- 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: 10/17. (PMID:39038237;PMID:38977784;PMID:39708122)
- 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: 4/16. (PMID:38977784;PMID:39708122)
- 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: 2/9. (PMID:38977784)
- 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: 2/2. (PMID:38977784)
- 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: 0/5. (PMID:39708122)
- 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: 3/11. (PMID:38977784;PMID:39708122)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/6. (PMID:39038237;PMID:39708122)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 2/2. (PMID:39038237;PMID:39708122)
- Cleft lip (HP:0410030): A gap in the lip or lips. Evidence: PCS. Frequency: 0/5. (PMID:39708122)
- Delayed ability to crawl (HP:0033128): A failure to achieve the ability to crawl at an appropriate developmental stage. Normal infant motor development is marked by a series of postural milestones including learning to crawl on hands and knees between the ages of 6 and 10 months. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- Cafe-au-lait spot (HP:0000957): Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children. Evidence: PCS. Frequency: 1/1. (PMID:38977784)
- 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: 6/15. (PMID:38977784;PMID:39708122)
- Thick vermilion border (HP:0012471): Increased width of the skin of vermilion border region of upper lip. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- 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: 2/10. (PMID:38977784)
- Long palpebral fissure (HP:0000637): Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures. Evidence: PCS. Frequency: 2/5. (PMID:38977784;PMID:39708122)
- 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: 3/8. (PMID:38977784;PMID:39708122)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 2/2. (PMID:38977784)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- Large earlobe (HP:0009748): Increased volume of the earlobe, that is, abnormally prominent ear lobules. Evidence: PCS. Frequency: 1/10. (PMID:38977784)
- Solitary median maxillary central incisor (HP:0006315): A single maxillary central incisor positioned in the midline with morphological symmetry of the crown and bordered by lateral incisors. Evidence: PCS. Frequency: 0/5. (PMID:39708122)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/1. (PMID:39038237)
- 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: 1/1. (PMID:39708122)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 9/15. (PMID:38977784;PMID:39708122)
- Cleft palate (HP:0000175): Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Evidence: PCS. Frequency: 0/5. (PMID:39708122)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/3. (PMID:39708122)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- 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: 14/14. (PMID:39038237;PMID:38977784;PMID:39708122)
- Abnormal CNS myelination (HP:0011400): An abnormality of myelination of nerves in the central nervous system. Evidence: PCS. Frequency: 0/1. (PMID:39038237)
- Abnormality of movement (HP:0100022): An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements. Evidence: PCS. Frequency: 0/5. (PMID:38977784)
- 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: 2/10. (PMID:38977784)
- Prominent nose (HP:0000448): Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip. Evidence: PCS. Frequency: 4/4. (PMID:39708122)
- Microphthalmia (HP:0000568): A developmental anomaly characterized by abnormal smallness of one or both eyes. Evidence: PCS. Frequency: 1/1. (PMID:39038237)
- Autosomal recessive inheritance (HP:0000007): 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:38977784)
- 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: 1/1. (PMID:39038237)
- 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: 1/1. (PMID:39708122)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 10/12. (PMID:39708122;PMID:38977784)
- 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: 1/10. (PMID:38977784)
- 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: 1/1. (PMID:39038237)
- Tics (HP:0100033): Repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Evidence: PCS. Frequency: 1/1. (PMID:39038237)
- 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: 3/11. (PMID:38977784)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 1/9. (PMID:38977784)
- Hyperplasia of midface (HP:0012371): Abnormally anterior positioning of the infraorbital and perialar regions, or increased convexity of the face, or increased nasolabial angle. The midface includes the maxilla, the cheeks, the zygomas, and the infraorbital and perialar regions of the face. Evidence: PCS. Frequency: 3/3. (PMID:39708122)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- 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: 1/1. (PMID:39038237)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 1/1. (PMID:39038237)
- 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:39038237)
- Protruding ear (HP:0000411): Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective). Evidence: PCS. Frequency: 6/16. (PMID:39038237;PMID:38977784;PMID:39708122)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 1/3. (PMID:38977784)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: PCS. Frequency: 1/1. (PMID:39708122)
- 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:39708122)
- Abnormal skin pigmentation (HP:0001000): An abnormality of the pigmentation of the skin. Evidence: PCS. Frequency: 0/7. (PMID:38977784)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/7. (PMID:38977784)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 2/2. (PMID:39038237;PMID:39708122)
- 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: 10/13. (PMID:39038237;PMID:38977784;PMID:39708122)
- Short palm (HP:0004279): Short palm. Evidence: PCS. Frequency: 1/4. (PMID:38977784)
- 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: 5/6. (PMID:38977784)
- Ectopic testis (HP:6000460): Localization of the testis in an anatomic location other than the scrotum. Evidence: PCS. Frequency: 1/1. (PMID:38977784)
- 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: 1/1. (PMID:39038237)
- Limb dystonia (HP:0002451): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: PCS. Frequency: 1/1. (PMID:38977784)
- Reduced social smiling (HP:5200102): Reduced production of smiles during engagement with an interactive parent, caregiver, or peer. Evidence: PCS. Frequency: 3/4. (PMID:39708122)
- Poor sleep (HP:4000064): Subjectively or observationally reported sleep that is insufficiently restorative, disrupted, or of inadequate quality, regardless of duration. Poor sleep may involve difficulty maintaining sleep continuity, frequent awakenings, a sense of light or shallow sleep, or waking up feeling unrefreshed. It is typically identified through self-report or clinical interview and not by objective measurements. Evidence: PCS. Frequency: 1/1. (PMID:39038237)
- Low frustration tolerance (HP:0000744): The feeling of frustration can be defined as an emotional reaction that occurs when a desired goal is not achieved. Frustration intolerance is defined as an age-inappropriate response to frustration, characterized by crying or temper tantrums in children, or aggressive or other maladaptive behaviors. Evidence: PCS. Frequency: 1/10. (PMID:38977784)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/4. (PMID:38977784)
- 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: 6/8. (PMID:38977784;PMID:39708122)
These phenotypes are associated with the disease neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities (OMIM:621182).