Phenotypes associated with the disease neurodevelopmental disorder with variable familial hypercholanemia (OMIM:621016):
- Decreased body weight (HP:0004325): Abnormally low body weight. Evidence: PCS. Frequency: 0/8. (PMID:39471804)
- 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: 3/12. (PMID:39471804)
- 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: 2/10. (PMID:39471804)
- 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: 1/9. (PMID:39471804)
- Unilateral renal agenesis (HP:0000122): A unilateral form of agenesis of the kidney. Evidence: PCS. Frequency: 1/8. (PMID:39471804)
- 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: 3/9. (PMID:39471804)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 3/14. (PMID:39471804)
- Polydactyly (HP:0010442): A congenital anomaly characterized by the presence of supernumerary fingers or toes. Evidence: PCS. Frequency: 1/14. (PMID:39471804)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 4/13. (PMID:39471804)
- Deep palmar crease (HP:0006191): Excessively deep creases of the palm. Evidence: PCS. Frequency: 1/14. (PMID:39471804)
- Hemivertebrae (HP:0002937): Absence of one half of the vertebral body. Evidence: PCS. Frequency: 1/3. (PMID:39471804)
- Hypertrichosis (HP:0000998): Hypertrichosis is increased hair growth that is abnormal in quantity or location. Evidence: PCS. Frequency: 1/12. (PMID:39471804)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 4/10. (PMID:39471804)
- Short hard palate (HP:0010290): Distance between the labial point of the incisive papilla to the midline junction of the hard and soft palate more than 2 SD below the mean (objective) or apparently decreased length of the hard palate (subjective). Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/7. (PMID:39471804)
- 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: 1/9. (PMID:39471804)
- 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: 5/12. (PMID:39471804)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 1/10. (PMID:39471804)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/10. (PMID:39471804)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 6/13. (PMID:39471804)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/12. (PMID:39471804)
- Bifid nose (HP:0011803): Visually assessable vertical indentation, cleft, or depression of the nasal bridge, ridge and tip. Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 2/10. (PMID:39471804)
- Recurrent skin infections (HP:0001581): Infections of the skin that happen multiple times. Evidence: PCS. Frequency: 0/8. (PMID:39471804)
- Low-grade vesicoureteral reflux (HP:0033733): Vesicoureteral reflux without dilation of the renal calyces (Grade I-II). Evidence: PCS. Frequency: 6/8. (PMID:39471804)
- Overlapping fingers (HP:0010557): A finger resting on the dorsal surface of an adjacent digit when the hand is at rest. Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- Joint contracture (HP:0034392): A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part. Evidence: PCS. Frequency: 0/13. (PMID:39471804)
- Hip dislocation (HP:0002827): Displacement of the femur from its normal location in the hip joint. Evidence: PCS. Frequency: 1/3. (PMID:39471804)
- Autosomal recessive inheritance (HP:0000007): 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:39471804)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 2/14. (PMID:39471804)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 2/9. (PMID:39471804)
- 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: 0/11. (PMID:39471804)
- 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: 1/10. (PMID:39471804)
- Dilatation of the renal pelvis (HP:0010946): The presence of dilatation of the renal pelvis. Evidence: PCS. Frequency: 1/8. (PMID:39471804)
- Deep philtrum (HP:0002002): Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border. Evidence: PCS. Frequency: 9/12. (PMID:39471804)
- Increased total bilirubin (HP:0003573): Increased concentration of total (conjugated and unconjugated) bilirubin in the blood. Evidence: PCS. Frequency: 1/13. (PMID:39471804)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 5/12. (PMID:39471804)
- Bilateral coxa valga (HP:0010665): The presence of bilateral coxa valga. Evidence: PCS. Frequency: 1/3. (PMID:39471804)
- Increased serum bile acid concentration (HP:0012202): An increase in the concentration of bile acid in the blood. Evidence: PCS. Frequency: 6/6. (PMID:39471804)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 4/13. (PMID:39471804)
- Recurrent pancreatitis (HP:0100027): A recurrent form of pancreatitis. Evidence: PCS. Frequency: 1/10. (PMID:39471804)
- 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: 1/14. (PMID:39471804)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/10. (PMID:39471804)
- 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: 2/14. (PMID:39471804)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: PCS. Frequency: 2/14. (PMID:39471804)
- 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: 0/14. (PMID:39471804)
- Stereotypical hand wringing (HP:0012171): Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement. Evidence: PCS. Frequency: 1/9. (PMID:39471804)
- 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: PCS. Frequency: 1/11. (PMID:39471804)
- 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: 10/10. (PMID:39471804)
- Everted lower lip vermilion (HP:0000232): An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view. Evidence: PCS. Frequency: 9/14. (PMID:39471804)
- Open mouth (HP:0000194): A facial appearance characterized by a permanently or nearly permanently opened mouth. Evidence: PCS. Frequency: 8/12. (PMID:39471804)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: PCS. Frequency: 0/4. (PMID:39471804)
- Rib fusion (HP:0000902): Complete or partial merging of adjacent ribs. Evidence: PCS. Frequency: 1/3. (PMID:39471804)
- 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: 4/13. (PMID:39471804)
- Pruritus (HP:0000989): Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus. Evidence: PCS. Frequency: 9/14. (PMID:39471804)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: PCS. Frequency: 2/9. (PMID:39471804)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 3/14. (PMID:39471804)
- 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: 2/9. (PMID:39471804)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 3/14. (PMID:39471804)
- 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: 2/14. (PMID:39471804)
- 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: 7/13. (PMID:39471804)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/10. (PMID:39471804)
- 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: 1/9. (PMID:39471804)
- Elevated circulating alkaline phosphatase concentration (HP:0003155): Abnormally increased serum levels of alkaline phosphatase activity. Evidence: PCS. Frequency: 12/13. (PMID:39471804)
- Breath-holding spell (HP:6000950): A benign paroxysmal nonepileptic disorder occurring in healthy children 6 to 48 months of age. The episodes start with a provocation such as emotional upset or minor injury, and might progress to breath holding, cyanosis, and syncope. Evidence: PCS. Frequency: 1/1. (PMID:39471804)
- 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: 11/11. (PMID:39471804)
- Myoclonic seizure (HP:0032794): A myoclonic seizure is a type of motor seizure characterized by 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: PCS. Frequency: 1/1. (PMID:39471804)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/7. (PMID:39471804)
- 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: 4/14. (PMID:39471804)
- 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: 1/3. (PMID:39471804)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: PCS. Frequency: 10/10. (PMID:39471804)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/14. (PMID:39471804)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 1/14. (PMID:39471804)
- 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: 14/14. (PMID:39471804)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/8. (PMID:39471804)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 3/12. (PMID:39471804)
- 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: 7/13. (PMID:39471804)
- 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: 11/12. (PMID:39471804)
- Elevated gamma-glutamyltransferase level (HP:0030948): Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues. Evidence: PCS. Frequency: 3/11. (PMID:39471804)
- Abnormal cranial nerve physiology (HP:0031910): A functional abnormality affecting one or more of the cranial nerves, which emerge directly from the brain stem. Evidence: PCS. Frequency: 0/6. (PMID:39471804)
- Camptodactyly (HP:0012385): The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension. Evidence: PCS. Frequency: 1/1. (PMID:39471804)
- Conjugated hyperbilirubinemia (HP:0002908). Evidence: PCS. Frequency: 4/11. (PMID:39471804)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 1/4. (PMID:39471804)
- 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: 2/9. (PMID:39471804)
- 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: 5/14. (PMID:39471804)
- 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: 0/3. (PMID:39471804)
- 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: 2/14. (PMID:39471804)
- Floppy infant (HP:0008947): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: PCS. Frequency: 1/9. (PMID:39471804)
- 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: 1/1. (PMID:39471804)
- Preauricular skin tag (HP:0000384): A rudimentary tag of skin often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear). Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- Antenatal onset (HP:0030674): Onset prior to birth. Evidence: PCS. Frequency: 1/7. (PMID:39471804)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/2. (PMID:39471804)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 1/12. (PMID:39471804)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 1/14. (PMID:39471804)
- Low hanging columella (HP:0009765): Columella extending inferior to the level of the nasal base, when viewed from the side. Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 0/7. (PMID:39471804)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: PCS. Frequency: 0/14. (PMID:39471804)
- 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: 1/14. (PMID:39471804)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 11/12. (PMID:39471804)
- Steatorrhea (HP:0002570): Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats. Evidence: PCS. Frequency: 1/10. (PMID:39471804)
- Cholelithiasis (HP:0001081): Hard, pebble-like deposits that form within the gallbladder. Evidence: PCS. Frequency: 4/13. (PMID:39471804)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 3/5. (PMID:39471804)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 2/14. (PMID:39471804)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 1/8. (PMID:39471804)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 2/3. (PMID:39471804)
- 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: 2/7. (PMID:39471804)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 3/14. (PMID:39471804)