0008081): An outward (valgus) deviation of the calcaneus relative to the longitudinal axis of the lower leg at the talocalcaneal (subtalar) joint, such that the heel is everted. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Distal lower limb muscle weakness (HP:0009053): Reduced strength of the distal musculature of the legs. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Urogenital sinus anomaly (HP:0100779): A rare birth defect in women where the urethra and vagina both open into a common channel. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Enuresis (HP:0000805): Lack of the ability to control the urinary bladder leading to involuntary urination at an age where control of the bladder should already be possible. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- 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:29040572)
- Papule (HP:0200034): A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- 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: 1/1. (PMID:29040572)
- Asthenia (HP:0025406): A state characterized by a feeling of weakness and loss of strength leading to a generalized weakness of the body. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: PCS. Frequency: 2/2. (PMID:29040572)
- Insomnia (HP:0100785): Persistent difficulty in starting or maintaining sleep, or waking up earlier than desired, despite having adequate opportunities and conditions for sleep. Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- Reduced visual acuity (HP:0007663). Evidence: PCS. Frequency: 1/1. (PMID:37481223)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Frequency: 3/3. (PMID:30250212;PMID:29040572)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 1/4. (PMID:37481223)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 4/16. (PMID:37046037;PMID:37481223;PMID:37107710)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/2. (PMID:33348459;PMID:29040572)
- 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: 4/4. (PMID:33348459;PMID:29040572;PMID:37107710)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 2/2. (PMID:33348459)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: PCS. Frequency: 3/3. (PMID:29040572)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Falls (HP:0002527). Evidence: PCS. Frequency: 2/2. (PMID:33348459;PMID:37046037)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Areflexia of lower limbs (HP:0002522): Inability to elicit tendon reflexes in the lower limbs. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Decreased mean corpuscular volume (HP:0025066): A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters). Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 2/7. (PMID:33348459;PMID:29040572)
- 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: 3/3. (PMID:30250212;PMID:29040572)
- Profound intellectual disability (HP:0002187): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Spastic gait (HP:0002064): Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Hyperesthesia (HP:0100963): Increased sensitivity to stimulation, excluding the special senses, which may refer to various modes of cutaneous sensibility including touch and thermal sensation without pain, as well as to pain. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 12/22. (PMID:33348459;PMID:37481223;PMID:37107710)
- Decreased activity of mitochondrial respiratory chain (HP:0008972): Decreased activity of the mitochondrial respiratory chain. Evidence: PCS. Frequency: 0/1. (PMID:33348459)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Retinal dystrophy (HP:0000556): Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: PCS. Frequency: 2/2. (PMID:29040572)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Wheezing (HP:0030828): A high-pitched whistling sound associated with labored breathing. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Hypercapnia (HP:0012416): Abnormally elevated blood carbon dioxide (CO2) level. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- 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:30250212)
- Dysesthesia (HP:0012534): Painful sensations elicited by a nonpainful cutaneous stimulus such as a light touch or gentle stroking over affected areas of the body. Sometimes referred to as hyperpathia or hyperalgesia. Often perceived as an intense burning, dyesthesias may outlast the stimulus by several seconds. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Diffuse cerebral atrophy (HP:0002506): Diffuse unlocalised atrophy affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- 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: 3/3. (PMID:33348459;PMID:37481223;PMID:37107710)
- Abnormal brain lactate level by MRS (HP:0025045): A deviation from normal of the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 0/1. (PMID:33348459)
- Nyctalopia (HP:0000662): Inability to see well at night or in poor light. Evidence: PCS. Frequency: 11/19. (PMID:29040572;PMID:37481223;PMID:37107710)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: PCS. Frequency: 2/2. (PMID:37107710)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: PCS. Frequency: 1/1. (PMID:33348459)
- Abnormal circulating creatine kinase activity (HP:0040081): Any deviation from the normal activity of creatine kinase in the blood circulation. Evidence: PCS. Frequency: 0/1. (PMID:29040572)
- Pain (HP:0012531): An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Evidence: PCS. Frequency: 2/3. (PMID:33348459;PMID:29040572)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/4. (PMID:30250212;PMID:33348459;PMID:29040572)
- Perimembranous ventricular septal defect (HP:0011682): A ventricular septal defect that is confluent with and involves the membranous septum and is bordered by an atrioventricular valve, not including the type 3 VSDs. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/1. (PMID:30250212)
- Undetectable electroretinogram (HP:0000550): Lack of any response to stimulation upon electroretinography. Evidence: PCS. Frequency: 3/3. (PMID:37481223)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 4/8. (PMID:33348459;PMID:29040572)
- Poor visual behavior for age (HP:0025152): Lack of visual responsiveness or decrease in visual capabilities suggesting a lack of visual responsiveness or decrease in visual capabilities in an infant or young child in which visual behavior fails to meet normal developmental milestones. Evidence: PCS. Frequency: 3/3. (PMID:37107710)
- Hyperautofluorescent retinal lesion (HP:0025158): Increased amount of autofluorescence in the retina as ascertained by fundus autofluorescence imaging. Evidence: PCS. Frequency: 2/2. (PMID:37107710)
- Lower limb pain (HP:0012514): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the leg. Evidence: PCS. Frequency: 1/1. (PMID:37046037)
- Extra-axial cerebrospinal fluid accumulation (HP:0012510): An increased amount of cerebrospinal fluid (CSF) in the subarachnoid space. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: PCS. Frequency: 1/2. (PMID:33348459;PMID:29040572)
- Retinal degeneration (HP:0000546): A nonspecific term denoting progressive loss of the retinal pigment epithelium (RPE) and/or neurosensory retinal cells. Evidence: PCS. Frequency: 1/1. (PMID:37107710)
- Tip-toe gait (HP:0030051): An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait. Evidence: PCS. Frequency: 1/1. (PMID:29040572)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 20/20. (PMID:33348459;PMID:29040572;PMID:37481223;PMID:37107710)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 2/2. (PMID:33348459;PMID:29040572)