- Echolalia (HP:0010529): Echolalia is the automatic imitative repetition of sounds, words, or phrases in the absence of explicit awareness. The repeated words or phrases are typically odd or used in a non-social manner. These can be words or phrases that the affected individual has heard or invented. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- 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: 14/44. (PMID:34415117;PMID:30631761;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:31721432;PMID:38441608;PMID:24998929)
- 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: 14/43. (PMID:34415117;PMID:30631761;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:24998929;PMID:38441608;PMID:31721432)
- Pyloric stenosis (HP:0002021): Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss. Evidence: PCS. Frequency: 1/10. (PMID:31721432)
- 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: 7/17. (PMID:30631761;PMID:31001818;PMID:31980904;PMID:24998929;PMID:32309624)
- 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: 1/43. (PMID:30631761;PMID:34415117;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:24998929;PMID:31721432;PMID:38441608)
- 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: 9/39. (PMID:34415117;PMID:31001818;PMID:31980904;PMID:26789910;PMID:24998929;PMID:31721432)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/12. (PMID:30631761;PMID:34415117;PMID:31980904;PMID:26789910;PMID:38441608;PMID:32309624)
- Pica (HP:0011856): An appetite for and the persistent ingestion of non-food substances such as clay. In order to diagnose pica, this behavior must have persisted over a period of at least one month. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- Abdominal distention (HP:0003270): Distention of the abdomen. Evidence: PCS. Frequency: 1/16. (PMID:31980904;PMID:24998929)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 4/12. (PMID:31980904;PMID:24998929)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: PCS. Frequency: 2/24. (PMID:31001818;PMID:24998929)
- 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: 1/10. (PMID:31721432)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/3. (PMID:34415117;PMID:27595554)
- 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: 1/1. (PMID:32309624)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/3. (PMID:38441608)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 33/43. (PMID:34415117;PMID:31001818;PMID:31980904;PMID:26789910;PMID:24998929;PMID:31721432;PMID:38441608)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 3/4. (PMID:31980904)
- 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: 11/18. (PMID:34415117;PMID:31980904;PMID:24998929;PMID:38441608)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 2/4. (PMID:34415117;PMID:38441608)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 12/28. (PMID:31001818;PMID:27595554;PMID:31980904;PMID:24998929)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 4/19. (PMID:24998929;PMID:31721432)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/10. (PMID:31721432)
- 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: 3/3. (PMID:24998929;PMID:31721432;PMID:32309624)
- 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: 1/1. (PMID:26789910)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 8/15. (PMID:34415117;PMID:24998929;PMID:38441608;PMID:32309624)
- Inflammation of the large intestine (HP:0002037): Inflammation, or an inflammatory state in the large intestine. Evidence: PCS. Frequency: 1/16. (PMID:31980904;PMID:24998929)
- Tall stature (HP:0000098): A height above that which is expected according to age and gender norms. Evidence: PCS. Frequency: 22/38. (PMID:30631761;PMID:31001818;PMID:31980904;PMID:24998929;PMID:31721432;PMID:38441608)
- Writer's cramp (HP:0002356): A focal dystonia of the fingers, hand, and/or forearm that appears when the affected person attempts to do a task that requires fine motor movements such as writing or playing a musical instrument. Evidence: PCS. Frequency: 2/4. (PMID:34415117;PMID:38441608)
- 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: 1/2. (PMID:34415117;PMID:38441608)
- 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: 1/1. (PMID:26789910)
- Macroorchidism (HP:0000053): The presence of abnormally large testes. Evidence: PCS. Frequency: 2/3. (PMID:31980904)
- Striae distensae (HP:0001065): Thinned, erythematous, depressed bands of atrophic skin. Initially, striae appear as flattened and thinned, pinkish linear regions of the skin. Striae tend to enlarge in length and become reddish or purplish. Later, striae tend to appear as white, depressed bands that are parallel to the lines of skin tension. Striae distensae occur most often in areas that have been subject to distension such as the lower back, buttocks, thighs, breast, abdomen, and shoulders. Evidence: PCS. Frequency: 1/10. (PMID:31721432)
- Cerebral palsy (HP:0100021): Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems. Evidence: PCS. Frequency: 1/16. (PMID:24998929;PMID:32309624)
- Sleep onset insomnia (HP:0031354): Difficulty initiating sleep, that is, increased sleep onset latency, refers to the condition where it takes 30 minutes or more to fall asleep. Evidence: PCS. Frequency: 11/24. (PMID:31001818;PMID:27595554;PMID:24998929)
- Late chronotype (HP:0031874): A tendency towards waking up very late in the morning and staying up late at night. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- Reduced production of gestures (HP:4000081): Diminished use of typical non-verbal conversational gestures such as shaking the head to indicate no or nodding the head to indicate yes. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- 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: 1/1. (PMID:26789910)
- Hyperbilirubinemia (HP:0002904): An increased amount of bilirubin in the blood. Evidence: PCS. Frequency: 3/10. (PMID:31001818)
- Heterotropia (HP:0032012): Manifest deviation of the visual axes not controlled by fusion. Evidence: PCS. Frequency: 2/12. (PMID:31001818;PMID:31980904)
- 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: 1/10. (PMID:31721432)
- 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: 1/10. (PMID:31721432)
- 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: 5/14. (PMID:31980904;PMID:31721432)
- 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:24998929)
- Wide nose (HP:0000445): Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae. Evidence: PCS. Frequency: 15/15. (PMID:31980904;PMID:24998929;PMID:32309624)
- Borderline intellectual disability (HP:0006889): Borderline intellectual disability is defined as an intelligence quotient (IQ) in the range of 70-85. Evidence: PCS. Frequency: 5/37. (PMID:30631761;PMID:34415117;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:38441608;PMID:24998929)
- Stereotypic upper-extremity movements (HP:5200018): Abnormal movements of the upper extremities. Evidence: PCS. Frequency: 1/1. (PMID:31980904)
- 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: 1/1. (PMID:26789910)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 6/6. (PMID:31980904;PMID:24998929)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 15/18. (PMID:34415117;PMID:31001818;PMID:31980904;PMID:26789910;PMID:32309624)
- Pronoun reversal (HP:4000073): Atypical language features characterized by first vs. second or third person pronoun errors such as using 'you' or 'he/she' in place of 'I'. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- 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: 1/15. (PMID:24998929)
- 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: 6/43. (PMID:30631761;PMID:34415117;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:38441608;PMID:31721432;PMID:24998929)
- 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: 11/30. (PMID:31001818;PMID:31980904;PMID:26789910;PMID:24998929;PMID:38441608)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: PCS. Frequency: 4/4. (PMID:31980904)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: PCS. Frequency: 6/6. (PMID:30631761;PMID:24998929)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 4/16. (PMID:34415117;PMID:31001818;PMID:31980904;PMID:38441608)
- Stereotypical hand wringing (HP:0012171): Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement. Evidence: PCS. Frequency: 4/5. (PMID:31980904;PMID:26789910)
- 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: 33/46. (PMID:34415117;PMID:30631761;PMID:31001818;PMID:31980904;PMID:26789910;PMID:24998929;PMID:31721432;PMID:38441608;PMID:32309624)
- Prominent supraorbital ridges (HP:0000336): Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones. Evidence: PCS. Frequency: 29/40. (PMID:34415117;PMID:31001818;PMID:31980904;PMID:24998929;PMID:31721432;PMID:38441608;PMID:32309624)
- Cerebellar vermis atrophy (HP:0006855): Wasting (atrophy) of the vermis of cerebellum. Evidence: PCS. Frequency: 2/5. (PMID:34415117;PMID:38441608)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 4/17. (PMID:27595554;PMID:31980904;PMID:24998929)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 2/10. (PMID:31721432)
- Typically de novo (HP:0025352): Description of conditions that are exclusively or predominantly observed to display de novo variants. In some cases, this may be due to the limited reproductive fitness of affected individuals. Evidence: PCS. (PMID:24998929)
- 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: 15/17. (PMID:30631761;PMID:31001818;PMID:27595554;PMID:31980904;PMID:26789910;PMID:32309624)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 10/20. (PMID:31980904;PMID:26789910;PMID:24998929)
- 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: 1/15. (PMID:24998929)
- Open mouth (HP:0000194): A facial appearance characterized by a permanently or nearly permanently opened mouth. Evidence: PCS. Frequency: 1/1. (PMID:26789910)
- 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: 4/5. (PMID:34415117;PMID:38441608)
- Tall chin (HP:0400000): Increased vertical distance from the vermillion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 3/7. (PMID:34415117;PMID:31980904;PMID:32309624)
- Psychosis (HP:0000709): A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis. Evidence: PCS. Frequency: 3/26. (PMID:27595554;PMID:24998929;PMID:31721432)
- Reduced social responsiveness (HP:0012760): A reduced ability to participate in the back-and-forth flow of social interaction appropriate to culture and developmental level, which is normally characterized by an influence of the behavior of one person on the behavior of another person. This results in difficulty interacting with others through emotional, physical, or verbal communication. Evidence: PCS. Frequency: 3/10. (PMID:31001818;PMID:31721432)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 1/10. (PMID:31721432)
- 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: 1/1. (PMID:26789910)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 2/10. (PMID:31001818)
- Overweight (HP:0025502): Increased body weight with a body mass index of 25-29.9 kg per square meter. Evidence: PCS. Frequency: 3/20. (PMID:30631761;PMID:31980904;PMID:24998929;PMID:38441608)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 11/11. (PMID:26789910;PMID:24998929)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: PCS. Frequency: 5/11. (PMID:31001818;PMID:31980904)
- 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: 7/33. (PMID:31001818;PMID:31721432;PMID:24998929)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 1/6. (PMID:34415117;PMID:38441608;PMID:32309624)
These phenotypes are associated with the disease intellectual developmental disorder with autism and macrocephaly (OMIM:615032).