- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Hip dislocation (HP:0002827): Displacement of the femur from its normal location in the hip joint. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Cyclopia (HP:0009914): Cyclopia is a congenital abnormality in which there is only one eye. That eye is centrally placed in the area normally occupied by the root of the nose. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Single naris (HP:0009932): The presence of only a single nostril. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Central hypothyroidism (HP:0011787): A type of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland. Central hypothyroidism is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormal gastrointestinal tract morphology (HP:0012718): Abnormal structure of the gastrointestinal tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Proboscis (HP:0012806): A fleshy, tube-like structure usually located in the midline of the face or just to one side of the midline. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormal heart rate variability (HP:0031860): Any abnormality in the variability of the time interval between successive heartbeats. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormality of limbs (HP:0040064). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:93925)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:93925)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:93925)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:93925)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:93925)
- 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: Very frequent (HP:0040281). (ORPHA:93925)
- 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:93925)
- Median cleft upper lip (HP:0000161): A type of cleft lip presenting as a midline (median) gap in the upper lip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Depressed nasal ridge (HP:0000457): Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: Frequent (HP:0040282). (ORPHA:93925)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: Frequent (HP:0040282). (ORPHA:93925)
- 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:93925)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: Frequent (HP:0040282). (ORPHA:93925)
- Abnormality of the autonomic nervous system (HP:0002270): An abnormality of the autonomic nervous system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormal brainstem morphology (HP:0002363): An anomaly of the brainstem. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Limb dystonia (HP:0002451): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormal pattern of respiration (HP:0002793): An anomaly of the rhythm or depth of breathing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Central apnea (HP:0002871): Apnea resulting from depression of the respiratory centers in the medulla oblongata. There is a lack of respiratory effort rather than obstruction of airflow. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Temperature instability (HP:0005968): Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Chronic lung disease (HP:0006528): According to the definitions of the American and British Thoracic Societies, including pulmonary functional tests, X-rays, and CT scans for items such as fibrosis, bronchiectasis, bullae, emphysema, nodular or lymphomatous abnormalities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Sleep-wake cycle disturbance (HP:0006979): Any abnormality of an individual's circadian rhythm that affects the timing of sleeping and being awake is referred to as a sleep-wake disorder. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Oromotor apraxia (HP:0007301): Oral-motor apraxia is the inability to volitionally sequence oral movements of the speech structure for nonspeech tasks in the absence of neuromuscular deficits such as paralysis or muscle weakness. Oral-motor apraxia is diagnosed when, despite intact sensory motor function an individual is unable to use these effector systems under voluntary control. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Floppy infant (HP:0008947): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Aplasia of the falx cerebri (HP:0010654): A developmental defect characterized by aplasia of the Falx cerebri. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormal central motor function (HP:0011442): An anomaly of the control or production of movement in the central nervous system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormal hypothalamus physiology (HP:0012285): An abnormal functionality of the hypothalamus. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormal morphology of the olfactory bulb (HP:0040327): An abnormal morphology of the olfactory bulb (bulbus olfactorius), which is involved in olfaction, i.e. the sense of smell. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Neural tube defect (HP:0045005): A neural tube defect arises when the neural tube, the embryonic precursor of the brain and spinal cord, fails to close during neurulation. The cranial region (anencephaly) or the low spine (open spina bifida; myelomeningocele) are most commonly affected although, in the severe NTD craniorachischisis, almost the entire neural tube remains open, from midbrain to low spine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:93925)
- Abnormality of the genitourinary system (HP:0000119): The presence of any abnormality of the genitourinary system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormality of the endocrine system (HP:0000818): An abnormality of the endocrine system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- 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: Occasional (HP:0040283). (ORPHA:93925)
- Panhypopituitarism (HP:0000871): A pituitary functional deficit affecting all the anterior pituitary hormones (growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and prolactin). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Diabetes insipidus (HP:0000873): A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- Abnormality of the skeletal system (HP:0000924): An abnormality of the skeletal system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:93925)
These phenotypes are associated with the disease Alobar holoprosencephaly (ORPHA:93925).