- 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: 4/9. (PMID:38753057)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 2/2. (PMID:38753057)
- 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: 3/3. (PMID:38753057)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- 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: 4/6. (PMID:38753057)
- 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: 2/9. (PMID:38753057)
- Profound intellectual disability (HP:0002187): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: PCS. Frequency: 2/2. (PMID:38753057)
- 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: 4/9. (PMID:38753057)
- 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:38753057)
- Short nose (HP:0003196): Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 2/2. (PMID:38753057)
- Ataxia (HP:0001251): 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: 2/2. (PMID:38753057)
- Gait imbalance (HP:0002141). Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Broad hallux (HP:0010055): Visible increase in width of the hallux without an increase in the dorso-ventral dimension. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 2/9. (PMID:38753057)
- Overlapping toe (HP:0001845): Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- 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: 3/9. (PMID:38753057)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- 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: 2/2. (PMID:38753057)
- Dental crowding (HP:0000678): Changes in alignment of teeth in the dental arch. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/3. (PMID:38753057)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 4/9. (PMID:38753057)
- 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: 1/2. (PMID:38753057)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 3/9. (PMID:38753057)
- Hooded eyelid (HP:0030820): Eyelid partly covered by skin when eyes are open. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- 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:38753057)
- Expressive language delay (HP:0002474): A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts. Evidence: PCS. Frequency: 2/2. (PMID:38753057)
- Ascending tubular aorta aneurysm (HP:0004970): An abnormal localized widening (dilatation) of the tubular part of the ascending aorta. Evidence: PCS. Frequency: 0/8. (PMID:38753057)
- 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: 1/1. (PMID:38753057)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 7/8. (PMID:38753057)
- 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: 1/1. (PMID:38753057)
- 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: 1/9. (PMID:38753057)
- Wide nasal base (HP:0012810): Increased distance between the attachments of the alae nasi to the face. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- 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: 1/1. (PMID:38753057)
- Amblyopia (HP:0000646): Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways. Evidence: PCS. Frequency: 1/6. (PMID:38753057)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- 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:38753057)
- 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: 6/9. (PMID:38753057)
- 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:38753057)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 1/9. (PMID:38753057)
- 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: 2/9. (PMID:38753057)
- Narrow palate (HP:0000189): Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective). Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 2/9. (PMID:38753057)
- Medial flaring of the eyebrow (HP:0010747): An abnormal distribution of eyebrow hair growth in the medial direction. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 1/6. (PMID:38753057)
- Blepharophimosis (HP:0000581): A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. Evidence: PCS. Frequency: 2/9. (PMID:38753057)
- Prominent nasal tip (HP:0005274). Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 1/2. (PMID:38753057)
- Flat face (HP:0012368): Absence of concavity or convexity of the face when viewed in profile. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Pain insensitivity (HP:0007021): Inability to perceive painful stimuli. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- 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: 1/1. (PMID:38753057)
- Periventricular leukomalacia (HP:0006970): Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Evidence: PCS. Frequency: 2/7. (PMID:38753057)
- 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: 2/9. (PMID:38753057)
- Downturned corners of mouth (HP:0002714): A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure. Evidence: PCS. Frequency: 3/9. (PMID:38753057)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Cerebellar vermis atrophy (HP:0006855): Wasting (atrophy) of the vermis of cerebellum. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- 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: 6/7. (PMID:38753057)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 2/4. (PMID:38753057)
- Everted lower lip vermilion (HP:0000232): An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- 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: 7/7. (PMID:38753057)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Narrow palpebral fissure (HP:0045025): Reduction in the vertical distance between the upper and lower eyelids. Evidence: PCS. Frequency: 1/9. (PMID:38753057)
- Severe global developmental delay (HP:0011344): 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:38753057)
- Lateral ventricular asymmetry (HP:0100960): Abnormal difference in size between the left and right lateral cerebral ventricles. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. Frequency: 2/8. (PMID:38753057)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 0/9. (PMID:38753057)
- Chilblains (HP:0009710): Chilblains, also called perniosis, are an inflammatory skin condition related to an abnormal vascular response to the cold. We are unaware of a reliable estimate of incidence. It typically presents as tender, pruritic red or bluish lesions located symmetrically on the dorsal aspect of the fingers, toes, ears and nose. Less commonly, reports describe involvement of the thighs and buttocks. The lesions present hours after exposure to cold and usually resolve spontaneously in one to three weeks. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: PCS. Frequency: 1/2. (PMID:38753057)
- Oval face (HP:0000300): A face with a rounded and slightly elongated outline. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Epistaxis (HP:0000421): Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose. Evidence: PCS. Frequency: 1/1. (PMID:38753057)
- Mitral valve prolapse (HP:0001634): One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle. Evidence: PCS. Frequency: 1/8. (PMID:38753057)
These phenotypes are associated with the disease Harel-Tora neurodevelopmental syndrome (OMIM:621377).