- 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: 2/9. Onset: Childhood onset (HP:0011463). (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- Congenital hip dislocation (HP:0001374). Evidence: PCS. Frequency: 1/9. Onset: Congenital onset (HP:0003577). (PMID:34186028)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 5/9. (PMID:34186028)
- Exaggerated cupid's bow (HP:0002263): More pronounced paramedian peaks and median notch of the Cupid's bow. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 7/9. (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- Elongated superior cerebellar peduncle (HP:0011933): Increased length of the superior cerebellar peduncle. Evidence: PCS. Frequency: 1/10. (PMID:34186028)
- 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: 2/9. (PMID:34186028)
- Hypoplasia of the pons (HP:0012110): Underdevelopment of the pons. Evidence: PCS. Frequency: 3/9. (PMID:34186028)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- 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: 2/9. (PMID:34186028)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Long fingers (HP:0100807): The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 7/7. (PMID:34186028)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Retinal dystrophy (HP:0000556): 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: 1/9. (PMID:34186028)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 3/9. (PMID:34186028)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 3/8. (PMID:34186028)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 8/9. (PMID:34186028)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- 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: 8/8. (PMID:34186028)
- Low anterior hairline (HP:0000294): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 8/8. (PMID:34186028)
- 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: 2/9. (PMID:34186028)
- Dislocated radial head (HP:0003083): A dislocation of the head of the radius from its socket in the elbow joint. Evidence: PCS. Frequency: 1/11. Onset: Congenital onset (HP:0003577). (PMID:34186028)
- High anterior hairline (HP:0009890): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 1/8. (PMID:34186028)
- 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: 3/7. (PMID:34186028)
- Hypotelorism (HP:0000601): Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Partial agenesis of the corpus callosum (HP:0001338): A partial failure of the development of the corpus callosum. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Almond-shaped palpebral fissure (HP:0007874): A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- Hypoplastic coccygeal vertebrae (HP:0008447). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Short philtrum (HP:0000322): Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- 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:34186028)
- 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: 1/9. (PMID:34186028)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Bilateral talipes equinovarus (HP:0001776): Bilateral clubfoot deformity. Evidence: PCS. Frequency: 1/11. (PMID:34186028)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Fetal pyelectasis (HP:0010945): Mild pyelectasis is defined as a hypoechoic spherical or elliptical space within the renal pelvis that measures at least 5mm and not more than 10 mm. The measurement is taken on a transverse section through the fetal renal pelvis using the maximum anterior-to-posterior measurement. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: PCS. Frequency: 8/8. (PMID:34186028)
- Anisometropia (HP:0012803): Inequality of refractive power of the two eyes. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Frequent temper tantrums (HP:0025161): Temper tantrums that occur more frequently compared to the temper tantrums that are a part of the normal developmental process. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/9. (PMID:34186028)
- Narrow nasal ridge (HP:0000418): Decreased width of the nasal ridge. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: PCS. Frequency: 3/9. (PMID:34186028)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- 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: 1/9. (PMID:34186028)
- 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: 2/9. (PMID:34186028)
- Low hanging columella (HP:0009765): Columella extending inferior to the level of the nasal base, when viewed from the side. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Aqueductal stenosis (HP:0002410): Stenosis of the cerebral aqueduct (also known as the mesencephalic duct, aqueductus mesencephali, or aqueduct of Sylvius), which connects the third cerebral ventricle in the diencephalon to the fourth ventricle, which is between the pons and cerebellum. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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:34186028)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Prominent metopic ridge (HP:0005487): Vertical bony ridge positioned in the midline of the forehead. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Abnormal dentate nucleus morphology (HP:0100321): An abnormality of the dentate nucleus. Evidence: PCS. Frequency: 3/9. (PMID:34186028)
- Dilation of Virchow-Robin spaces (HP:0012520): Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 2/9. (PMID:34186028)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: PCS. Frequency: 3/9. (PMID:34186028)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- 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: 1/9. Onset: Congenital onset (HP:0003577). (PMID:34186028)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 1/3. (PMID:34186028)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 1/9. (PMID:34186028)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 2/9. (PMID:34186028)
These phenotypes are associated with the disease neurodevelopmental disorder with hypotonia and brain abnormalities (OMIM:619512).