- Thoracic lordosis (HP:0430043): Thoracic lordosis refers to an abnormal curvature of the thoracic spine in which the thoracic spine displays lordosis (inward curve) instead of the normal kyphosis (outward curve). Evidence: PCS. Frequency: 3/3. (PMID:30195269)
- Astigmatism (HP:0000483): A type of refraction error associated with abnormal curvatures on the anterior and/or posterior surface of the cornea. Evidence: PCS. Frequency: 4/6. (PMID:20503305)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 4/6. (PMID:20503305)
- 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: 5/6. (PMID:20503305)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: PCS. Frequency: 4/4. Onset: Infantile onset (HP:0003593). (PMID:20503305)
- 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: TAS. (OMIM:601776)
- Joint dislocation (HP:0001373): Displacement or malalignment of joints. Evidence: PCS. Frequency: 4/6. (PMID:20503305)
- Microcornea (HP:0000482): A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood. Evidence: TAS. (OMIM:601776)
- 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: 5/5. (PMID:20503305)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:601776)
- 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: 6/6. (PMID:20503305)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Frequency: 5/5. (PMID:20503305)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: PCS. Frequency: 5/6. (PMID:20503305)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:601776)
- 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: IEA. (OMIM:601776)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 3/6. (PMID:20503305)
- Diastasis recti (HP:0001540): A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba). Evidence: TAS. (OMIM:601776)
- 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: TAS. (OMIM:601776)
- 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: TAS. (OMIM:601776)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: IEA. (OMIM:601776)
- 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. (PMID:26373698)
- 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: IEA. (OMIM:601776)
- Recurrent skin infections (HP:0001581): Infections of the skin that happen multiple times. Evidence: PCS. Frequency: 5/6. (PMID:20503305)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 5/5. (PMID:20503305)
- Adducted thumb (HP:0001181): In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger. Evidence: TAS. (OMIM:601776)
- Dysesthesia (HP:0012534): Painful sensations elicited by a nonpainful cutaneous stimulus such as a light touch or gentle stroking over affected areas of the body. Sometimes referred to as hyperpathia or hyperalgesia. Often perceived as an intense burning, dyesthesias may outlast the stimulus by several seconds. Evidence: PCS. (PMID:26373698)
- Tricuspid regurgitation (HP:0005180): Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium. Evidence: PCS. Frequency: 1/5. (PMID:20503305)
- Scarring (HP:0100699): A scar refers to a lesion in which wound, burn, or sore has not healed completely and fibrous connective tissue has developed. Evidence: TAS. (OMIM:601776)
- 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: 4/6. (PMID:20503305)
- Umbilical hernia (HP:0001537): Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect. Evidence: TAS. (OMIM:601776)
- 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:20004762)
- Aortic regurgitation (HP:0001659): An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle. Evidence: PCS. Frequency: 2/5. (PMID:20503305)
- Pneumothorax (HP:0002107): Accumulation of air in the pleural cavity leading to a partially or completely collapsed lung. Evidence: PCS. Frequency: 3/6. (PMID:20503305)
- Mitral regurgitation (HP:0001653): An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction. Evidence: PCS. Frequency: 2/5. (PMID:20503305)
- 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: TAS. (OMIM:601776)
- 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: 5/5. (PMID:20503305)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 5/5. Onset: Juvenile onset (HP:0003621). (PMID:20503305)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. (OMIM:601776)
- Abnormal duodenum morphology (HP:0002246): An abnormality of the duodenum, i.e., the first section of the small intestine. Evidence: TAS. (OMIM:601776)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 3/6. (PMID:20503305)
- 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: 5/5. (PMID:20503305)
- Retinal detachment (HP:0000541): Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Evidence: TAS. (OMIM:601776)
- Generalized joint hypermobility (HP:0002761): Joint hypermobility (ability of a joint to move beyond its normal range of motion) affecting many or all joints of the body. In individuals with Joint hypermobility at multiple sites (usually five or more), the term generalized joint hypermobility is preferred. Evidence: TAS. (OMIM:601776)
- Nephrotic syndrome (HP:0000100): Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia. Evidence: TAS. (OMIM:601776)
- Fragile skin (HP:0001030): Skin that splits easily with minimal injury. Evidence: TAS. (OMIM:601776)
- Short columella (HP:0002000): Reduced distance from the anterior border of the naris to the subnasale. Evidence: PCS. Frequency: 5/5. (PMID:20503305)
- Atrophic scars (HP:0001075): Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin. Evidence: PCS. Frequency: 5/6. (PMID:20503305)
- Ecchymosis (HP:0031364): A purpuric lesion that is larger than 1 cm in diameter. Evidence: IEA. (OMIM:601776)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. (OMIM:601776)
- 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: TAS. (OMIM:601776)
- Bruising susceptibility (HP:0000978): An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma. Evidence: PCS. Frequency: 6/6. (PMID:20503305)
- 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: 5/5. (PMID:20503305)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. (OMIM:601776)
- Tricuspid valve prolapse (HP:0001704): One or more of the leaflets (cusps) of the tricuspid valve bulges back into the right atrium upon contraction of the right ventricle. Evidence: PCS. Frequency: 1/5. (PMID:20503305)
- 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: 6/6. (PMID:20503305)
- 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: TAS. (OMIM:601776)
- 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: 6/6. (PMID:20503305)
- Arachnodactyly (HP:0001166): Abnormally long and slender fingers (spider fingers). Evidence: IEA. (OMIM:601776)
- Abnormal anterior chamber morphology (HP:0000593): Abnormality of the anterior chamber, which is the space in the eye that is behind the cornea and in front of the iris. Evidence: IEA. (OMIM:601776)
- Abnormality of the mouth (HP:0000153): An abnormality of the mouth. Evidence: IEA. (OMIM:601776)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 6/6. (PMID:20503305)
- 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. (PMID:20503305)
- Delayed cranial suture closure (HP:0000270): Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age. Evidence: IEA. (OMIM:601776)
- 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: TAS. Frequency: 20/20. (OMIM:601776)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: PCS. Frequency: 6/6. (PMID:20503305)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 4/4. Onset: Infantile onset (HP:0003593). (PMID:20503305)
- 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: IEA. (OMIM:601776)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: IEA. (OMIM:601776)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: TAS. (OMIM:601776)
- 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: 1/5. (PMID:20503305)
- 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: TAS. Frequency: Very frequent (HP:0040281). (OMIM:601776)
- Glaucoma (HP:0000501): Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure. Evidence: PCS. Frequency: 3/6. (PMID:20503305)
- Intestinal malrotation (HP:0002566): An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis. Evidence: TAS. (OMIM:601776)
- 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: 4/6. (PMID:20503305)
- 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: 1/5. (PMID:20503305)
- Flat forehead (HP:0004425): A forehead with abnormal flatness. Evidence: TAS. (OMIM:601776)
These phenotypes are associated with the disease Ehlers-Danlos syndrome, musculocontractural type 1 (OMIM:601776).