- 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: 4/4. (PMID:37421948)
- Delayed CNS myelination (HP:0002188, a Human Phenotype Ontology term): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Recurrent lower respiratory tract infections (HP:0002783, a Human Phenotype Ontology term): An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections. Evidence: PCS. Frequency: 2/2. (PMID:37421948)
- Focal impaired awareness seizure (HP:0002384, a Human Phenotype Ontology term): 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: 9/9. (PMID:37421948)
- 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: PCS. Frequency: 1/1. (PMID:37421948)
- Gait ataxia (HP:0002066, a Human Phenotype Ontology term): 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: 1/1. (PMID:37421948)
- Hypotonia (HP:0001252, a Human Phenotype Ontology term): 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:37421948)
- Ataxia (HP:0001251, a Human Phenotype Ontology term): 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: 1/1. (PMID:37421948)
- 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: 8/17. (PMID:37421948)
- 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: 1/1. (PMID:37421948)
- Generalized hypotonia (HP:0001290, a Human Phenotype Ontology term): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 6/6. (PMID:37421948)
- Thin corpus callosum (HP:0033725, a Human Phenotype Ontology term): 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: 14/14. (PMID:37421948)
- Infantile spasms (HP:0012469, a Human Phenotype Ontology term): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 3/3. (PMID:37421948)
- Increased total monocyte count (HP:0012311, a Human Phenotype Ontology term): Abnormal increase of absolute number of monocytes in the blood, per microlitre, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Moderate global developmental delay (HP:0011343, a Human Phenotype Ontology term): A moderate delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 2/2. (PMID:37421948)
- Nystagmus (HP:0000639, a Human Phenotype Ontology term): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 7/7. (PMID:37421948)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/17. (PMID:37421948)
- Reticulocytosis (HP:0001923, a Human Phenotype Ontology term): An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Laryngomalacia (HP:0001601, a Human Phenotype Ontology term): Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Jaundice (HP:0000952, a Human Phenotype Ontology term): 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:37421948)
- Retinal dystrophy (HP:0000556, a Human Phenotype Ontology term): Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- 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: 4/17. (PMID:37421948)
- Increased red cell osmotic fragility (HP:0005502, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 0/3. (PMID:37421948)
- Microcephaly (HP:0000252, a Human Phenotype Ontology term): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- 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: 17/17. (PMID:37421948)
- Dysarthria (HP:0001260, a Human Phenotype Ontology term): 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:37421948)
- Tetraparesis (HP:0002273, a Human Phenotype Ontology term): Weakness of all four limbs. Evidence: PCS. Frequency: 10/10. (PMID:37421948)
- Abnormal CNS myelination (HP:0011400, a Human Phenotype Ontology term): An abnormality of myelination of nerves in the central nervous system. Evidence: PCS. Frequency: 5/5. (PMID:37421948)
- Profound global developmental delay (HP:0012736, a Human Phenotype Ontology term): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 13/13. (PMID:37421948)
- Dyskinesia (HP:0100660, a Human Phenotype Ontology term): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- 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: 5/5. (PMID:37421948)
- Autistic behavior (HP:0000729, a Human Phenotype Ontology term): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: PCS. Frequency: 2/2. (PMID:37421948)
- Hyperbilirubinemia (HP:0002904, a Human Phenotype Ontology term): An increased amount of bilirubin in the blood. Evidence: PCS. Frequency: 2/2. (PMID:37421948)
- Macrocytic anemia (HP:0001972, a Human Phenotype Ontology term): A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH). Evidence: PCS. Frequency: 5/5. (PMID:37421948)
- Focal-onset seizure (HP:0007359, a Human Phenotype Ontology term): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Tremor (HP:0001337, a Human Phenotype Ontology term): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- 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:37421948)
- Congenital onset (HP:0003577, a Human Phenotype Ontology term): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/17. (PMID:37421948)
- Pseudobulbar signs (HP:0002200, a Human Phenotype Ontology term): Pseudobulbar signs result from injury to an upper motor neuron lesion to the corticobulbar pathways in the pyramidal tract. Patients have difficulty chewing, swallowing and demonstrate slurred speech (often initial presentation) as well as abnormal behavioral symptoms such as inappropriate emotional outbursts of uncontrolled laughter or weeping etc. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Alopecia (HP:0001596, a Human Phenotype Ontology term): A noncongenital process of hair loss, which may progress to partial or complete baldness. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Cerebellar atrophy (HP:0001272, a Human Phenotype Ontology term): 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: 8/8. (PMID:37421948)
- Cerebral cortical atrophy (HP:0002120, a Human Phenotype Ontology term): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Anemia (HP:0001903, a Human Phenotype Ontology term): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 3/4. (PMID:37421948)
- Cerebral visual impairment (HP:0100704, a Human Phenotype Ontology term): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: PCS. Frequency: 7/7. (PMID:37421948)
- Respiratory failure (HP:0002878, a Human Phenotype Ontology term): 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: 1/1. (PMID:37421948)
- Lower limb hypertonia (HP:0006895, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Prolonged neonatal jaundice (HP:0006579, a Human Phenotype Ontology term): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: PCS. Frequency: 3/3. (PMID:37421948)
- Osteomyelitis (HP:0002754, a Human Phenotype Ontology term): Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Lateral ventricle dilatation (HP:0006956, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 3/3. (PMID:37421948)
- Dysphagia (HP:0002015, a Human Phenotype Ontology term): Difficulty in swallowing. Evidence: PCS. Frequency: 11/11. (PMID:37421948)
- Vesicoureteral reflux (HP:0000076, a Human Phenotype Ontology term): Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Status epilepticus (HP:0002133, a Human Phenotype Ontology term): 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: 3/3. (PMID:37421948)
- Colpocephaly (HP:0030048, a Human Phenotype Ontology term): Colpocephaly is an anatomic finding in the brain manifested by occipital horns that are disproportionately enlarged in comparison with other parts of the lateral ventricles. Evidence: PCS. Frequency: 2/2. (PMID:37421948)
- Febrile seizure (within the age range of 3 months to 6 years) (HP:0002373, a Human Phenotype Ontology term): 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: 2/2. (PMID:37421948)
- Limb dystonia (HP:0002451, a Human Phenotype Ontology term): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- 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: 1/1. (PMID:37421948)
- Severe global developmental delay (HP:0011344, a Human Phenotype Ontology term): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Cholecystitis (HP:0001082, a Human Phenotype Ontology term): The presence of inflammatory changes in the gallbladder. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Extra-axial cerebrospinal fluid accumulation (HP:0012510, a Human Phenotype Ontology term): An increased amount of cerebrospinal fluid (CSF) in the subarachnoid space. Evidence: PCS. Frequency: 5/5. (PMID:37421948)
- Conjunctival icterus (HP:0032106, a Human Phenotype Ontology term): Conjunctival icterus is a condition where there is yellowing of the whites of the eyes. This is most commonly seen in patients who have liver disease. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Reduced cerebral white matter volume (HP:0034295, a Human Phenotype Ontology term): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Aplastic anemia (HP:0001915, a Human Phenotype Ontology term): Aplastic anemia is defined as pancytopenia with a hypocellular marrow. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Visual impairment (HP:0000505, a Human Phenotype Ontology term): 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: 3/3. (PMID:37421948)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334, a Human Phenotype Ontology term): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: PCS. Frequency: 4/4. (PMID:37421948)
- Plagiocephaly (HP:0001357, a Human Phenotype Ontology term): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Thrombocytopenia (HP:0001873, a Human Phenotype Ontology term): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/1. (PMID:37421948)
- Hepatosplenomegaly (HP:0001433, a Human Phenotype Ontology term): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 2/3. (PMID:37421948)
These phenotypes are associated with the disease developmental and epileptic encephalopathy 118 (OMIM:621250, an entry in Online Mendelian Inheritance in Man).