Phenotypes associated with the disease developmental and epileptic encephalopathy, 39 (OMIM:612949):
- 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: 2/3. (PMID:24515575;PMID:19641205)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Narrow palate (HP:0000189): Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective). Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Jejunal atresia (HP:0005235): A developmental defect resulting in abnormal closure, or atresia of the tubular structure of the jejunum. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- 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: 2/2. (PMID:24515575)
- 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: 1/2. (PMID:24515575)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Cerebral hypomyelination (HP:0006808): Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the white matter of the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/3. (PMID:24515575;PMID:19641205)
- Reduced brain N-acetyl aspartate level by MRS (HP:0012708): A decrease in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Frontal hirsutism (HP:0011335): Excessive amount of hair growth on forehead. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Febrile status epilepticus (HP:0032656): A seizure lasting 30 minutes without fully regaining consciousness, provoked by fever (temperature greater than 38.0 degrees Celcius) at the time of seizure-onset, without a prior history of afebrile seizure and with no evidence of an acute central nervous system infection or insult. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Darwin tubercle of helix (HP:0011261): Small expansion of the helical fold at the junction of the superior and descending portions of the helix. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 2/2. (PMID:24515575)
- Type 1 muscle fiber predominance (HP:0003803): An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy). Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- 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:24515575)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Delayed ability to roll over (HP:0032989): Delayed achievement of the ability to roll front to back and back to front. Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Flat occiput (HP:0005469): Reduced convexity of the occiput (posterior part of skull). Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 3/3. (PMID:24515575;PMID:19641205)
- 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: 1/2. (PMID:24515575)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 2/2. (PMID:24515575)
- 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: 1/2. (PMID:24515575)
- Generalized hirsutism (HP:0002230): Abnormally increased hair growth over much of the entire body. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 3/3. (PMID:24515575;PMID:19641205)
- 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: 1/1. (PMID:19641205)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 2/2. (PMID:24515575)
- Persistent head lag (HP:0032988): The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows: 0 = head drops and stays back, 1 = tries to lift head but drops it back, 2 = able to lift head slightly, 3 = lifts head in line with body, and 4 = head in front of body. This term applies if head lag persists beyond an expected age at a level of 0 or 1. Persistent head lag beyond age 4 mo has been linked to poor outcomes. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Tonic seizure (HP:0032792): A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening. Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- Generalized hyperreflexia (HP:0007034). Evidence: PCS. Frequency: 1/1. (PMID:19641205)
- 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:19641205)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- 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: 2/3. (PMID:24515575;PMID:19641205)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Chronic otitis media (HP:0000389): Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- Oval face (HP:0000300): A face with a rounded and slightly elongated outline. Evidence: PCS. Frequency: 1/2. (PMID:24515575)
- 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: 1/1. (PMID:19641205)
- 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: 1/1. (PMID:19641205)
- 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: 1/2. (PMID:24515575)
- 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:19641205)