Phenotypes associated with the disease Cornelia de Lange syndrome 1 (OMIM:122470):
- Astigmatism (HP:0000483): A type of refraction error associated with abnormal curvatures on the anterior and/or posterior surface of the cornea. Evidence: IEA. (OMIM:122470)
- Anal atresia (HP:0002023): Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract. Evidence: PCS. Frequency: 1/2. (PMID:21165303;PMID:23304577)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 6/23. (PMID:31337854;PMID:30246735)
- 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:122470)
- Renal hypoplasia (HP:0000089): Hypoplasia of the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:122470)
- 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: 33/38. (PMID:31337854;PMID:36777704;PMID:38284454;PMID:22241092)
- Pyloric stenosis (HP:0002021): Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss. Evidence: IEA. (OMIM:122470)
- Ectopic kidney (HP:0000086): A developmental defect in which a kidney is located in an abnormal anatomic position. Evidence: IEA. (OMIM:122470)
- 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: IEA. (OMIM:122470)
- 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: 9/11. (PMID:21165303;PMID:36777704;PMID:32074972;PMID:38284454)
- 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: 25/40. (PMID:21165303;PMID:31337854;PMID:20358602;PMID:22241092)
- 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: 1/11. (PMID:20358602)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/2. (PMID:36777704)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:122470)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: PCS. Frequency: 29/30. (PMID:36777704;PMID:32074972;PMID:25447906;PMID:22241092;PMID:20358602;PMID:38284454)
- Proximal placement of thumb (HP:0009623): Proximal mislocalization of the thumb. Evidence: PCS. Frequency: 20/47. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:22241092;PMID:20358602;PMID:38284454)
- Short sternum (HP:0000879): Decreased inferosuperior length of the sternum. Evidence: IEA. (OMIM:122470)
- Sporadic (HP:0003745): Cases of the disease in question occur without a previous family history, i.e., as isolated cases without being transmitted from a parent and without other siblings being affected. Evidence: IEA. (OMIM:122470)
- Hiatus hernia (HP:0002036): The presence of a hernia in which the upper part of the stomach, i.e., mainly the gastric cardia protrudes through the diaphragmatic esophageal hiatus. Evidence: IEA. (OMIM:122470)
- 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: 36/38. (PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:38284454;PMID:22241092)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 39/46. (PMID:31337854;PMID:36777704;PMID:32074972;PMID:25447906;PMID:38284454;PMID:22241092)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 1/1. (PMID:23304577)
- 2-3 toe syndactyly (HP:0004691): Syndactyly with fusion of toes two and three. Evidence: IEA. (OMIM:122470)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:122470)
- Dislocated radial head (HP:0003083): A dislocation of the head of the radius from its socket in the elbow joint. Evidence: IEA. (OMIM:122470)
- 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: 10/25. (PMID:20358602;PMID:22241092;PMID:38284454)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 42/44. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:30246735;PMID:22241092;PMID:38284454)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: IEA. (OMIM:122470)
- 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: 23/39. (PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:38284454;PMID:22241092)
- Conductive hearing impairment (HP:0000405): An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound. Evidence: TAS. (OMIM:122470)
- Supernumerary ribs (HP:0005815): The presence of more than 12 rib pairs. Evidence: IEA. (OMIM:122470)
- Lacrimal duct stenosis (HP:0007678): Narrowing of a tear duct (lacrimal duct). Evidence: PCS. Frequency: 3/5. (PMID:22241092)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: IEA. (OMIM:122470)
- 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:25447906)
- 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: PCS. Frequency: 4/5. (PMID:36777704;PMID:38284454)
- 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: 9/19. (PMID:21165303;PMID:32074972;PMID:25447906;PMID:38284454;PMID:22241092)
- Weak cry (HP:0001612). Evidence: PCS. Frequency: 1/1. (PMID:23304577)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/1. (PMID:23304577)
- Hypoplastic radial head (HP:0003997). Evidence: IEA. (OMIM:122470)
- 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: 2/2. (PMID:21165303;PMID:30246735)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 1/7. (PMID:22241092)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 6/6. (PMID:21165303;PMID:23304577;PMID:30246735;PMID:32074972)
- 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: PCS. Frequency: 37/46. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:25447906;PMID:22241092;PMID:38284454)
- Malrotation of colon (HP:0004785): An anatomical anomaly that results from an abnormal rotation of the gut as it returns to the abdominal cavity during embryogenesis. Evidence: IEA. (OMIM:122470)
- 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: 32/41. (PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:22241092;PMID:38284454)
- 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: 3/11. (PMID:20358602)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/11. (PMID:20358602)
- Hypoplastic left ventricle (HP:0004383): A severe congenital heart defect characterized by underdevelopment of the left ventricle. Evidence: PCS. Frequency: 0/24. (PMID:31337854;PMID:30246735)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 7/7. (PMID:22241092)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: PCS. Frequency: 14/19. (PMID:31337854)
- Concave nasal ridge (HP:0011120): Nasal ridge curving posteriorly to an imaginary line that connects the nasal root and tip. Evidence: PCS. Frequency: 4/5. (PMID:36777704;PMID:32074972)
- Motor stereotypy (HP:0000733): Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose. Evidence: PCS. Frequency: 2/2. (PMID:36777704)
- 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: 36/44. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:30246735;PMID:32074972;PMID:25447906;PMID:22241092;PMID:38284454)
- 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: 3/11. (PMID:20358602)
- Curly eyelashes (HP:0007665): Abnormally curly or curved eyelashes. Evidence: PCS. Frequency: 33/39. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:25447906;PMID:38284454)
- 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: 12/47. (PMID:31337854;PMID:30246735;PMID:32074972;PMID:22241092;PMID:38284454;PMID:20358602)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 6/7. (PMID:21165303;PMID:36777704;PMID:38284454)
- Hypoplastic labia majora (HP:0000059): Undergrowth of the outer labia. Evidence: PCS. Frequency: 1/11. (PMID:20358602)
- Anteriorly placed anus (HP:0001545): Anterior malposition of the anus. Evidence: PCS. Frequency: 1/12. (PMID:21165303;PMID:20358602)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:122470)
- 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: 29/35. (PMID:31337854;PMID:36777704;PMID:25447906;PMID:22241092;PMID:20358602)
- Phocomelia (HP:0009829): Missing or malformed long bones of the extremities with the distal parts (such as hands and/or feet) connected to the variably shortened or even absent extremity, leading to a flipper-like appearance, as opposed to other forms of limb malformations were either the entire limb is missing (such as amelia), or the distal part of a limb is absent (peromelia). Evidence: PCS. Frequency: 1/34. (PMID:23304577;PMID:31337854;PMID:32074972;PMID:22241092)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 14/24. (PMID:31337854;PMID:30246735)
- Pneumonia (HP:0002090): Inflammation of any part of the lung parenchyma. Evidence: IEA. (OMIM:122470)
- Oligodactyly (HP:0012165): A developmental defect resulting in the presence of fewer than the normal number of digits. Evidence: PCS. Frequency: 12/53. (PMID:21165303;PMID:31337854;PMID:36777704;PMID:32074972;PMID:22241092;PMID:38284454;PMID:20358602)
- 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: 3/32. (PMID:23304577;PMID:31337854;PMID:36777704;PMID:22241092)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: PCS. Frequency: 1/11. (PMID:20358602)
- Coronal hypospadias (HP:0008743): A mild form of hypospadias in which the urethra opens just under the corona glandis, that is, where the head of the penis meets the shaft. Evidence: PCS. Frequency: 1/1. (PMID:23304577)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: PCS. Frequency: 13/21. (PMID:31337854;PMID:36777704)
- Syndactyly (HP:0001159): Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism". Evidence: PCS. Frequency: 5/12. (PMID:21165303;PMID:20358602)
- 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: 16/19. (PMID:31337854)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 27/46. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:38284454;PMID:22241092;PMID:20358602)
- Optic disc coloboma (HP:0000588): A cleft of the optic nerve that extends inferiorly. Evidence: IEA. (OMIM:122470)
- Micromelia (HP:0002983): The presence of abnormally small extremities. Evidence: IEA. (OMIM:122470)
- Toe syndactyly (HP:0001770): Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism". Evidence: PCS. Frequency: 3/7. (PMID:23304577;PMID:32074972;PMID:22241092)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:32074972)
- Delayed eruption of teeth (HP:0000684): Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age. Evidence: IEA. (OMIM:122470)
- Limited elbow extension (HP:0001377): Limited ability to straighten the arm at the elbow joint. Evidence: PCS. Frequency: 12/34. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:22241092)
- Short foot (HP:0001773): A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective). Evidence: PCS. Frequency: 6/6. (PMID:38284454;PMID:22241092)
- 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: 12/37. (PMID:21165303;PMID:31337854;PMID:32074972;PMID:20358602)
- 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: 1/11. (PMID:20358602)
- Cleft lip (HP:0410030): A gap in the lip or lips. Evidence: PCS. Frequency: 0/25. (PMID:21165303;PMID:23304577;PMID:31337854)
- Finger aplasia (HP:0009380): A developmental defect resulting in the presence of fewer than the normal number of fingers (i.e., aplasia of one or more fingers). Evidence: IEA. (OMIM:122470)
- Abnormal incisura morphology (HP:0031228): An abnormal shape of the incisura, defined as the narrowed downward continuation of the conchal space bounded anteriorly by the borders of the tragus, posteriorly by the antitragus, and along its lower lateral margins and inferior boundary by the connection between the first two. The upper boundary is a somewhat arbitrary line crossing from the apices of the antitragus and the tragus. Evidence: IEA. (PMID:19764039)
- 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: 15/19. (PMID:23304577;PMID:36777704;PMID:32074972;PMID:38284454;PMID:22241092)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 11/19. (PMID:31337854)
- 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: 0/24. (PMID:31337854;PMID:30246735)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 20/32. (PMID:31337854;PMID:25447906;PMID:22241092)
- 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: 0/1. (PMID:30246735)
- Pulmonic stenosis (HP:0001642): A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis). Evidence: PCS. Frequency: 6/41. (PMID:31337854;PMID:30246735;PMID:22241092;PMID:20358602)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 39/56. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:30246735;PMID:32074972;PMID:25447906;PMID:22241092;PMID:38284454;PMID:20358602)
- 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: 34/40. (PMID:31337854;PMID:36777704;PMID:25447906;PMID:22241092;PMID:38284454;PMID:20358602)
- 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: 7/46. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:30246735;PMID:25447906;PMID:20358602;PMID:22241092)
- 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: IEA. (OMIM:122470)
- Heart murmur (HP:0030148): An extra or unusual sound heard during a heartbeat caused vibrations resulting from the flow of blood through the heart. Evidence: PCS. Frequency: 5/11. (PMID:20358602)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 9/9. (PMID:21165303;PMID:23304577;PMID:36777704;PMID:30246735;PMID:38284454)
- 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: IEA. (OMIM:122470)
- 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: 11/19. (PMID:21165303;PMID:36777704;PMID:30246735;PMID:22241092;PMID:20358602)
- Hypoplastic male external genitalia (HP:0000050): Underdevelopment of part or all of the male external reproductive organs (which include the penis, the scrotum and the urethra). Evidence: IEA. (OMIM:122470)
- 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: 42/46. (PMID:31337854;PMID:36777704;PMID:32074972;PMID:20358602;PMID:22241092)
- Low anterior hairline (HP:0000294): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella. Evidence: PCS. Frequency: 12/16. (PMID:23304577;PMID:36777704;PMID:32074972;PMID:38284454;PMID:22241092)
- 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: 1/11. (PMID:20358602)
- 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: 9/25. (PMID:31337854;PMID:36777704;PMID:22241092)
- Cutis marmorata (HP:0000965): A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather. Evidence: PCS. Frequency: 4/6. (PMID:22241092)
- Elbow flexion contracture (HP:0002987): An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position. Evidence: IEA. (OMIM:122470)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: PCS. Frequency: 1/3. (PMID:32074972)
- Cleft upper lip (HP:0000204): A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development. Evidence: TAS. (OMIM:122470)
- Hypoplasia of the radius (HP:0002984): Underdevelopment of the radius. Evidence: IEA. (OMIM:122470)
- 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: 2/18. (PMID:30246735;PMID:22241092;PMID:20358602)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 9/32. (PMID:31337854;PMID:38284454;PMID:22241092)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/6. (PMID:22241092)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 3/5. (PMID:36777704;PMID:25447906)
- 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: 3/42. (PMID:23304577;PMID:31337854;PMID:30246735;PMID:20358602;PMID:22241092)
- 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: PCS. Frequency: 34/42. (PMID:21165303;PMID:31337854;PMID:36777704;PMID:30246735;PMID:32074972;PMID:38284454;PMID:22241092)
- Hypoplastic nipples (HP:0002557): Underdevelopment of the nipple. Evidence: IEA. (OMIM:122470)
- Congenital diaphragmatic hernia (HP:0000776): The presence of a hernia of the diaphragm present at birth. Evidence: PCS. Frequency: 1/30. (PMID:31337854;PMID:36777704;PMID:32074972;PMID:38284454)
- Cardiomegaly (HP:0001640): Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. Evidence: PCS. Frequency: 1/19. (PMID:21165303;PMID:30246735;PMID:22241092;PMID:20358602)
- Reduced renal corticomedullary differentiation (HP:0005565): Reduced differentiation between renal cortex and medulla on diagnostic imaging. Evidence: IEA. (OMIM:122470)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 30/43. (PMID:23304577;PMID:31337854;PMID:30246735;PMID:25447906;PMID:22241092;PMID:38284454)
- Duplication of phalanx of hallux (HP:0010066): Partial or complete duplication of one or more phalanx of big toe. Evidence: PCS. Frequency: 1/8. (PMID:38284454)
- 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: 1/24. (PMID:31337854;PMID:30246735)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 39/52. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:30246735;PMID:22241092;PMID:38284454;PMID:20358602)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 27/52. (PMID:21165303;PMID:31337854;PMID:36777704;PMID:32074972;PMID:20358602;PMID:38284454;PMID:22241092)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 46/49. (PMID:21165303;PMID:23304577;PMID:31337854;PMID:36777704;PMID:32074972;PMID:30246735;PMID:25447906;PMID:22241092;PMID:38284454)
- 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: 2/24. (PMID:23304577;PMID:31337854)
- Otitis media (HP:0000388): Inflammation or infection of the middle ear. Evidence: IEA. (OMIM:122470)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:122470)
- 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: 15/25. (PMID:23304577;PMID:31337854;PMID:32074972;PMID:38284454;PMID:20358602)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: PCS. Frequency: 5/26. (PMID:31337854;PMID:22241092)