- Decreased body weight (HP:0004325): Abnormally low body weight. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Bitemporal hollowing (HP:0025386): Depression of profile in both temporal regions. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 5/25. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Abnormality of the integument (HP:0001574): An abnormality of the integument, which consists of the skin and the superficial fascia. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 2/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Multifocal epileptiform discharges (HP:0010841): An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Thick vermilion border (HP:0012471): Increased width of the skin of vermilion border region of upper lip. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Hoarse voice (HP:0001609): Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Ankyloglossia (HP:0010296): Short or anteriorly attached lingual frenulum, associated with limited mobility of the tongue. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormal placenta morphology (HP:0100767): An abnormality of the placenta, the organ that connects the developing fetus to the uterine wall to enable nutrient uptake, waste elimination, and gas exchange. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- Isometric tremor (HP:0030185): An isometric tremor occurs with muscle contraction against a rigid stationary object (e.g., when making a fist). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: 2/29. (PMID:34211179)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Leukodystrophy (HP:0002415): Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Melanocytic nevus (HP:0000995): A oval and round, colored (usually medium-to dark brown, reddish brown, or flesh colored) lesion. Typically, a melanocytic nevus is less than 6 mm in diameter, but may be much smaller or larger. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Bruxism (HP:0003763): Bruxism is characterized by the grinding of the teeth including the clenching of the jaw and typically occur during sleep. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Neurofibroma (HP:0001067): A benign peripheral nerve sheath tumor that generally appears as a soft, skin-colored papule or small subcutaneous nodule. Individuals with neurofibromatosis can have numerous neurofibromas. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/21. (PMID:34211179)
- Nevus (HP:0003764): A nevus is a type of hamartoma that is a circumscribed stable malformation of the skin. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 4/29. (PMID:34211179)
- Breast mass (HP:0032408): A breast lump is any discrete mass in a breast noticed by the patient, significant other, or physician. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Gynecomastia (HP:0000771): Abnormal development of large mammary glands in males resulting in breast enlargement. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Abnormal curvature of the vertebral column (HP:0010674): The presence of an abnormal curvature of the vertebral column. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Nocturnal seizures (HP:0031951): Seizures that occur while the affected individual is sleeping. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 2/29. (PMID:34211179)
- Palpebral edema (HP:0100540): Edema in the region of the eyelids. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Peripheral demyelination (HP:0011096): A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormality of the skeletal system (HP:0000924): An abnormality of the skeletal system. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Violent behavior (HP:0008760): Conduct and/or behavior, both verbal and non-verbal, including but not limited to verbal and/or physical aggression, attacks, threats, harassment, intimidation, and other disruptive behaviors in any form or through any medium, that cause or have the potential to cause a reasonable person to fear physical harm from any individual(s) or group(s) towards any person(s) or property. This is commonly defined as a violent act characterized by the use of physical force, anger, or sudden intense activity. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Repetitive compulsive behavior (HP:0008762). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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:34211179)
- Abdominal pain (HP:0002027): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 4/22. (PMID:34211179)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 7/22. (PMID:34211179)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 23/27. (PMID:34211179)
- Intention tremor (HP:0002080): A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Decreased CSF 5-methyltetrahydrofolate concentration (HP:0012446): A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Maternal hypertension (HP:0008071): Increased blood pressure during a pregnancy. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- 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: PCS. Frequency: 2/29. (PMID:34211179)
- 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: 3/20. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Clonic seizure (HP:0020221): A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Iris coloboma (HP:0000612): A coloboma of the iris. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Laryngeal cleft (HP:0008751): Presence of a gap in the posterior laryngotracheal wall with a continuity between the larynx and the esophagus. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Head titubation (HP:0002599): A head tremor of moderate speed (3 to 4 Hz) in the anterior-posterior direction. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Progressive spastic quadriplegia (HP:0002478). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Osteomyelitis (HP:0002754): Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Torticollis (HP:0000473): Involuntary contractions of the neck musculature resulting in an abnormal posture of or abnormal movements of the head. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Bursitis (HP:0025232): Inflammation of a synovial bursa. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 26/27. (PMID:34211179)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Bilateral sensorineural hearing impairment (HP:0008619): A form of sensorineural hearing impairment that affects both ears. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 3/25. (PMID:34211179)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- 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: 2/29. (PMID:34211179)
- Short uvula (HP:0010812): Decreased length of the uvula. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Broad eyebrow (HP:0011229): Regional increase in the width (height) of the eyebrow. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Impulsivity (HP:0100710): Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Food allergy (HP:0500093): Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormal abdomen morphology (HP:0001438): A structural abnormality of the abdomen ('belly'), that is, the part of the body between the pelvis and the thorax. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Overweight (HP:0025502): Increased body weight with a body mass index of 25-29.9 kg per square meter. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Falls (HP:0002527). Evidence: PCS. Frequency: 6/29. (PMID:34211179)
- 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: 12/22. (PMID:34211179)
- Dilatation of the cerebral artery (HP:0004944): The presence of a localized dilatation or ballooning of a cerebral artery. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Coloboma (HP:0000589): A developmental defect characterized by a cleft of some portion of the eye or ocular adnexa. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Aortic aneurysm (HP:0004942): Aortic dilatation refers to a dimension that is greater than the 95th percentile for the normal person age, sex and body size. In contrast, an aneurysm is defined as a localized dilation of the aorta that is more than 150 percent of predicted (ratio of observed to expected diameter 1.5 or more). Aneurysm should be distinguished from ectasia, which represents a diffuse dilation of the aorta less than 50 percent of normal aorta diameter. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: 9/24. (PMID:34211179)
- 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: 8/22. (PMID:34211179)
- Hypopigmentation of the skin (HP:0001010): A reduction of skin color related to a decrease in melanin production and deposition. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Dyslexia (HP:0010522): A learning disorder characterized primarily by difficulties in learning to read and spell. Dyslectic children also exhibit a tendency to read words from right to left and to confuse letters such as b and d whose orientation is important for their identification. Children with dyslexia appear to be impaired in phonemic skills (the ability to associate visual symbols with the sounds they represent). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Neurodegeneration (HP:0002180): Progressive loss of neural cells and tissue. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Suicidal ideation (HP:0031589): Frequent thoughts about or preoccupation with killing oneself. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Diminished ability to concentrate (HP:0031987): The inability to focus or concentrate on a specific task, activity, or object. The subject may find themselves unable to grasp or understand written text and re-reads frequently without understanding. Familiar tasks or activities are severely compromised due to the lack of ability to concentrate. Thinking through multi-step problems is typically very difficult or impossible, leading to avoidance of such activities. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 2/29. (PMID:34211179)
- Allergy (HP:0012393): An allergy is an immune response or reaction to substances that are usually not harmful. Evidence: PCS. Frequency: 3/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: 4/29. (PMID:34211179)
- 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: 4/29. (PMID:34211179)
- Emotional lability (HP:0000712): Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances. Evidence: PCS. Frequency: 8/22. (PMID:34211179)
- 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: 3/29. (PMID:34211179)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Depressed nasal tip (HP:0000437): Decreased distance from the nasal tip to the nasal base. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Bicuspid aortic valve (HP:0001647): The presence of an aortic valve with two instead of the normal three cusps (flaps). Bicuspid aortic valvue is a malformation of a commissure (small space between the attachment of each cusp to the aortic wall) and the adjacent parts of the two corresponding cusps forming a raphe (the fused area of the two underdeveloped cusps turning into a malformed commissure between both cusps; the raphe is a fibrous ridge that extends from the commissure to the free edge of the two underdeveloped, conjoint cusps). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Agitation (HP:0000713): A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 21/24. (PMID:34211179)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Spastic diplegia (HP:0001264): Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: PCS. Frequency: 6/14. (PMID:34211179)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Heart murmur (HP:0030148): An extra or unusual sound heard during a heartbeat caused vibrations resulting from the flow of blood through the heart. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 4/29. (PMID:34211179)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 28/28. (PMID:34211179)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 6/21. (PMID:34211179)
- Hyperbilirubinemia (HP:0002904): An increased amount of bilirubin in the blood. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Restrictive behavior (HP:0000723): Behavior characterized by an abnormal limitation to a few interests and activities. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: PCS. Frequency: 3/22. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- Bifid scrotum (HP:0000048): Midline indentation or cleft of the scrotum. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Broad philtrum (HP:0000289): Distance between the philtral ridges, measured just above the vermilion border, more than 2 standard deviations above the mean, or alternatively, an apparently increased distance between the ridges of the philtrum. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 1/29. (PMID:34211179)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Chorioretinal coloboma (HP:0000567): Absence of a region of the retina, retinal pigment epithelium, and choroid. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Recurrent ear infections (HP:0410018): Increased susceptibility to ear infections as manifested by recurrent episodes of ear infections. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Nuchal cord (HP:0012498): A complication of pregnancy and delivery in which the umbilical cord wraps around the fetal neck once or multiple times. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/29. (PMID:34211179)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Tapered distal phalanges of finger (HP:0009884): A reduction in diameter of the distal phalanx of finger towards the distal end. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Abnormality of the cardiovascular system (HP:0001626): Any abnormality of the cardiovascular system. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- Cupped ear (HP:0000378): Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 4/21. (PMID:34211179)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormal skin pigmentation (HP:0001000): An abnormality of the pigmentation of the skin. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Talipes equinovarus (HP:0001762): Talipes equinovarus (also called clubfoot) typically has four main components: inversion and adduction of the forefoot; inversion of the heel and hindfoot; equinus (limitation of extension) of the ankle and subtalar joint; and internal rotation of the leg. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 4/29. (PMID:34211179)
- Prominent glabella (HP:0002057): Forward protrusion of the glabella. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormality of head or neck (HP:0000152): An abnormality of head and neck. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Hematuria (HP:0000790): The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine). Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Persistent head lag (HP:0032988): The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows: 0 = head drops and stays back, 1 = tries to lift head but drops it back, 2 = able to lift head slightly, 3 = lifts head in line with body, and 4 = head in front of body. This term applies if head lag persists beyond an expected age at a level of 0 or 1. Persistent head lag beyond age 4 mo has been linked to poor outcomes. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- 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: 1/29. (PMID:34211179)
- 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: PCS. Frequency: 4/29. (PMID:34211179)
- Abnormality of the nervous system (HP:0000707): An abnormality of the nervous system. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Juvenile cataract (HP:0001118): A type of cataract that is not apparent at birth but that arises in childhood or adolescence. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Tip-toe gait (HP:0030051): An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Delayed puberty (HP:0000823): Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Back pain (HP:0003418): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the back. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 2/29. (PMID:34211179)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: PCS. Frequency: 3/29. (PMID:34211179)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Otitis media (HP:0000388): Inflammation or infection of the middle ear. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Oval face (HP:0000300): A face with a rounded and slightly elongated outline. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: 1/29. (PMID:34211179)
These phenotypes are associated with the disease developmental delay, impaired speech, and behavioral abnormalities (OMIM:619475).