- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: Very frequent (HP:0040281). (ORPHA:369837)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- Slender long bone (HP:0003100): Reduced diameter of a long bone. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- Abnormal skeletal morphology (HP:0011842): An abnormality of the form, structure, or size of the skeletal system. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:369837)
- 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: Very frequent (HP:0040281). (ORPHA:369837)
- Abnormality of the urinary system (HP:0000079): An abnormality of the urinary system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Nephrocalcinosis (HP:0000121): Nephrocalcinosis is the deposition of calcium salts in renal parenchyma. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- 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: Frequent (HP:0040282). (ORPHA:369837)
- 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: Frequent (HP:0040282). (ORPHA:369837)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- 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: Frequent (HP:0040282). (ORPHA:369837)
- 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: Frequent (HP:0040282). (ORPHA:369837)
- Hypercalciuria (HP:0002150). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Downturned corners of mouth (HP:0002714): A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Hypercalcemia (HP:0003072): The concentration of calcium in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Decreased circulating alkaline phosphatase activity (HP:0003282): Concentration or activity of alkaline phosphatase outside the upper or lower limtis of normal in the blood circulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Congenital megaureter (HP:0008676): A developmental disturbance with extreme ureteral dilatation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Upper limb undergrowth (HP:0009824): Arm shortening because of underdevelopment of one or more bones of the upper extremity. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Generalized tonic seizure (HP:0010818): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Abnormal eye physiology (HP:0012373): A functional anomaly of the eye. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:369837)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Renal dysplasia (HP:0000110): The presence of developmental dysplasia of the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- 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: Occasional (HP:0040283). (ORPHA:369837)
- 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:369837)
- 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:369837)
- Precocious puberty (HP:0000826): The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Hypoparathyroidism (HP:0000829): A condition caused by a deficiency of parathyroid hormone characterized by hypocalcemia and hyperphosphatemia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Craniosynostosis (HP:0001363): Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Restrictive cardiomyopathy (HP:0001723): Restrictive left ventricular physiology is characterized by a pattern of ventricular filling in which increased stiffness of the myocardium causes ventricular pressure to rise precipitously with only small increases in volume, defined as restrictive ventricular physiology in the presence of normal or reduced diastolic volumes (of one or both ventricles), normal or reduced systolic volumes, and normal ventricular wall thickness. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- 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:369837)
- Abnormal lung lobation (HP:0002101): A developmental defect in the formation of pulmonary lobes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Exaggerated cupid's bow (HP:0002263): More pronounced paramedian peaks and median notch of the Cupid's bow. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Decreased circulating IgM concentration (HP:0002850): An abnormally decreased level of immunoglobulin M (IgM) in blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Premature loss of teeth (HP:0006480): Exfoliation of a tooth more than 2 SD earlier than the normal age for the deciduous teeth and not related to traume or neglect. Exfoliation of a permanent tooth is per se abnormal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Jerky head movements (HP:0006961). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Central sleep apnea (HP:0010536): Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- EEG with spike-wave complexes (HP:0010850): Complexes of spikes (<70 ms) and sharp waves (70-200 ms), which are sharp transient waves that have a strong association with epilepsy, in cerebral electrical activity recorded along the scalp by electroencephalography (EEG). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- EEG with generalized sharp slow waves (HP:0011199): EEG with generalized sharp transient waves of a duration between 80 and 200 msec followed by a slow wave. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Nasogastric tube feeding in infancy (HP:0011470): Feeding problem necessitating nasogastric tube feeding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Abnormal gastrointestinal tract morphology (HP:0012718): Abnormal structure of the gastrointestinal tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Downgaze palsy (HP:0025330): A limitation of the ability to direct one's gaze below the horizontal meridian. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
- Posterior staphyloma (HP:0030856): A localized defect in the posterior eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:369837)
These phenotypes are associated with the disease Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome (ORPHA:369837).