- Constriction of peripheral visual field (HP:0001133): An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye. Evidence: PCS. Frequency: 1/7. (PMID:30368668)
- 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: 11/27. (PMID:29469822;PMID:30368668)
- Palmoplantar cutis laxa (HP:0007517): Loose, wrinkled skin of hands and feet. Evidence: PCS. Frequency: 4/7. (PMID:30368668)
- 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: 3/20. (PMID:29469822)
- 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: 1/7. (PMID:30368668)
- Anterior polar cataract (HP:0001134): A polar cataract that affects the anterior pole of the lens. Evidence: PCS. Frequency: 1/20. (PMID:29469822)
- 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: 14/24. (PMID:29469822;PMID:30368668)
- 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: 0/5. (PMID:30368668)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/22. (PMID:29469822;PMID:30368668)
- Relative macrocephaly (HP:0004482): A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account. Evidence: PCS. Frequency: 4/7. (PMID:30368668)
- Sparse eyebrow (HP:0045075): Decreased density/number of eyebrow hairs. Evidence: PCS. Frequency: 5/7. (PMID:30368668)
- Shield chest (HP:0000914): A broad chest. Evidence: PCS. Frequency: 12/15. (PMID:29469822)
- 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: PCS. Frequency: 1/7. (PMID:30368668)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/18. (PMID:29469822)
- Abnormality of coagulation (HP:0001928): An abnormality of the process of blood coagulation. That is, altered ability or inability of the blood to clot. Evidence: PCS. Frequency: 0/4. (PMID:30368668)
- 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: 1/4. (PMID:30368668)
- 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: 2/20. (PMID:29469822)
- 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: 13/22. (PMID:29469822;PMID:30368668)
- Hyperpigmentation of the skin (HP:0000953): A darkening of the skin related to an increase in melanin production and deposition. Evidence: PCS. Frequency: 4/4. (PMID:30368668)
- 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: 1/7. (PMID:30368668)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: PCS. Frequency: 5/9. (PMID:29469822)
- 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: 4/27. (PMID:29469822;PMID:30368668)
- 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: 4/6. (PMID:30368668)
- 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: 14/14. (PMID:29469822)
- Melanocytic nevus (HP:0000995): A oval and round, colored (usually medium-to dark brown, reddish brown, or flesh colored) lesion. Typically, a melanocytic nevus is less than 6 mm in diameter, but may be much smaller or larger. Evidence: PCS. Frequency: 1/1. (PMID:29469822)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/18. (PMID:29469822)
- 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: 0/7. (PMID:30368668)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 13/23. (PMID:29469822;PMID:30368668)
- Nevus (HP:0003764): A nevus is a type of hamartoma that is a circumscribed stable malformation of the skin. Evidence: PCS. Frequency: 2/7. (PMID:30368668)
- 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: 9/15. (PMID:29469822;PMID:30368668)
- 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: 9/14. (PMID:29469822)
- Increased nuchal translucency (HP:0010880): Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy). Evidence: PCS. Frequency: 6/11. (PMID:29469822;PMID:30368668)
- Underdeveloped supraorbital ridges (HP:0009891): Flatness of the supraorbital portion of the frontal bones. Evidence: PCS. Frequency: 5/7. (PMID:30368668)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 8/27. (PMID:29469822;PMID:30368668)
- Abnormal sternum morphology (HP:0000766): An anomaly of the sternum, also known as the breastbone. Evidence: PCS. (PMID:29469822)
- 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:29469822)
- Eczematoid dermatitis (HP:0000964): Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces. Evidence: PCS. Frequency: 0/7. (PMID:30368668)
- 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: PCS. Frequency: 1/7. (PMID:30368668)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: PCS. Frequency: 3/27. (PMID:29469822;PMID:30368668)
- 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:30368668)
- 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: 20/23. (PMID:29469822;PMID:30368668)
- Hyperkeratosis (HP:0000962): Hyperkeratosis is a histopathological term defining a thickened stratum corneum and may be present in many different skin conditions, with many possible overlaps. Hyperkeratosis refers to the increased thickness of the stratum corneum, the outer layer of the skin. Hyperkeratosis is subclassified as orthokeratotic or parakeratotic. Orthokeratotic hyperkeratosis refers to the thickening of the keratin layer with preserved keratinocyte maturation, while parakeratotic hyperkeratosis shows retained nuclei as a sign of delayed maturation of keratinocytes. Evidence: PCS. Frequency: 4/7. (PMID:30368668)
- 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: 4/26. (PMID:29469822;PMID:30368668)
- Hypermelanotic macule (HP:0001034): A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size. Evidence: PCS. Frequency: 1/1. (PMID:29469822)
- 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: 4/7. (PMID:30368668)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/18. (PMID:29469822)
- 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: 4/20. (PMID:29469822)
- 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: 3/20. (PMID:29469822)
- Antenatal onset (HP:0030674): Onset prior to birth. Evidence: PCS. Frequency: 11/18. (PMID:29469822)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 10/20. (PMID:29469822)
- Nonimmune hydrops fetalis (HP:0001790): A type of hydrops fetalis in which there is no identifiable circulating antibody to red blood cell antigens . Evidence: PCS. Frequency: 2/24. (PMID:29469822;PMID:30368668)
- Abnormal coronary artery origin (HP:0011636): Isolated abnormalities of the coronary artery origins. This may be in associated with other structural heart malformations but not the patterns of complex structural heart malformations which result in abnormal course of the coronary arteries. Evidence: PCS. Frequency: 1/6. (PMID:30368668)
- Leukemia (HP:0001909): A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes. Evidence: PCS. Frequency: 2/20. (PMID:29469822)
- 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: 6/27. (PMID:29469822;PMID:30368668)
- Atrioventricular canal defect (HP:0006695): A defect of the atrioventricular septum of the heart. Evidence: PCS. Frequency: 1/20. (PMID:29469822)
- 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: 5/26. (PMID:29469822;PMID:30368668)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 3/20. (PMID:29469822)
- Redundant neck skin (HP:0005989): Excess skin around the neck, often lying in horizontal folds. Evidence: PCS. Frequency: 5/6. (PMID:29469822)
- Hyperextensible skin (HP:0000974): A condition in which the skin can be stretched beyond normal, and then returns to its initial position. Evidence: PCS. Frequency: 2/7. (PMID:30368668)
- Pulmonary artery stenosis (HP:0004415): An abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches. Evidence: PCS. Frequency: 1/1. (PMID:29469822)
- Curly hair (HP:0002212). Evidence: PCS. Frequency: 8/21. (PMID:29469822;PMID:30368668)
- 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: 3/20. (PMID:29469822)
- 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: 1/20. (PMID:29469822)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 6/20. (PMID:29469822)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/7. (PMID:30368668)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 2/20. (PMID:29469822)
- Fetal pleural effusion (HP:0025676): Fetal pleural effusion is the accumulation of excess fluid in the layers of tissue (pleura) lining the lungs and wall of the chest. It may be primary, also termed hydrothorax, occurring as an isolated finding or it may be secondary, most commonly resulting from non-immune hydrops. Evidence: PCS. Frequency: 1/4. (PMID:30368668)
- Distal arthrogryposis (HP:0005684): An inherited primary limb malformation disorder characterized by congenital contractures of two or more different body areas and without primary neurologic and/or muscle disease that affects limb function. Evidence: PCS. Frequency: 1/20. (PMID:29469822)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: IEA. (OMIM:605275)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 12/27. (PMID:29469822;PMID:30368668)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 4/20. (PMID:29469822)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: PCS. Frequency: 19/25. (PMID:29469822;PMID:30368668)
- 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: 2/20. (PMID:29469822)
- Mitral stenosis (HP:0001718): An abnormal narrowing of the orifice of the mitral valve. Evidence: IEA. (OMIM:605275)
- 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: 10/26. (PMID:29469822;PMID:30368668)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: PCS. Frequency: 2/20. (PMID:29469822)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: PCS. (PMID:29469822)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 2/20. (PMID:29469822)
- Cubitus valgus (HP:0002967): Abnormal positioning in which the elbows are turned out. Evidence: PCS. Frequency: 2/6. (PMID:30368668)
- Acute lymphoblastic leukemia (HP:0006721): A form of acute leukemia characterized by excess lympoblasts. Evidence: PCS. Frequency: 3/20. (PMID:29469822)
- 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: 7/8. (PMID:29469822;PMID:30368668)
- Webbed neck (HP:0000465): Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline. Evidence: PCS. Frequency: 7/10. (PMID:29469822;PMID:30368668)
- 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: 4/11. (PMID:29469822;PMID:30368668)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 9/13. (PMID:29469822)
- Mitral valve prolapse (HP:0001634): One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle. Evidence: PCS. Frequency: 1/1. (PMID:29469822)
These phenotypes are associated with the disease Noonan syndrome 2 (OMIM:605275).