- 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: 8/8. (PMID:36214804)
- 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: 4/14. (PMID:36214804)
- Square face (HP:0000321): Facial contours, as viewed from the front, show a broad upper face/cranium and lower face/mandible, creating a square appearance. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 2/2. (PMID:36214804)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 4/13. (PMID:36214804)
- 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: 4/4. (PMID:36214804)
- Trigonocephaly (HP:0000243): Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- 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: 2/13. (PMID:36214804)
- 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: 2/2. (PMID:36214804)
- 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: 1/1. (PMID:36214804)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: PCS. Frequency: 3/14. (PMID:36214804)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/10. (PMID:36214804;PMID:38513146)
- Myoclonic seizure (HP:0032794): 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: 2/2. (PMID:36214804)
- 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: 1/1. (PMID:36214804)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/9. (PMID:36214804)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 8/13. (PMID:36214804)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- 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: 6/14. (PMID:36214804)
- Vascular dilatation (HP:0002617): An abnormal increase in the diameter of an artery or vein, either as a diffuse dilatation or as a localized, sac-like outpouching of the vessel wall (aneurysm). Evidence: PCS. Frequency: 0/12. (PMID:36214804)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: PCS. Frequency: 9/12. (PMID:36214804)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Pulmonic stenosis (HP:0001642): A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis). Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/9. (PMID:36214804)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 4/14. (PMID:36214804)
- Tall stature (HP:0000098): A height above that which is expected according to age and gender norms. Evidence: PCS. Frequency: 2/13. (PMID:36214804)
- Interictal EEG abnormality (HP:0025373): Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge. Evidence: PCS. Frequency: 9/11. (PMID:36214804)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 6/6. (PMID:36214804)
- 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: 2/2. (PMID:36214804;PMID:38513146)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Dystonic gait (HP:0031954): Dystonic gait disorders frequently appear bizarre, particularly because activity increases dystonic tonus and posture. The abnormal posture of the foot in dystonic gait typically involves inversion, plantar flexion and tonic extension of the big toe. In many patients complex types of walking, such as walking backwards and running are paradoxically less impaired than walking forward and may seem completely unaffected. Sensory tricks, for instance, if the affected individual rests a hand on his or her neck, may improve or even normalize dystonic gait in some patients. Evidence: PCS. Frequency: 1/13. (PMID:36214804)
- Recurrent hand flapping (HP:0100023): A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically. Evidence: PCS. Frequency: 8/8. (PMID:36214804)
- Appendicular spasticity (HP:0034353): A type of spasticity that affects one or more limbs (arms or legs). Evidence: PCS. Frequency: 2/2. (PMID:36214804)
- Vertebral artery tortuosity (HP:0033981): Abnormal tortuous (i.e., twisted) form of the vertebral arteries. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Autistic behavior (HP:0000729): 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: 12/14. (PMID:36214804)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 3/11. (PMID:36214804)
- Facial hemangioma (HP:0000329): Hemangioma, a benign tumor of the vascular endothelial cells, occurring in the face. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 8/14. (PMID:36214804)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: PCS. Frequency: 5/13. (PMID:36214804)
- 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: 0/11. (PMID:36214804)
- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: PCS. Frequency: 2/11. (PMID:36214804)
- 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:36214804)
- Hypsarrhythmia (HP:0002521): 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: 1/1. (PMID:38513146)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 2/15. (PMID:36214804;PMID:38513146)
- Jumping (HP:5200134): An excessive frequency of jumping in place. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Distal joint hypermobility (HP:0020152): Lack of stability of a distal joint (e.g., finger). Evidence: PCS. Frequency: 4/14. (PMID:36214804)
- Vein of Galen aneurysmal malformation (HP:0030713): Vein of Galen aneurysmal malformation is a choroidal type of arteriovenous malformation that develops between 6 and 11 weeks of gestation. It results from 1 or more arteriovenous fistulas shunting blood toward the prosencephalic vein of Markowski, the embryonic precursor of the vein of Galen. This abnormal shunt leads to progressive dilation of the vein and prevents its involution and subsequent development into the vein of Galen. Evidence: PCS. Frequency: 1/13. (PMID:36214804)
- Severe intellectual disability (HP:0010864): 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: 7/7. (PMID:36214804)
- Stereotypical body rocking (HP:0012172): Habitual repetitive movement of the entire body, front to back or side to side. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: PCS. Frequency: 11/14. (PMID:36214804)
- Inferior cerebellar vermis hypoplasia (HP:0007068): Underdevelopment of the inferior portion of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Motor stereotypy (HP:0000733): Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose. Evidence: PCS. Frequency: 2/2. (PMID:36214804)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 4/14. (PMID:36214804)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 2/14. (PMID:36214804)
- Thick lower lip vermilion (HP:0000179): Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective). Evidence: PCS. Frequency: 6/14. (PMID:36214804)
- 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:38513146)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 6/12. (PMID:36214804)
- 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: 3/3. (PMID:36214804)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 8/8. (PMID:36214804)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/14. (PMID:36214804)
- 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: 6/11. (PMID:36214804)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 4/13. (PMID:36214804)
- Atonic seizure (HP:0010819): Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature. Evidence: PCS. Frequency: 2/2. (PMID:36214804)
- Small forehead (HP:0000350): The presence of a forehead that is abnormally small. Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Narrow palpebral fissure (HP:0045025): Reduction in the vertical distance between the upper and lower eyelids. Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Bilateral tonic-clonic seizure with generalized onset (HP:0025190): A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure. Evidence: PCS. Frequency: 4/4. (PMID:36214804)
- Typical absence seizure (HP:0011147): A typical absence seizure is a type of generalized non-motor (absence) seizure characterized by its sudden onset, interruption of ongoing activities, a blank stare, possibly a brief upward deviation of the eyes. Usually the patient will be unresponsive when spoken to. Duration is a few seconds to half a minute with very rapid recovery. Although not always available, an EEG would usually show 3 Hz generalized epileptiform discharges during the event. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Anomalous pulmonary venous return (HP:0010772): A developmental defect characterized by abnormal connection of one or more pulmonary veins to the superior or inferior vena cava, the right atrium, or the coronary sinus, resulting in a left-to-right shunt of oxygenated blood. Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Muscular ventricular septal defect (HP:0011623): The trabecular septum is the largest part of the interventricular septum. It extends from the membranous septum to the apex and superiorly to the infundibular septum. A defect in the trabecular septum is called muscular VSD if the defect is completely rimmed by muscle. Evidence: PCS. Frequency: 1/14. (PMID:36214804)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 5/14. (PMID:36214804)
- Non-convulsive status epilepticus without coma (HP:0032671): A type of status epilepticus without prominent motor symptoms in the absence of coma. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- 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: 3/3. (PMID:36214804)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: PCS. Frequency: 1/1. (PMID:36214804)
- Aortic tortuosity (HP:0006687): Abnormal tortuous (i.e., twisted) form of the aorta. Evidence: PCS. Frequency: 0/13. (PMID:36214804)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: PCS. Frequency: 1/1. (PMID:38513146)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 5/14. (PMID:36214804)
These phenotypes are associated with the disease neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities (OMIM:621390).