- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: TAS. (OMIM:614959)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: PCS. (PMID:24029078)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 3/8. (PMID:24029078;PMID:23086397)
- Focal clonic seizure (HP:0002266): A focal clonic seizure is a type of focal motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/5. (PMID:24029078;PMID:23086397)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 3/8. (PMID:24029078;PMID:23086397)
- 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: 12/12. (PMID:23086397)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 4/8. (PMID:24029078;PMID:23086397)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 4/8. (PMID:24029078;PMID:23086397)
- Focal autonomic seizure with palpitations/tachycardia/bradycardia/asystole (HP:0032773): A type of focal autonomic seizure characterized by changes in heart rate as the initial semiological feature. Evidence: PCS. Frequency: 2/8. (PMID:24029078;PMID:23086397)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 1/1. (PMID:24029078)
- Generalized-onset motor seizure (HP:0032677): A generalized motor seizure is a type of generalized-onset seizure with predominantly motor (involving musculature) signs. The motor event could consist of an increase (positive) or decrease (negative) in muscle contraction to produce a movement. Evidence: PCS. Frequency: 1/1. (PMID:24029078)
- 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: 3/8. (PMID:24029078;PMID:23086397)
- Interictal epileptiform activity (HP:0011182): Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure. Evidence: PCS. Frequency: 2/2. (PMID:24029078)
- Focal tonic seizure (HP:0011167): A type of focal motor seizure characterized by sustained increase in muscle contraction, lasting a few seconds to minutes. Evidence: PCS. Frequency: 3/5. (PMID:24029078;PMID:23086397)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: Occasional (HP:0040283). (PMID:23086397)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. (OMIM:614959)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 4/6. (PMID:23086397)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 4/8. (PMID:24029078;PMID:23086397)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 4/8. (PMID:24029078;PMID:23086397)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 2/8. (PMID:24029078;PMID:23086397)
- 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: TAS. (OMIM:614959)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/2. (PMID:24029078)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 7/12. (PMID:23086397)
- Inability to walk by childhood/adolescence (HP:0006915). Evidence: PCS. Frequency: 3/8. (PMID:24029078;PMID:23086397)
- Generalized tonic seizure (HP:0010818): 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: 3/8. (PMID:24029078;PMID:23086397)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: TAS. (OMIM:614959)
- Generalized clonic seizure (HP:0011169): Generalized clonic seizure is a type of generalized motor seizure characterized by sustained bilateral jerking, either symmetric or asymmetric, that is regularly repetitive and involves the same muscle groups. Evidence: PCS. Frequency: 1/8. (PMID:24029078;PMID:23086397)
- Profound global developmental delay (HP:0012736): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 6/8. (PMID:24029078;PMID:23086397)
- Focal autonomic seizure (HP:0011154): An autonomic seizure is a type of focal non-motor seizure characterized by alteration of autonomic nervous system function as the initial semiological feature. Evidence: PCS. Frequency: 5/12. (PMID:23086397)
- Focal motor seizure (HP:0011153): A type of focal-onset seizure characterized by a motor sign as its initial semiological manifestation. Evidence: PCS. Frequency: 4/4. (PMID:24029078;PMID:23086397)
- Neuronal loss in central nervous system (HP:0002529). Evidence: TAS. (OMIM:614959)
- 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: 8/8. (PMID:24029078;PMID:23086397)
- 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: TAS. (OMIM:614959)
- Autosomal dominant inheritance (HP:0000006): 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:23086397)
- 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: TAS. (OMIM:614959)
These phenotypes are associated with the disease developmental and epileptic encephalopathy, 14 (OMIM:614959).