Phenotypes associated with the disease neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (OMIM:616276):
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 3/7. (PMID:25658047;PMID:26185144)
- 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: 1/1. (PMID:22368301)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/5. (PMID:25658047)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 10/14. (PMID:25658047;PMID:31396399;PMID:26185144;PMID:30659264)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: PCS. Frequency: 1/1. (PMID:22368301)
- 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:30659264)
- Focal impaired awareness seizure (HP:0002384): Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure. Evidence: PCS. Frequency: 1/1. (PMID:30659264)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 1/5. (PMID:31396399)
- 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: 10/13. (PMID:25658047;PMID:30659264;PMID:31396399)
- Moderate to late preterm birth (HP:0025664): Birth at 32 to 36 completed weeks of gestation. Evidence: PCS. Frequency: 2/11. (PMID:25658047;PMID:26185144)
- 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: 3/4. (PMID:31396399)
- 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: 1/1. Onset: Neonatal onset (HP:0003623). (PMID:22368301)
- 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: 1/1. (PMID:25658047)
- 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: 7/11. (PMID:31396399)
- 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: 5/5. (PMID:26185144)
- 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: 1/1. (PMID:33704555)
- 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: 2/3. (PMID:33704555;PMID:25658047)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 8/16. (PMID:25658047;PMID:31396399)
- 2-hydroxyglutarate aciduria (HP:0032278): The concentration of 2-hydroxyglutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 4/10. (PMID:25658047;PMID:26185144)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 1/1. (PMID:22368301)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 4/6. (PMID:26185144)
- Severely reduced left ventricular ejection fraction (HP:0012666): A large reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at over 50 percent, and a severe reduction is defined as less than 30 percent. Evidence: PCS. Frequency: 1/2. (PMID:25658047)
- 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: 8/12. (PMID:33704555;PMID:25658047;PMID:31396399)
- 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:30659264)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/2. (PMID:33704555)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 3/5. (PMID:25658047)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 3/6. (PMID:31396399)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 1/1. (PMID:22368301)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: PCS. Frequency: 0/2. (PMID:25658047)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 5/13. (PMID:31396399;PMID:30659264)
- Focal hemiclonic seizure (HP:0006813): A type of focal clonic seizure characterized by sustained rhythmic jerking rapidly involves one side of the body at seizure onset. Evidence: PCS. Frequency: 1/12. (PMID:33704555;PMID:25658047;PMID:26185144)
- Bradycardia (HP:0001662): A slower than normal heart rate (in adults, slower than 60 beats per minute). Evidence: PCS. Frequency: 1/3. (PMID:25658047)
- Acrocyanosis (HP:0001063): Bluish discoloration of the skin of the hands or feet. Evidence: PCS. Frequency: 1/3. (PMID:25658047)
- 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: 2/3. (PMID:33704555;PMID:30659264;PMID:26185144)
- 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: 10/15. (PMID:33704555;PMID:31396399;PMID:30659264;PMID:26185144)
- 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: 13/13. (PMID:25658047;PMID:30659264;PMID:31396399)
- 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: 20/24. (PMID:25658047;PMID:31396399;PMID:26185144;PMID:30659264)
- 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:22368301)
- Cerebral infarct (HP:0025722): A necrotic lesion in the cerebrum resulting from a sudden insufficiency of arterial or venous blood supply due to emboli, thrombi or mechanical factors. Evidence: PCS. Frequency: 2/3. (PMID:31396399)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/5. (PMID:31396399)
- 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: 4/11. (PMID:33704555;PMID:25658047;PMID:31396399)
- 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: 1/2. (PMID:25658047)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 9/23. (PMID:25658047;PMID:22368301;PMID:31396399;PMID:26185144)
- 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:33704555)
- 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: 4/11. (PMID:33704555;PMID:25658047;PMID:31396399)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 1/5. (PMID:31396399)
- Hypoplastic left ventricle (HP:0004383): A severe congenital heart defect characterized by underdevelopment of the left ventricle. Evidence: IEA. Frequency: Very rare (HP:0040284). (OMIM:616276)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 2/3. (PMID:33704555;PMID:25658047)
- 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:30659264)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 1/1. (PMID:22368301)
- 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: 5/11. (PMID:31396399)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 2/2. (PMID:30659264)
- 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: 1/3. (PMID:33704555;PMID:30659264;PMID:26185144)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 0/5. (PMID:25658047)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 6/9. (PMID:31396399)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 7/8. (PMID:25658047;PMID:26185144)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/2. (PMID:33704555)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:25658047)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 11/18. (PMID:33704555;PMID:25658047;PMID:31396399;PMID:26185144)
- Distal arthrogryposis (HP:0005684): An inherited primary limb malformation disorder characterized by congenital contractures of two or more different body areas and without primary neurologic and/or muscle disease that affects limb function. Evidence: PCS. Frequency: 2/4. (PMID:25658047)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 3/3. (PMID:33704555;PMID:25658047)
- EEG with burst suppression (HP:0010851): The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes. Evidence: PCS. Frequency: 2/2. (PMID:33704555)
- Postural instability (HP:0002172): A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps. Evidence: PCS. Frequency: 1/1. (PMID:25658047)
- Decreased level of coenzyme Q10 in skeletal muscle (HP:0034369): Reduced amount of coenzyme Q10,a naturally occurring quinone, in skeletal muscle tissue. Evidence: PCS. Frequency: 5/5. (PMID:25658047;PMID:26185144)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 3/3. Onset: Neonatal onset (HP:0003623). (PMID:25658047)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 2/2. (PMID:30659264)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 4/4. (PMID:26185144)
- 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: 4/12. (PMID:25658047;PMID:30659264;PMID:31396399)
- Epileptic encephalopathy (HP:0200134): A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. Evidence: PCS. Frequency: 1/3. (PMID:25658047)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/9. (PMID:25658047;PMID:26185144)
- Elevated circulating creatinine concentration (HP:0003259): An increased amount of creatinine in the blood. Evidence: PCS. Frequency: 0/6. (PMID:25658047;PMID:30659264)