- 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: 1/1. (PMID:16596670)
- Dermal translucency (HP:0010648): An abnormally increased ability of the skin to permit light to pass through (translucency) such that subcutaneous structures such as veins display an increased degree of visibility. Evidence: PCS. Frequency: 11/34. (PMID:15731757;PMID:16928994)
- Eosinophilic infiltration of the esophagus (HP:0410151): Infiltration of numerous eosinophils (usually greater than 15 per high power field) into the squamous epithelium of the esophagus, and layering of eosinophils on the surface layer of the esophagus. Evidence: PCS. (PMID:23608731)
- Cervical spine instability (HP:0010646): An abnormal lack of stability of the cervical spine. Evidence: PCS. Frequency: 7/30. (PMID:16928994)
- Chronic fatigue (HP:0012432): Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer. Evidence: PCS. Frequency: 1/1. (PMID:16596670)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: PCS. Frequency: 39/40. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:16928994;PMID:31475485)
- 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: 1/8. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
- 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: 31/37. (PMID:15731757;PMID:16596670;PMID:16928994)
- Descending thoracic aorta aneurysm (HP:0004959): An abnormal localized widening (dilatation) of the descending thoracic aorta. Evidence: PCS. Frequency: 0/5. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
- 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: 6/34. (PMID:15731757;PMID:16928994)
- 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: 2/4. Onset: Neonatal onset (HP:0003623). (PMID:15731757)
- 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: 10/30. Onset: Neonatal onset (HP:0003623). (PMID:16928994)
- 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:31475485)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 2/2. (PMID:16596670)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 19/39. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:16928994;PMID:31475485)
- 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. (PMID:16928994)
- 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: 2/9. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 1/2. (PMID:16596670)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: PCS. Frequency: 1/2. (PMID:16596670)
- 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: 25/37. (PMID:15731757;PMID:16596670;PMID:16928994)
- 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: 4/36. (PMID:29706644;PMID:15731757;PMID:16928994)
- Striae distensae (HP:0001065): Thinned, erythematous, depressed bands of atrophic skin. Initially, striae appear as flattened and thinned, pinkish linear regions of the skin. Striae tend to enlarge in length and become reddish or purplish. Later, striae tend to appear as white, depressed bands that are parallel to the lines of skin tension. Striae distensae occur most often in areas that have been subject to distension such as the lower back, buttocks, thighs, breast, abdomen, and shoulders. Evidence: PCS. Frequency: 1/1. (PMID:29706644)
- Bicuspid pulmonary valve (HP:0005182): The presence of a bicuspid pulmonary valve. Evidence: PCS. Frequency: 0/7. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
- Dilatation of the ductus arteriosus (HP:0030745): Ductus arteriosus aneurysm (DAA) is a saccular dilatation of the ductus arteriosus. DAA can be either congenital or acquired (e.g. as a complication of surgical closure of a patent ductus arteriosus). Although the majority of patients with congenital DAA are asymptomatic and have a benign course, severe complications, such as rupture or thromboembolism, can occur. DAA is likely to emerge in the third trimester from the aortic junction of the DA, extending towards its pulmonary end. Evidence: PCS. Frequency: 0/3. (PMID:15731757)
- 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: 12/36. (PMID:15731757;PMID:16928994;PMID:31475485)
- Postaxial polydactyly (HP:0100259): A form of polydactyly in which the extra digit or digits are localized on the side of the fifth finger or fifth toe. Evidence: PCS. Frequency: 0/6. (PMID:29706644;PMID:15731757)
- Dural ectasia (HP:0100775): A widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level. Evidence: PCS. Frequency: 1/1. (PMID:31475485)
- Chiari malformation (HP:0002308): Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow. Evidence: PCS. Frequency: 4/34. (PMID:15731757;PMID:16928994)
- 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: 1/1. (PMID:29706644)
- Abnormal sternum morphology (HP:0000766): An anomaly of the sternum, also known as the breastbone. Evidence: PCS. Frequency: 24/35. (PMID:15731757;PMID:16928994)
- 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: 2/5. (PMID:29706644;PMID:15731757;PMID:16596670)
- Supernumerary ribs (HP:0005815): The presence of more than 12 rib pairs. Evidence: PCS. Frequency: 1/1. (PMID:16596670)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: PCS. Frequency: 6/15. (PMID:15731757;PMID:16596670;PMID:16928994)
- 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:16928994)
- 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: 1/3. (PMID:16596670;PMID:31475485)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 1/1. (PMID:16596670)
- Arterial tortuosity (HP:0005116): Abnormal tortuous (i.e., twisted) form of arteries. Evidence: PCS. Frequency: 16/35. (PMID:29706644;PMID:15731757;PMID:16928994)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/2. (PMID:16596670)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 2/2. (PMID:16596670)
- Hypoplasia of the musculature (HP:0009004): Underdevelopment of the musculature. Evidence: PCS. Frequency: 1/1. (PMID:16596670)
- Pulmonary artery aneurysm (HP:0004937): An aneurysm (severe localized balloon-like outward bulging) in the pulmonary artery. Evidence: PCS. Frequency: 5/8. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
- 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: 3/4. (PMID:29706644;PMID:16596670;PMID:31475485)
- Soft skin (HP:0000977): Subjective impression of increased softness upon palpation of the skin. Evidence: PCS. Frequency: 12/35. (PMID:15731757;PMID:16596670;PMID:16928994)
- 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: 2/3. (PMID:16596670;PMID:31475485)
- Ascending aortic dissection (HP:0004933): A separation of the layers within the wall of the ascending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space. Evidence: PCS. Frequency: 6/14. (PMID:29706644;PMID:16596670;PMID:16928994;PMID:31475485)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 2/4. (PMID:15731757)
- Arachnodactyly (HP:0001166): Abnormally long and slender fingers (spider fingers). Evidence: PCS. Frequency: 25/36. (PMID:15731757;PMID:16596670;PMID:16928994)
- 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: 18/37. (PMID:15731757;PMID:16596670;PMID:16928994;PMID:31475485)
- Spondylolisthesis (HP:0003302): Complete bilateral fractures of the pars interarticularis resulting in the anterior slippage of the vertebra. Evidence: PCS. Frequency: 1/2. (PMID:16596670)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 21/38. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:16928994)
- Talipes equinovarus (HP:0001762): Talipes equinovarus (also called clubfoot) typically has four main components: inversion and adduction of the forefoot; inversion of the heel and hindfoot; equinus (limitation of extension) of the ankle and subtalar joint; and internal rotation of the leg. Evidence: PCS. Frequency: 16/35. (PMID:15731757;PMID:16928994)
- Postaxial hand polydactyly (HP:0001162): Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger). Evidence: PCS. (PMID:16928994)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: PCS. Frequency: 30/34. (PMID:15731757;PMID:16928994;PMID:31475485)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: PCS. Frequency: 1/1. (PMID:31475485)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: PCS. Frequency: 14/36. (PMID:15731757;PMID:16596670;PMID:16928994)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: PCS. Frequency: 23/38. (PMID:15731757;PMID:16596670;PMID:16928994;PMID:31475485)
- Self-healing squamous epithelioma (HP:0034720): A type of skin tumor that initially presents as a reddish macule and subsequently becomes papular, enlarged, ulcerated and ultimately heals leaving pitted scars. Evidence: PCS. Frequency: 0/7. (PMID:29706644;PMID:15731757)
- Ectopia lentis (HP:0001083): Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation. Evidence: PCS. Frequency: 0/32. (PMID:29706644;PMID:16596670;PMID:16928994)
- Disproportionate tall stature (HP:0001519): A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim. Evidence: PCS. Frequency: 7/35. (PMID:15731757;PMID:16928994)
- 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: 1/2. (PMID:16596670)
- 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: 1/3. Onset: Congenital onset (HP:0003577). (PMID:15731757)
- 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: 5/30. (PMID:16928994)
- 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: 0/1. (PMID:29706644)
- 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: 0/1. (PMID:16596670)
- 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: 0/1. (PMID:31475485)
- Dilatation of the cerebral artery (HP:0004944): The presence of a localized dilatation or ballooning of a cerebral artery. Evidence: IEA. (OMIM:609192)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 11/13. (PMID:16596670;PMID:16928994;PMID:31475485)
- 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: 2/8. (PMID:29706644;PMID:15731757;PMID:16596670;PMID:31475485)
These phenotypes are associated with the disease Loeys-Dietz syndrome 1 (OMIM:609192).