- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- Brain imaging abnormality (HP:0410263): An anomaly of metabolism or structure of the brain identified by imaging. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:268261)
- Abnormality of the genitourinary system (HP:0000119): The presence of any abnormality of the genitourinary system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Failure to thrive in infancy (HP:0001531). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Abnormal foot morphology (HP:0001760): An abnormality of the skeleton of foot. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Abnormal toe morphology (HP:0001780): An anomaly of a toe. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Broad-based gait (HP:0002136): An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Hypoplasia of the brainstem (HP:0002365): Underdevelopment of the brainstem. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- CNS hypomyelination (HP:0003429): Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- 2-4 toe cutaneous syndactyly (HP:0005768): A soft tissue continuity in the anteroposterior axis between the toes 2, 3, and 4. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Posterior pituitary hypoplasia (HP:0011757): Underdevelopment of the neurohypophysis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:268261)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Chordee (HP:0000041): A congenital anomaly of the penis characterized by ventral (i.e., downward), lateral, or ventrolateral curvature of the shaft and glans penis of more than 30 degrees. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Shawl scrotum (HP:0000049): Superior margin of the scrotum superior to the base of the penis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Unilateral renal agenesis (HP:0000122): A unilateral form of agenesis of the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Abnormality of the endocrine system (HP:0000818): An abnormality of the endocrine system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Hallux valgus (HP:0001822): Lateral deviation of the great toe (i.e., in the direction of the little toe). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Generalized myoclonic seizure (HP:0002123): A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Atonic seizure (HP:0010819): Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Dilatation of the renal pelvis (HP:0010946): The presence of dilatation of the renal pelvis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Nasogastric tube feeding in infancy (HP:0011470): Feeding problem necessitating nasogastric tube feeding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Broad chin (HP:0011822): Increased width of the midpoint of the mandible (mental protuberance) and overlying soft tissue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Short 5th toe (HP:0011917): Underdevelopment (hypoplasia) of the fifth toe. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Abnormal optic chiasm morphology (HP:0025163): A structural abnormality of the optic chiasm.The optic chiasm, located below the hypothalamus, is a partial crossing of the optic nerves. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:268261)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Cleft soft palate (HP:0000185): Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Astigmatism (HP:0000483): A type of refraction error associated with abnormal curvatures on the anterior and/or posterior surface of the cornea. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Retinal detachment (HP:0000541): Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Iris coloboma (HP:0000612): A coloboma of the iris. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Decreased response to growth hormone stimulation test (HP:0000824): Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Abnormal pulmonary valve morphology (HP:0001641): Any structural abnormality of the pulmonary valve. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Aortic valve stenosis (HP:0001650): The presence of a stenosis (narrowing) of the aortic valve. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Aortic regurgitation (HP:0001659): An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Premature thelarche (HP:0010314): Premature development of the breasts. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Polydactyly (HP:0010442): A congenital anomaly characterized by the presence of supernumerary fingers or toes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Supernumerary tooth (HP:0011069): The presence of one or more teeth additional to the normal number. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Osteochondrosis (HP:0040188): Abnormal growth ossification centers in children. Initially a degeneration/ necrosis followed by regeneration or recalcification. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
- Breast aplasia (HP:0100783): Failure to develop and congenital absence of the breast. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:268261)
These phenotypes are associated with the disease DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion (ORPHA:268261).