Phenotypes associated with the disease developmental and epileptic encephalopathy, 41 (OMIM:617105, an entry in Online Mendelian Inheritance in Man):
- Bilateral tonic-clonic seizure (HP:0002069, a Human Phenotype Ontology term): 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: 1/3. (PMID:27476654)
- Lethargy (HP:0001254, a Human Phenotype Ontology term): 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: IEA. (OMIM:617105)
- Nephrocalcinosis (HP:0000121, a Human Phenotype Ontology term): Nephrocalcinosis is the deposition of calcium salts in renal parenchyma. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Hypsarrhythmia (HP:0002521, a Human Phenotype Ontology term): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Delayed CNS myelination (HP:0002188, a Human Phenotype Ontology term): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Inability to walk (HP:0002540, a Human Phenotype Ontology term): Incapability to ambulate. Evidence: IEA. (OMIM:617105)
- Delayed eruption of teeth (HP:0000684, a Human Phenotype Ontology term): Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Flexion contracture (HP:0001371, a Human Phenotype Ontology term): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: TAS. (OMIM:617105)
- Profound intellectual disability (HP:0002187, a Human Phenotype Ontology term): 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: 2/3. (PMID:27476654)
- Infantile onset (HP:0003593, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Generalized hypotonia (HP:0001290, a Human Phenotype Ontology term): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Myoclonic seizure (HP:0032794, a Human Phenotype Ontology term): A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 3/3. (PMID:27476654)
- Severe intellectual disability (HP:0010864, a Human Phenotype Ontology term): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Focal tonic seizure (HP:0011167, a Human Phenotype Ontology term): A type of focal motor seizure characterized by sustained increase in muscle contraction, lasting a few seconds to minutes. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Irritability (HP:0000737, a Human Phenotype Ontology term): 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: IEA. (OMIM:617105)
- Neonatal onset (HP:0003623, a Human Phenotype Ontology term): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Kyphoscoliosis (HP:0002751, a Human Phenotype Ontology term): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: TAS. (OMIM:617105)
- Axial hypotonia (HP:0008936, a Human Phenotype Ontology term): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Cerebral atrophy (HP:0002059, a Human Phenotype Ontology term): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Microcephaly (HP:0000252, a Human Phenotype Ontology term): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Absent speech (HP:0001344, a Human Phenotype Ontology term): Complete lack of development of speech and language abilities. Evidence: IEA. (OMIM:617105)
- EEG abnormality (HP:0002353, a Human Phenotype Ontology term): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: PCS. Frequency: 3/3. (PMID:27476654)
- Developmental regression (HP:0002376, a Human Phenotype Ontology term): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Occasional (HP:0040283, a Human Phenotype Ontology term). (OMIM:617105)
- Hypoplasia of the corpus callosum (HP:0002079, a Human Phenotype Ontology term): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Babinski sign (HP:0003487, a Human Phenotype Ontology term): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Feeding difficulties (HP:0011968, a Human Phenotype Ontology term): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: IEA. (OMIM:617105)
- Generalized tonic seizure (HP:0010818, a Human Phenotype Ontology term): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Global developmental delay (HP:0001263, a Human Phenotype Ontology term): 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:27476654)
- Tetraparesis (HP:0002273, a Human Phenotype Ontology term): Weakness of all four limbs. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Status epilepticus without prominent motor symptoms (HP:0031475, a Human Phenotype Ontology term): There is inconclusive evidence to precisely define the duration of the seizure; however, based on current evidence an operational threshold of 10 minutes is appropriate as beyond this a seizure is likely to be more prolonged. The individual may or may not be aware or in coma. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Myoclonic status epilepticus (HP:0032667, a Human Phenotype Ontology term): A type of motor status epilepticus with repeating bilateral sudden brief (less than 100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography. Evidence: PCS. Frequency: 2/3. (PMID:27476654)
- Epileptic spasm (HP:0011097, a Human Phenotype Ontology term): A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur: Grimacing, head nodding, or subtle eye movements. Epileptic spasms frequently occur in clusters. Infantile spasms are the best known form, but spasms can occur at all ages. Evidence: PCS. Frequency: 1/3. (PMID:27476654)
- Epileptic encephalopathy (HP:0200134, a Human Phenotype Ontology term): 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: 3/3. (PMID:27476654)
- Spasticity (HP:0001257, a Human Phenotype Ontology term): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. Frequency: Occasional (HP:0040283, a Human Phenotype Ontology term). (OMIM:617105)
- Autosomal dominant inheritance (HP:0000006, a Human Phenotype Ontology term): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:27476654)