- 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: 7/7. (PMID:17187620;PMID:15499950)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: PCS. Frequency: 2/2. (PMID:31844624;PMID:35112411)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 1/1. (PMID:34746378)
- 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: 1/1. (PMID:34746378)
- 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:23838601;PMID:29351582;PMID:31844624)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 16/22. (PMID:10805329;PMID:23838601;PMID:10545952;PMID:29351582;PMID:17187620;PMID:10749987;PMID:15499950;PMID:23364397)
- Abnormal brainstem MRI signal intensity (HP:0012747): A deviation from normal signal on magnetic resonance imaging (MRI) of the brainstem. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 4/6. (PMID:10805329;PMID:10545952)
- Irregular respiration (HP:0012195): Uneven rhythm of breathing. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Neuronal loss in basal ganglia (HP:0200147): A reduction in the number of nerve cells in the basal ganglia. Evidence: IEA. (OMIM:604377)
- Vocal cord paralysis (HP:0001605): A loss of the ability to move the vocal folds. Evidence: PCS. Frequency: 1/1. (PMID:18924171)
- Diffuse white matter abnormalities (HP:0007204). Evidence: PCS. Frequency: 1/1. (PMID:35112411)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 3/3. (PMID:16765077;PMID:18924171;PMID:23364397)
- Mixed demyelinating and axonal polyneuropathy (HP:0007327). Evidence: PCS. Frequency: 1/1. (PMID:29351582)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 3/4. (PMID:23407777;PMID:10545952)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/7. (PMID:23838601;PMID:15499950)
- Myofiber disarray (HP:0031318): A nonparallel arrangement of cardiac myocytes. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- 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: 9/10. (PMID:16765077;PMID:20159436;PMID:19353847;PMID:10545952;PMID:14994243;PMID:31844624;PMID:10749987;PMID:35112411)
- 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:10545952)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: PCS. Frequency: 1/1. (PMID:17187620)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 1/1. (PMID:19353847)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 4/4. (PMID:31844624;PMID:35112411)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 1/1. (PMID:23838601)
- 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: 1/1. (PMID:15499950)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 9/15. (PMID:16765077;PMID:20159436;PMID:15210538;PMID:19353847;PMID:18924171;PMID:14994243;PMID:10749987;PMID:15499950)
- 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:31844624)
- Stridor (HP:0010307): Stridor is a high pitched sound resulting from turbulent air flow in the upper airway. Evidence: PCS. Frequency: 1/1. (PMID:14994243)
- 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: 3/5. (PMID:10545952;PMID:10749987;PMID:31844624)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:34746378)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: PCS. Frequency: 2/2. (PMID:31844624)
- Abnormal brainstem morphology (HP:0002363): An anomaly of the brainstem. Evidence: PCS. Frequency: 1/1. (PMID:18924171)
- Abnormal corpus callosum morphology (HP:0001273): Abnormality of the corpus callosum. Evidence: PCS. Frequency: 1/1. (PMID:18924171)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 4/5. (PMID:20159436;PMID:23838601;PMID:10545952)
- Elevated lactate:pyruvate ratio (HP:0032653): An abnormal increase in the molar ratio of lactate to pyruvate in the blood circulation. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 8/10. (PMID:23838601;PMID:10545952;PMID:15499950)
- Sensorimotor neuropathy (HP:0007141). Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Abnormal periventricular white matter morphology (HP:0002518): A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles. Evidence: PCS. Frequency: 1/1. (PMID:18924171)
- 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: 10/11. (PMID:16765077;PMID:10749987;PMID:15499950;PMID:35112411)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- 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: 2/4. (PMID:20159436;PMID:10545952)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 3/4. (PMID:29351582;PMID:31844624;PMID:35112411)
- Limited extraocular movements (HP:0007941): Limited mobility of the eye within its socket. Evidence: IEA. (OMIM:604377)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 9/9. (PMID:23407777;PMID:17187620;PMID:10749987;PMID:15499950)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: PCS. Frequency: 5/5. (PMID:10805329;PMID:10749987)
- Right ventricular hypertrophy (HP:0001667): In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal. Evidence: PCS. Frequency: 1/2. (PMID:14994243;PMID:35112411)
- Cerebellar vermis atrophy (HP:0006855): Wasting (atrophy) of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:31844624)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/4. (PMID:29351582;PMID:35112411)
- 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: 1/2. (PMID:35112411)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/1. (PMID:23838601)
- Respiratory distress (HP:0002098): Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea. Evidence: PCS. Frequency: 6/8. (PMID:10805329;PMID:15210538;PMID:19353847;PMID:10545952)
- Impaired vibratory sensation (HP:0002495): A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient. Evidence: PCS. Frequency: 2/4. (PMID:29351582;PMID:35112411)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 3/3. (PMID:34746378;PMID:18924171;PMID:14994243)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: PCS. Frequency: 1/1. (PMID:17187620)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 3/3. (PMID:10545952;PMID:31844624)
- Hemeralopia (HP:0012047): A visual defect characterized by the inability to see as clearly in bright light as in dim light. The word hemeralopia literally means day blindness. Evidence: PCS. Frequency: 1/1. (PMID:34746378)
- 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: 3/4. (PMID:16765077;PMID:23838601;PMID:29351582)
- 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: 4/4. (PMID:16765077;PMID:10805329)
- Neuronal loss in central nervous system (HP:0002529). Evidence: PCS. Frequency: 2/2. (PMID:10545952)
- 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: TAS. (OMIM:604377)
- 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:34746378)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- 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: 1/1. (PMID:34746378)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: PCS. Frequency: 3/3. (PMID:10805329)
- 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: 1/3. (PMID:10545952)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:23838601)
- 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: 1/2. (PMID:35112411)
- 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: 4/5. (PMID:18924171;PMID:10749987;PMID:35112411)
- 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: 2/2. (PMID:31844624)
- 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: 20/23. (PMID:20159436;PMID:23407777;PMID:10805329;PMID:19353847;PMID:15210538;PMID:23838601;PMID:10545952;PMID:18924171;PMID:14994243;PMID:17187620;PMID:10749987;PMID:15499950)
- 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:34746378;PMID:23838601)
- Limited ankle dorsiflexion (HP:0033526): Reduced ability to move the foot up toward the shin. Evidence: PCS. Frequency: 1/1. (PMID:35112411)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/4. (PMID:31844624;PMID:35112411)
- Facial-lingual fasciculations (HP:0007089): Fasciculations affecting the tongue muscle and the musculature of the face. Evidence: PCS. Frequency: 1/2. (PMID:29351582)
- Motor axonal neuropathy (HP:0007002): Progressive impairment of function of motor axons with muscle weakness, atrophy, and cramps. The deficits are length-dependent, meaning that muscles innervated by the longest nerves are affected first, so that for instance the arms are affected at a later age than the onset of deficits involving the lower leg. Evidence: PCS. Frequency: 2/2. (PMID:23407777;PMID:29351582)
- Hypoplastic toenails (HP:0001800): Underdevelopment of the toenail. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 3/3. (PMID:10545952)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 1/2. (PMID:29351582)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 9/10. (PMID:10805329;PMID:31844624;PMID:15499950;PMID:35112411)
- Inspiratory stridor (HP:0005348): Inspiratory stridor is a high pitched sound upon inspiration that is generally related to laryngeal abnormalities. Evidence: PCS. Frequency: 7/9. (PMID:23407777;PMID:10545952;PMID:18924171;PMID:10749987;PMID:15499950)
- Heart murmur (HP:0030148): An extra or unusual sound heard during a heartbeat caused vibrations resulting from the flow of blood through the heart. Evidence: PCS. Frequency: 1/1. (PMID:15210538)
- Bradycardia (HP:0001662): A slower than normal heart rate (in adults, slower than 60 beats per minute). Evidence: PCS. Frequency: 1/2. (PMID:18924171;PMID:35112411)
- Memory impairment (HP:0002354): An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness. Evidence: PCS. Frequency: 1/1. (PMID:34746378)
- 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: 3/5. (PMID:16765077;PMID:20159436;PMID:10545952)
- 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:29351582)
- 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: 13/14. (PMID:23838601;PMID:10545952;PMID:35112411;PMID:23364397)
- Focal cortical dysplasia (HP:0032046): A type of malformation of cortical development that primarily affects areas of neocortex. It can be identified on conventional magnetic resonance imaging as focal cortical thickening, abnormal gyration, and blurring between gray and white matter, often associated with clusters of heterotopic neurons. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- 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: 3/4. (PMID:29351582;PMID:31844624;PMID:35112411)
- Hand muscle atrophy (HP:0009130): Muscular atrophy involving the muscles of the hand. Evidence: PCS. Frequency: 1/1. (PMID:35112411)
- Limb hypertonia (HP:0002509). Evidence: PCS. Frequency: 1/1. (PMID:23364397)
- Cardiorespiratory arrest (HP:0006543). Evidence: PCS. Frequency: 3/3. (PMID:10805329)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/2. (PMID:29351582)
- Respiratory insufficiency due to muscle weakness (HP:0002747). Evidence: PCS. Frequency: 2/2. (PMID:23407777;PMID:15210538)
- Absent Achilles reflex (HP:0003438): Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed. Evidence: PCS. Frequency: 5/7. (PMID:19353847;PMID:29351582;PMID:31844624;PMID:35112411)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: PCS. Frequency: 1/1. (PMID:34746378)
- 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:10545952)
- 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: 16/17. (PMID:16765077;PMID:20159436;PMID:10805329;PMID:23407777;PMID:15210538;PMID:18924171;PMID:14994243;PMID:17187620;PMID:15499950;PMID:35112411)
- Malignant hyperthermia (HP:0002047): Malignant hyperthermia is characterized by a rapid increase in temperature to 39-42 degrees C. Malignant hyperthermia may occur in response to either inhalational anesthetics such as halothane, to muscle relaxants such as succinylcholine, or to exercise. Evidence: PCS. Frequency: 3/3. (PMID:23364397)
- Abnormal calvaria morphology (HP:0002683): Abnormality of the morphology (structure) of the calvaria (skullcap), that is, of that part of the skull that is made up of the superior portions of the frontal bone, occipital bone, and parietal bones and covers the cranial cavity that contains the brain. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- 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: PCS. Frequency: 2/2. (PMID:29351582)
- 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: 1/3. (PMID:29351582;PMID:35112411)
- Abnormal circulating creatine kinase activity (HP:0040081): Any deviation from the normal activity of creatine kinase in the blood circulation. Evidence: PCS. Frequency: 1/3. (PMID:34746378;PMID:23838601;PMID:29351582)
- Focal T2 hyperintense basal ganglia lesion (HP:0007183): A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- 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:20159436;PMID:23838601)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 2/3. (PMID:29351582;PMID:35112411)
- Lacticaciduria (HP:0003648): An increased concentration of lactic acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:23838601)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 8/9. (PMID:16765077;PMID:20159436;PMID:23407777;PMID:15210538;PMID:10545952;PMID:14994243;PMID:35112411)
- Basal ganglia gliosis (HP:0006999): Focal proliferation of glial cells in the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:10545952)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- Cardiomegaly (HP:0001640): Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. Evidence: PCS. Frequency: 1/1. (PMID:23407777)
- Increased circulating pyruvate concentration (HP:0003542): The concentration of pyruvate in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- 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: 1/1. (PMID:29351582)
- Limb dystonia (HP:0002451): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: PCS. Frequency: 4/6. (PMID:10805329;PMID:10545952)
- Upper limb hypertonia (HP:0200049): Increased muscle tone observed in the arms of the affected person. Evidence: PCS. Frequency: 1/1. (PMID:23407777)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 3/3. (PMID:10545952)
- 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:34746378)
- Persistent fever (HP:0033399): Fever that persists longer than expected for an acute infectious disease. No precise threshold exists, and the clinical interpretation of fever is context-dependent, but as a rule of thumb, this term refers to fever that persists longer than 2-3 weeks. Evidence: PCS. Frequency: 3/3. (PMID:23364397)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: PCS. Frequency: 18/22. (PMID:16765077;PMID:20159436;PMID:10805329;PMID:15210538;PMID:19353847;PMID:10545952;PMID:18924171;PMID:14994243;PMID:17187620;PMID:10749987;PMID:15499950)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/1. (PMID:20159436)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: PCS. Frequency: 3/3. (PMID:10805329)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: PCS. Frequency: 4/5. (PMID:10805329;PMID:14994243;PMID:35112411)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: PCS. Frequency: 1/3. (PMID:10545952)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/2. (PMID:16765077;PMID:19353847)
- Distal lower limb amyotrophy (HP:0008944): Muscular atrophy of distal leg muscles. Evidence: PCS. Frequency: 3/4. (PMID:29351582;PMID:35112411)
- Decreased total neutrophil count (HP:0001875): Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/1. (PMID:17187620)
These phenotypes are associated with the disease cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (OMIM:604377).