Phenotypes associated with the disease Alagille syndrome due to a JAG1 point mutation (OMIM:118450):
- Stroke (HP:0001297): Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain. Evidence: TAS. (OMIM:118450)
- 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: 1/4. (PMID:34071626)
- 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: IEA. (OMIM:118450)
- Renal hypoplasia (HP:0000089): Hypoplasia of the kidney. Evidence: TAS. (OMIM:118450)
- Axenfeld anomaly (HP:0001492): Axenfeld's anomaly is a bilateral disorder characterized by a prominent, anteriorly displaced Schwalbe's line (posterior embryotoxon) and peripheral iris strands which span the anterior chamber angle to attach to Schwalbe's line. Evidence: IEA. (OMIM:118450)
- 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: 1/1. (PMID:31157196)
- Microcornea (HP:0000482): A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood. Evidence: TAS. (OMIM:118450)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 3/5. (PMID:31157196;PMID:34071626)
- 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: 2/187. (PMID:12509572)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. (OMIM:118450)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/4. (PMID:34071626)
- Hemivertebrae (HP:0002937): Absence of one half of the vertebral body. Evidence: IEA. (OMIM:118450)
- Typified by incomplete penetrance (HP:0003829): Description of conditions in which not all individuals with a given genotype exhibit the disease. Penetrance is the proportion that develop disease given a lifespan of 80 years. Evidence: TAS. (OMIM:118450)
- 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: 1/1. (PMID:34071626)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: IEA. (OMIM:118450)
- Multiple small medullary renal cysts (HP:0008659): The presence of many cysts in the medulla of the kidney. Evidence: IEA. (OMIM:118450)
- Renal artery stenosis (HP:0001920): The presence of stenosis of the renal artery. Evidence: PCS. Frequency: 2/187. (PMID:12509572)
- Hepatocellular carcinoma (HP:0001402): A kind of neoplasm of the liver that originates in hepatocytes and presents macroscopically as a soft and hemorrhagic tan mass in the liver. Evidence: IEA. (OMIM:118450)
- Abnormal rib morphology (HP:0000772): An anomaly of the rib. Evidence: IEA. (OMIM:118450)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: IEA. (OMIM:118450)
- Hypercholesterolemia (HP:0003124): An increased concentration of cholesterol in the blood. Evidence: IEA. (OMIM:118450)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/1. (PMID:34071626)
- Focal segmental glomerulosclerosis (HP:0000097): Segmental accumulation of scar tissue in individual (but not all) glomeruli. Evidence: PCS. Frequency: 2/187. (PMID:12509572)
- Exocrine pancreatic insufficiency (HP:0001738): Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes. Evidence: TAS. (OMIM:118450)
- Peripheral pulmonary artery stenosis (HP:0004969): Stenosis of a peripheral branch of the pulmonary artery. Evidence: PCS. Frequency: 5/5. (PMID:31157196;PMID:34071626)
- 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: TAS. (OMIM:118450)
- 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:9207787)
- 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: IEA. Frequency: 1/1. (PMID:34071626)
- Triangular face (HP:0000325): Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin. Evidence: PCS. Frequency: 1/1. (PMID:34071626)
- Stage 5 chronic kidney disease (HP:0003774): A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine. Evidence: PCS. Frequency: 4/187. (PMID:12509572)
- Cholestasis (HP:0001396): Impairment of bile flow due to obstruction in bile ducts. Evidence: PCS. Frequency: 4/4. (PMID:34071626)
- 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. (OMIM:118450)
- Band keratopathy (HP:0000585): An abnormality of the cornea characterized by the deposition of calcium in a band across the central cornea, leading to decreased vision, foreign body sensation, and ocular irritation. Evidence: TAS. (OMIM:118450)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 38/174. (PMID:12509572)
- Cirrhosis (HP:0001394): A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function. Evidence: TAS. (OMIM:118450)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: IEA. (OMIM:118450)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:118450)
- 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: IEA. (OMIM:118450)
- Renal tubular acidosis (HP:0001947): Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis. Evidence: PCS. Frequency: 7/187. (PMID:22105858)
- Reduced number of intrahepatic bile ducts (HP:0006571): The presence of reduced numbers of intrahepatic bile duct than normal. Evidence: PCS. Frequency: 4/4. (PMID:34071626)
- Concave nasal ridge (HP:0011120): Nasal ridge curving posteriorly to an imaginary line that connects the nasal root and tip. Evidence: PCS. Frequency: 1/1. (PMID:31157196)
- Short distal phalanx of finger (HP:0009882): Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger. Evidence: IEA. (OMIM:118450)
- 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: 1/1. (PMID:34071626)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 1/1. (PMID:31157196)
- Butterfly vertebral arch (HP:0004617): Butterfly vertebrae have a cleft through the body of the vertebrae and a funnel shape at the ends. Evidence: PCS. Frequency: 1/4. (PMID:34071626)
- 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: 1/1. (PMID:31157196)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: TAS. (OMIM:118450)
- Chorioretinal atrophy (HP:0000533): Atrophy (wasting) of the choroid and retinal layers of the fundus. Evidence: IEA. (OMIM:118450)
- Renal dysplasia (HP:0000110): The presence of developmental dysplasia of the kidney. Evidence: PCS. Frequency: 43/187. (PMID:22105858)
- Abnormal anterior chamber morphology (HP:0000593): Abnormality of the anterior chamber, which is the space in the eye that is behind the cornea and in front of the iris. Evidence: IEA. (OMIM:118450)
- Papillary thyroid carcinoma (HP:0002895): The presence of a papillary adenocarcinoma of the thyroid gland. Evidence: IEA. (OMIM:118450)
- 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: 6/187. (PMID:22105858)
- 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: 1/1. (PMID:31157196)
- Long nose (HP:0003189): Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base. Evidence: PCS. Frequency: 1/1. (PMID:34071626)
- Hypoplasia of the ulna (HP:0003022): Underdevelopment of the ulna. Evidence: IEA. (OMIM:118450)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:118450)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: IEA. (OMIM:118450)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 1/1. (PMID:31157196)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: TAS. (OMIM:118450)
- Posterior embryotoxon (HP:0000627): A posterior embryotoxon is the presence of a prominent and anteriorly displaced line of Schwalbe. Evidence: PCS. Frequency: 1/4. (PMID:34071626)
- 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: IEA. (OMIM:118450)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 1/1. (PMID:31157196)
- 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: IEA. (OMIM:118450)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: IEA. (OMIM:118450)