Phenotypes associated with the disease Kabuki syndrome 1 (OMIM:147920):
- Alobar holoprosencephaly (HP:0006988): A type of holoprosencephaly characterized by the presence of a single ventricle and no separation of the cerebral hemisphere. The single midline ventricle is often greatly enlarged. Evidence: PCS. Frequency: 2/3. (PMID:31282990;PMID:31846209)
- Anal stenosis (HP:0002025): Abnormal narrowing of the anal opening. Evidence: IEA. (OMIM:147920)
- Severe short stature (HP:0003510): A severe degree of short stature, more than -4 SD from the mean corrected for age and sex. Evidence: PCS. Frequency: 11/13. (PMID:25142838;PMID:32083401)
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: PCS. Frequency: 1/6. (PMID:31727177)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 22/43. (PMID:25142838;PMID:24739679;PMID:27573763;PMID:29914387;PMID:31727177;PMID:27991736;PMID:20711175)
- Prominent fingertip pads (HP:0001212): A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist. Evidence: PCS. Frequency: 31/39. (PMID:25142838;PMID:24739679;PMID:29482518;PMID:27922244;PMID:31727177;PMID:24019847;PMID:27991736;PMID:31846209;PMID:32083401)
- 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: 6/24. (PMID:24739679;PMID:31727177;PMID:25896430)
- Malabsorption (HP:0002024): Impaired ability to absorb one or more nutrients from the intestine. Evidence: IEA. (OMIM:147920)
- Renal hypoplasia (HP:0000089): Hypoplasia of the kidney. Evidence: PCS. Frequency: 0/4. (PMID:35060672;PMID:27991736)
- 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: PCS. Frequency: 11/20. (PMID:24739679;PMID:29914387;PMID:31727177;PMID:27991736)
- Unilateral renal agenesis (HP:0000122): A unilateral form of agenesis of the kidney. Evidence: PCS. Frequency: 0/4. (PMID:35060672;PMID:27991736)
- Focal impaired awareness seizure (HP:0002384): Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure. Evidence: PCS. Frequency: 1/1. (PMID:27922244)
- Retinal coloboma (HP:0000480): A notch or cleft of the retina or choroid, located vertically below the optic disc. Evidence: PCS. Frequency: 0/1. (PMID:35060672)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- Ectopic kidney (HP:0000086): A developmental defect in which a kidney is located in an abnormal anatomic position. Evidence: PCS. Frequency: 2/11. (PMID:24739679;PMID:29482518)
- 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: 2/2. (PMID:32083401)
- 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: PCS. Frequency: 5/17. (PMID:31949313;PMID:27991736;PMID:32083401)
- Horseshoe kidney (HP:0000085): A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline. Evidence: PCS. Frequency: 0/4. (PMID:35060672;PMID:27991736)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 5/17. (PMID:29482518;PMID:27573763;PMID:31727177;PMID:25896430)
- Duplicated collecting system (HP:0000081): A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice. Evidence: PCS. Frequency: 0/3. (PMID:27991736)
- Type II pneumocyte hyperplasia (HP:0033328): Increase in the number of type II pneumocytes. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- Aplasia of the semicircular canal (HP:0011381): Absence of the semicircular canal. Evidence: PCS. Frequency: 3/4. (PMID:27991736;PMID:32083401)
- Lobar holoprosencephaly (HP:0006870): A type of holoprosencephaly in which most of the right and left cerebral hemispheres and lateral ventricles are separated but the most rostral aspect of the telencephalon, the frontal lobes, are fused, especially ventrally. Evidence: PCS. Frequency: 1/1. (PMID:31846209)
- 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: 1/7. (PMID:30509212;PMID:31727177)
- 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: 27/31. (PMID:24739679;PMID:30509212;PMID:29482518;PMID:29914387;PMID:27922244;PMID:31727177;PMID:24019847;PMID:25896430;PMID:31846209)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: PCS. Frequency: 10/14. (PMID:30509212;PMID:29482518;PMID:29914387;PMID:25896430;PMID:32083401)
- Finger clinodactyly (HP:0040019). Evidence: PCS. Frequency: 10/10. (PMID:24739679)
- Large earlobe (HP:0009748): Increased volume of the earlobe, that is, abnormally prominent ear lobules. Evidence: PCS. Frequency: 14/14. (PMID:25142838)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. Frequency: 1/6. (PMID:35060672;PMID:27991736;PMID:32083401)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 6/13. (PMID:35060672;PMID:29482518;PMID:31727177;PMID:27991736)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 22/30. (PMID:24739679;PMID:29482518;PMID:29914387;PMID:31727177;PMID:24019847;PMID:25896430;PMID:31846209;PMID:32083401)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 4/4. (PMID:27573763;PMID:27991736)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 7/18. (PMID:31282990;PMID:31727177;PMID:24019847;PMID:25896430;PMID:31846209)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 2/2. (PMID:31282990)
- Premature thelarche (HP:0010314): Premature development of the breasts. Evidence: TAS. (OMIM:147920)
- Bilateral renal hypoplasia (HP:0012584): Two sided hypoplasia of the kidney. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- 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: PCS. Frequency: 6/6. (PMID:35060672;PMID:27991736;PMID:32083401)
- Decreased circulating total IgG concentration (HP:0032132): A reduction beneath the normal level of total immunoglobulin G (IgG) in the blood. Evidence: PCS. Frequency: 2/13. (PMID:25142838)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: PCS. Frequency: 14/14. (PMID:25142838)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 14/21. (PMID:25142838;PMID:31727177;PMID:24019847)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 3/7. (PMID:31727177;PMID:24019847)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 6/20. (PMID:29482518;PMID:27573763;PMID:31727177;PMID:25896430;PMID:32083401)
- Autoimmune thrombocytopenia (HP:0001973): The presence of thrombocytopenia in combination with detection of antiplatelet antibodies. Evidence: IEA. (OMIM:147920)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: PCS. Frequency: 24/30. (PMID:24739679;PMID:35060672;PMID:29482518;PMID:29914387;PMID:31727177;PMID:25896430;PMID:31846209;PMID:32083401)
- Pelvic kidney (HP:0000125): A developmental defect in which a kidney is located in an abnormal anatomic position within the pelvis. Evidence: PCS. Frequency: 0/4. (PMID:35060672;PMID:27991736)
- Multicystic kidney dysplasia (HP:0000003): Multicystic dysplasia of the kidney is characterized by multiple cysts of varying size in the kidney and the absence of a normal pelvicaliceal system. The condition is associated with ureteral or ureteropelvic atresia, and the affected kidney is nonfunctional. Evidence: PCS. Frequency: 1/14. (PMID:24739679;PMID:35060672;PMID:27991736)
- Thoracic scoliosis (HP:0002943). Evidence: PCS. Frequency: 1/1. (PMID:31949313)
- 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:20711175)
- 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: PCS. Frequency: 3/6. (PMID:30509212;PMID:27991736;PMID:32083401)
- Weak cry (HP:0001612). Evidence: PCS. Frequency: 1/1. (PMID:30509212)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/5. (PMID:35060672;PMID:27922244;PMID:27991736)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 9/10. (PMID:35060672;PMID:29914387;PMID:27922244;PMID:24019847;PMID:31846209;PMID:32083401)
- 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: 3/3. (PMID:27991736)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. Frequency: 4/4. (PMID:29482518;PMID:29914387;PMID:24019847)
- Hypoplastic left ventricle (HP:0004383): A severe congenital heart defect characterized by underdevelopment of the left ventricle. Evidence: PCS. Frequency: 1/30. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 4/10. (PMID:35060672;PMID:31949313;PMID:29482518;PMID:32083401)
- Branchial sinus (HP:0100272): A congenital branchial sinus is a remnant of the embryonic branchial arches and their intervening clefts and pouches that has failed to regress completely. Sinuses typically have their external orifice inferior to the ramus of the mandible. They may traverse the parotid gland, and run in close vicinity to the facial nerve in the external auditory canal. Evidence: PCS. Frequency: 2/4. (PMID:32083401)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: PCS. Frequency: 32/36. (PMID:22126750)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/6. (PMID:31727177)
- Nasolacrimal duct obstruction (HP:0000579): Blockage of the lacrimal duct. Evidence: PCS. Frequency: 1/1. (PMID:35060672)
- 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: 7/10. (PMID:29914387;PMID:31727177;PMID:27991736)
- 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: 6/7. (PMID:30509212;PMID:27573763;PMID:27922244;PMID:27991736;PMID:31846209)
- Congenital hypothyroidism (HP:0000851): A type of hypothyroidism with congenital onset. Evidence: PCS. Frequency: 3/6. (PMID:31949313)
- Persistence of primary teeth (HP:0006335): Persistence of the primary teeth beyond the age by which they normally are shed and replaced by the permanent teeth. Evidence: PCS. Frequency: 2/4. (PMID:32083401)
- Thick lower lip vermilion (HP:0000179): Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective). Evidence: PCS. Frequency: 4/4. (PMID:29914387;PMID:27991736)
- Depressed nasal ridge (HP:0000457): Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge. Evidence: PCS. Frequency: 2/6. (PMID:31282990;PMID:32083401)
- Right ventricular hypertrophy (HP:0001667): In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal. Evidence: PCS. Frequency: 1/29. (PMID:25142838;PMID:35060672;PMID:31949313;PMID:27573763;PMID:24019847;PMID:27991736)
- Thick upper lip vermilion (HP:0000215): Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective). Evidence: PCS. Frequency: 0/3. (PMID:31727177)
- Anteriorly placed anus (HP:0001545): Anterior malposition of the anus. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- Renal dysplasia (HP:0000110): The presence of developmental dysplasia of the kidney. Evidence: PCS. Frequency: 0/4. (PMID:35060672;PMID:27991736)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 4/14. (PMID:31727177;PMID:25896430)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 1/1. (PMID:30509212)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/2. (PMID:31282990)
- Vesicoureteral reflux (HP:0000076): Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes. Evidence: PCS. Frequency: 0/3. (PMID:27991736)
- 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: 10/12. (PMID:35060672;PMID:31949313;PMID:27573763;PMID:24019847;PMID:27991736;PMID:32083401)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 9/35. (PMID:25142838;PMID:24739679;PMID:25896430;PMID:27991736)
- Thin vermilion border (HP:0000233): Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips). Evidence: PCS. Frequency: 2/2. (PMID:35060672;PMID:32083401)
- Secundum atrial septal defect (HP:0001684): A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum. Evidence: PCS. Frequency: 0/6. (PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Ureteral duplication (HP:0000073): A developmental anomaly characterized by the presence of two, instead of one, ureter connecting a kidney to the bladder. Evidence: PCS. Frequency: 1/13. (PMID:24739679;PMID:27991736)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: PCS. Frequency: 2/3. (PMID:27991736)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: PCS. Frequency: 7/17. (PMID:24739679;PMID:25896430)
- Renal duplication (HP:0000075): A congenital anomaly of the urinary tract, in which the kidney is duplicated and is drained via two separate renal pelves and ureters. Evidence: PCS. Frequency: 2/13. (PMID:24739679;PMID:27991736)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 4/36. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:31727177;PMID:24019847;PMID:27991736)
- Ureteropelvic junction obstruction (HP:0000074): Blockage of urine flow from the renal pelvis to the proximal ureter. Evidence: PCS. Frequency: 1/1. (PMID:27922244)
- Pulmonary arterial hypertension (HP:0002092): Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position. Evidence: PCS. Frequency: 3/10. (PMID:31949313)
- Scimitar anomaly (HP:0011626): Right pulmonary venous return to the inferior vena cava. Evidence: PCS. Frequency: 1/30. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Telecanthus (HP:0000506): Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi. Evidence: PCS. Frequency: 1/1. (PMID:35060672)
- Chiari type I malformation (HP:0007099): Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line). Evidence: PCS. Frequency: 0/10. (PMID:24739679)
- Prominent eyelashes (HP:0011231): Eyelashes that draw the attention of the viewer due to increased density and/or length and/or curl without meeting the criteria of trichomegaly. Evidence: TAS. (OMIM:147920)
- Mitral stenosis (HP:0001718): An abnormal narrowing of the orifice of the mitral valve. Evidence: PCS. Frequency: 0/6. (PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. Frequency: 2/18. (PMID:24739679;PMID:25896430)
- Cholesteatoma (HP:0009797): Cholesteatoma is a benign but potentially destructive growth consisting of keratinizing epithelium located in the middle ear and/or mastoid process. In cholesteatoma, a skin cyst grows into the middle ear and mastoid. The cyst is not cancerous but can erode tissue and cause destruction of the ear. Evidence: PCS. Frequency: 1/6. (PMID:31727177)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 6/11. (PMID:35060672;PMID:31727177;PMID:27991736;PMID:32083401)
- Eversion of lateral third of lower eyelids (HP:0007655). Evidence: PCS. Frequency: 19/22. (PMID:24739679;PMID:30509212;PMID:29482518;PMID:27573763;PMID:31727177;PMID:24019847;PMID:31846209)
- Decreased circulating IgG2 concentration (HP:0008348): A reduction in immunoglobulin levels of the IgG2 subclass in the blood circulation. Evidence: PCS. Frequency: 1/13. (PMID:25142838)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 8/16. (PMID:35060672;PMID:30509212;PMID:29482518;PMID:31727177;PMID:25896430)
- Aortic valve stenosis (HP:0001650): The presence of a stenosis (narrowing) of the aortic valve. Evidence: PCS. Frequency: 1/30. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 1/6. (PMID:31727177)
- Abnormality of the dentition (HP:0000164): Any abnormality of the teeth. Evidence: IEA. (OMIM:147920)
- Congenital hip dislocation (HP:0001374). Evidence: PCS. Frequency: 6/23. (PMID:24739679;PMID:31727177;PMID:25896430)
- 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: PCS. Frequency: 1/1. (PMID:32083401)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 5/13. (PMID:24739679;PMID:35060672;PMID:31949313;PMID:27922244;PMID:32083401)
- Recurrent aspiration pneumonia (HP:0002100): Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia. Evidence: IEA. (OMIM:147920)
- Median cleft upper lip (HP:0000161): A type of cleft lip presenting as a midline (median) gap in the upper lip. Evidence: PCS. Frequency: 1/2. (PMID:31282990)
- 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: 4/25. (PMID:24739679;PMID:31727177;PMID:25896430;PMID:31846209)
- 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: 22/32. (PMID:24739679;PMID:30509212;PMID:29482518;PMID:25896430;PMID:20711175;PMID:31846209)
- Joint dislocation (HP:0001373): Displacement or malalignment of joints. Evidence: PCS. Frequency: 13/40. (PMID:22126750)
- Decreased memory B cell proportion (HP:0030374): A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV). Evidence: PCS. Frequency: 11/13. (PMID:25142838)
- Interrupted aortic arch (HP:0011611): Non-continuity of the arch of aorta with an atretic point or absent segment. Evidence: PCS. Frequency: 1/30. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Sparse eyebrow (HP:0045075): Decreased density/number of eyebrow hairs. Evidence: PCS. Frequency: 4/8. (PMID:30509212;PMID:27573763;PMID:31727177)
- Cafe-au-lait spot (HP:0000957): Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children. Evidence: IEA. (OMIM:147920)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 6/14. (PMID:31727177;PMID:25896430)
- 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: 3/3. (PMID:27991736)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 1/1. (PMID:30509212)
- 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: 1/20. (PMID:25142838;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Depressed nasal tip (HP:0000437): Decreased distance from the nasal tip to the nasal base. Evidence: PCS. Frequency: 38/49. (PMID:25142838;PMID:24739679;PMID:30509212;PMID:29482518;PMID:27573763;PMID:27922244;PMID:31727177;PMID:24019847;PMID:25896430;PMID:31846209;PMID:32083401)
- 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: 2/7. (PMID:31727177;PMID:32083401)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 2/3. (PMID:29482518;PMID:27573763)
- 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: PCS. Frequency: 5/45. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:31949313;PMID:27573763;PMID:31727177;PMID:24019847;PMID:27991736)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/1. (PMID:27922244)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/1. (PMID:35060672)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: IEA. (OMIM:147920)
- 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: 95/97. (PMID:25142838;PMID:21671394;PMID:29482518;PMID:31727177;PMID:24019847;PMID:25896430)
- Oligodontia (HP:0000677): The absence of six or more teeth from the normal series by a failure to develop. Evidence: PCS. Frequency: 3/3. (PMID:27991736)
- 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: PCS. Frequency: 40/69. (PMID:25142838;PMID:31282990;PMID:30509212;PMID:29914387;PMID:22126750;PMID:20711175;PMID:32083401)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: PCS. Frequency: 3/3. (PMID:30509212;PMID:27573763;PMID:31846209)
- 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: IEA. (OMIM:147920)
- Choanal atresia (HP:0000453): Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral. Evidence: PCS. Frequency: 8/8. (PMID:35060672;PMID:27991736;PMID:32083401)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 0/6. (PMID:31727177)
- 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: 8/25. (PMID:31949313;PMID:29482518;PMID:31727177;PMID:25896430;PMID:31846209)
- 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: 5/19. (PMID:24739679;PMID:29482518;PMID:25896430;PMID:27991736)
- Decreased CD4+ memory T cell proportion (HP:0410386): Decresaed proportion of CD4-positive, alpha-beta memory T cells compared to the total number of T cells in the blood. These cells have the phenotype of CD45RO-positive and CD127-positive. This cell type is also described as being CD25-negative, CD44-high, and CD122-high. Evidence: PCS. Frequency: 8/13. (PMID:25142838)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 1/1. (PMID:27922244)
- 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: 40/42. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:29482518;PMID:29914387;PMID:24019847;PMID:20711175;PMID:32083401)
- Microdontia (HP:0000691): Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth. Evidence: PCS. Frequency: 3/5. (PMID:35060672;PMID:32083401)
- Dimple chin (HP:0010751): A persistent midline depression of the skin over the fat pad of the chin. Evidence: PCS. Frequency: 1/1. (PMID:35060672)
- Subpleural honeycombing (HP:0031631): So-called honeycombs (variably sized cysts in a background of densely scarred tissue) located in the subpleural space. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- Second trimester onset (HP:0034198): This term refers to a phenotypic feature that was first observed prior to birth during the second trimester, which comprises the range of gestational ages from 14 0/7 weeks to 27 6/7 (inclusive). Evidence: PCS. Frequency: 2/2. (PMID:31282990)
- Dental malocclusion (HP:0000689): Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns. Evidence: PCS. Frequency: 1/4. (PMID:32083401)
- 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: PCS. Frequency: 3/3. (PMID:31282990;PMID:31846209)
- Butterfly vertebrae (HP:0003316): A butterfly vertebra (sagittal cleft vertebra or anterior rachischisis) is a sagittal defect in the vertebral body caused by failure of fusion of the two lateral chondrification centers during embryogenesis. The name is based on the appearance of the two hemivertebrae emerging as butterfly wings from the central cleft on x-ray. Evidence: PCS. Frequency: 1/1. (PMID:24019847)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: PCS. Frequency: 6/12. (PMID:24739679;PMID:29482518)
- Anoperineal fistula (HP:0005218): The presence of a fistula (abnormal tunnel) between the anal canal and the perineum. Evidence: IEA. (OMIM:147920)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: PCS. Frequency: 5/35. (PMID:25142838;PMID:35060672;PMID:31949313;PMID:27573763;PMID:31727177;PMID:24019847;PMID:27991736)
- Sparse lateral eyebrow (HP:0005338): Decreased density/number and/or decreased diameter of lateral eyebrow hairs. Evidence: PCS. Frequency: 11/11. (PMID:24739679;PMID:29482518;PMID:25896430;PMID:31846209)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 1/4. (PMID:32083401)
- Wide nose (HP:0000445): Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae. Evidence: PCS. Frequency: 1/1. (PMID:27573763)
- Preauricular pit (HP:0004467): Small indentation anterior to the insertion of the ear. Evidence: PCS. Frequency: 6/12. (PMID:27991736;PMID:20711175;PMID:32083401)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 0/6. (PMID:31727177)
- Single ventricle (HP:0001750): The presence of only one working lower chamber in the heart, usually with a virtual absence of the ventricular septum and usually present in conjunction with double inlet left or right ventricle. Evidence: PCS. Frequency: 0/2. (PMID:35060672;PMID:27573763)
- Absent nipple (HP:0002561): Congenital failure to develop, and absence of, the nipple. Evidence: PCS. Frequency: 5/12. (PMID:31949313;PMID:32083401)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 2/7. (PMID:29482518;PMID:31727177)
- 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: PCS. Frequency: 1/2. (PMID:31282990)
- Unusual bronchiolitis (HP:0011950): Increased susceptibility to bronchiolitis (inflammation of the bronchioles) as manifested by recurrent or severe epsiodes of bronchiolitis. Evidence: PCS. Frequency: 1/1. (PMID:31846209)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 40/64. (PMID:24739679;PMID:31949313;PMID:29482518;PMID:25896430;PMID:22126750)
- 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: 5/36. (PMID:25142838;PMID:24739679;PMID:35060672;PMID:27573763;PMID:31727177;PMID:24019847;PMID:27991736)
- Microtia (HP:0008551): Underdevelopment of the external ear. Evidence: PCS. Frequency: 1/1. (PMID:32083401)
- Crossed fused renal ectopia (HP:0004736): A developmental anomaly in which the kidneys are fused and localized on the same side of the midline. This anomaly is thought to result from disruption of the normal embryologic migration of the kidneys. Evidence: TAS. (OMIM:147920)
- Cupped ear (HP:0000378): Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura). Evidence: PCS. Frequency: 1/3. (PMID:35060672;PMID:27991736;PMID:32083401)
- Hypoplastic nipples (HP:0002557): Underdevelopment of the nipple. Evidence: PCS. Frequency: 5/12. (PMID:31949313;PMID:32083401)
- 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: 3/3. (PMID:30509212;PMID:27922244;PMID:31846209)
- Phimosis (HP:0001741): The male foreskin cannot be fully retracted from the head of the penis. Evidence: PCS. Frequency: 0/1. (PMID:35060672)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/8. (PMID:35060672;PMID:27573763;PMID:31727177)
- Overfolded helix (HP:0000396): A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear. Evidence: PCS. Frequency: 0/1. (PMID:35060672)
- 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: PCS. Frequency: 1/1. (PMID:29914387)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 14/17. (PMID:24739679;PMID:29914387;PMID:31727177)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 4/6. (PMID:35060672;PMID:27991736;PMID:32083401)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 2/3. (PMID:31282990;PMID:32083401)
- Hypoparathyroidism (HP:0000829): A condition caused by a deficiency of parathyroid hormone characterized by hypocalcemia and hyperphosphatemia. Evidence: PCS. Frequency: 4/4. (PMID:32083401)
- Hemolytic anemia (HP:0001878): A type of anemia caused by premature destruction of red blood cells (hemolysis). Evidence: IEA. (OMIM:147920)
- Tetralogy of Fallot (HP:0001636): A congenital cardiac malformation comprising pulmonary stenosis, overriding aorta, ventricular septum defect, and right ventricular hypertrophy. The diagnosis of TOF is made if at least three of the four above mentioned features are present. Evidence: PCS. Frequency: 0/20. (PMID:25142838;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 4/4. (PMID:32083401)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: PCS. Frequency: 1/1. (PMID:27922244)
- 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: PCS. Frequency: 1/1. (PMID:29914387)
- Short 5th finger (HP:0009237): Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger. Evidence: PCS. Frequency: 16/16. (PMID:25142838;PMID:27573763;PMID:27922244)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/1. (PMID:31282990)
- 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: PCS. Frequency: 6/15. (PMID:25142838;PMID:24739679;PMID:31949313;PMID:31727177;PMID:27991736)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 2/2. (PMID:30509212;PMID:27922244)
- 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: PCS. Frequency: 1/1. (PMID:27922244)
- 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: PCS. Frequency: 1/1. (PMID:31949313)
- 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: PCS. Frequency: 1/1. (PMID:29482518)
- 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: PCS. Frequency: 1/1. (PMID:35060672)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: PCS. Frequency: 4/13. (PMID:25142838)
- Intestinal malrotation (HP:0002566): An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis. Evidence: IEA. (OMIM:147920)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: PCS. Frequency: 1/1. (PMID:29914387)
- Abnormal mitral valve morphology (HP:0001633): Any structural anomaly of the mitral valve. Evidence: PCS. Frequency: 0/20. (PMID:25142838;PMID:35060672;PMID:27573763;PMID:24019847;PMID:27991736)