- 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: 3/9. (PMID:33280099)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- 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: 1/1. (PMID:30160831)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 2/9. (PMID:33280099)
- 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:30160831)
- Gait ataxia (HP:0002066): 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: 1/9. (PMID:33280099)
- Protruding tongue (HP:0010808): Tongue extending beyond the alveolar ridges or teeth at rest. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- 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: 1/1. (PMID:30160831)
- 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: 1/1. (PMID:30160831)
- 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: 1/9. (PMID:33280099)
- Short palpebral fissure (HP:0012745): Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- 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: 2/10. (PMID:30160831;PMID:33280099)
- Appendicular hypotonia (HP:0012389): Muscular hypotonia of one or more limbs. Evidence: PCS. Frequency: 3/9. (PMID:33280099)
- 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: 1/9. (PMID:33280099)
- 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: 3/9. (PMID:33280099)
- Hypoplastic fingernail (HP:0001804): Underdevelopment of a fingernail. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 9/9. (PMID:33280099)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Microdontia (HP:0000691): Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- 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: 10/10. (PMID:30160831;PMID:33280099)
- Chorea (HP:0002072): Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Thoracolumbar kyphosis (HP:0005619): Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Bilateral camptodactyly (HP:0005617). Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 4/9. (PMID:33280099)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Elbow flexion contracture (HP:0002987): An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Focal-onset seizure (HP:0007359): 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: 1/9. (PMID:33280099)
- 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:30160831)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 4/10. (PMID:30160831;PMID:33280099)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Acral blistering (HP:0031045): Bullae (defined as fluid-filled blisters more than 5 mm in diameter with thin walls) of the skin with an acral distribution (affecting peripheral regions such as hands and feet). Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Enamel hypoplasia (HP:0006297): Developmental hypoplasia of the dental enamel. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- 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: 1/1. (PMID:30160831)
- 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: 2/9. (PMID:33280099)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Aspiration (HP:0002835): Inspiration of a foreign object into the airway. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Pachygyria (HP:0001302): Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: PCS. Frequency: 1/9. (PMID:33280099)
- Gingival overgrowth (HP:0000212): Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Hemangioma (HP:0001028): A hemangioma is a benign tumor characterized by blood-filled spaces lined by benign endothelial cells. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma (in contrast to a hemangioma with small endothelial spaces, which is called capillary hemangioma). Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 5/9. (PMID:33280099)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 4/10. (PMID:30160831;PMID:33280099)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 3/9. (PMID:33280099)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 5/9. (PMID:33280099)
- 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: 2/9. (PMID:33280099)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 3/10. (PMID:30160831;PMID:33280099)
- EEG with photoparoxysmal response (HP:0010852): EEG abnormalities (epileptiform discharges) evoked by flashing lights or black and white striped patterns. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- 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:30160831)
- Central sleep apnea (HP:0010536): Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Myoclonic status epilepticus (HP:0032667): 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: 1/9. (PMID:33280099)
- 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: 4/9. (PMID:33280099)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Abnormal conjugate eye movement (HP:0000549): Any deviation from the normal motor coordination of the eyes that allows for bilateral fixation on a single object. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 2/9. (PMID:33280099)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/1. (PMID:30160831)
- Polymicrogyria (HP:0002126): Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds). Evidence: PCS. Frequency: 1/9. (PMID:33280099)
These phenotypes are associated with the disease developmental and epileptic encephalopathy 100 (OMIM:619777).