Phenotypes associated with the disease CTCF-related neurodevelopmental disorder (OMIM:615502):
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 10/42. (PMID:31239556)
- 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: 1/46. (PMID:31239556)
- 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: 2/4. (PMID:23746550)
- 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: 1/45. (PMID:31239556)
- 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: 1/4. (PMID:23746550)
- Acetabular dysplasia (HP:0008807): A smaller than normal acetabulum that has insufficient femoral head coverage leading to abnormal hip joint contact pressures, instability and pain. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 4/46. (PMID:31239556)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 1/26. (PMID:31239556)
- Long palpebral fissure (HP:0000637): Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Proximal placement of thumb (HP:0009623): Proximal mislocalization of the thumb. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Broad palm (HP:0001169): For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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: 2/50. (PMID:31239556;PMID:23746550)
- 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: 3/46. (PMID:31239556)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 3/46. (PMID:31239556)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 21/45. (PMID:31239556;PMID:23746550)
- 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: 3/46. (PMID:31239556)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Finger syndactyly (HP:0006101): Webbing or fusion of the fingers, 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 in a proximo-distal axis are referred to as "Symphalangism". Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 6/50. (PMID:31239556;PMID:23746550)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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:23746550)
- 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: 4/46. (PMID:31239556)
- 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: 3/50. (PMID:31239556;PMID:23746550)
- 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:31239556)
- 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: 1/46. (PMID:31239556)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 4/4. (PMID:23746550)
- 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: 5/46. (PMID:31239556)
- 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: 7/50. (PMID:31239556;PMID:23746550)
- 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: 6/46. (PMID:31239556)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 1/25. (PMID:31239556)
- Blepharophimosis (HP:0000581): A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 9/31. (PMID:31239556)
- 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: 4/45. (PMID:31239556)
- Arachnoid cyst (HP:0100702): An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid. Evidence: PCS. Frequency: 4/25. (PMID:31239556)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: PCS. Frequency: 7/46. (PMID:31239556)
- 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: 2/46. (PMID:31239556)
- Periventricular leukomalacia (HP:0006970): Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 13/46. (PMID:31239556)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 6/29. (PMID:31239556;PMID:23746550)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Incisor macrodontia (HP:0011081): Increased size of the incisor tooth. Evidence: PCS. Frequency: 1/4. (PMID:23746550)
- Prominent supraorbital ridges (HP:0000336): Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 31/41. (PMID:31239556)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Thin vermilion border (HP:0000233): Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips). Evidence: PCS. Frequency: 9/9. (PMID:31239556;PMID:23746550)
- Open mouth (HP:0000194): A facial appearance characterized by a permanently or nearly permanently opened mouth. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Generalized tonic seizure (HP:0010818): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 1/4. (PMID:23746550)
- Bilateral tonic-clonic seizure with generalized onset (HP:0025190): A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 1/46. (PMID:31239556)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 2/50. (PMID:31239556;PMID:23746550)
- 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: 4/46. (PMID:31239556)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 4/4. (PMID:31239556)
- Short toe (HP:0001831): A toe that appears disproportionately short compared to the foot. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 8/50. (PMID:31239556;PMID:23746550)
- 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: 1/46. (PMID:31239556)
- 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: 7/50. (PMID:31239556;PMID:23746550)
- 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: 22/39. (PMID:31239556;PMID:23746550)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 1/45. (PMID:31239556)
- Spastic gait (HP:0002064): Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg. Evidence: PCS. Frequency: 2/45. (PMID:31239556)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Sparse eyebrow (HP:0045075): Decreased density/number of eyebrow hairs. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 2/46. (PMID:31239556)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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: 6/50. (PMID:31239556;PMID:23746550)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 5/50. (PMID:31239556;PMID:23746550)
- Broad foot (HP:0001769): A foot for which the measured width is above the 95th centile for age; or, a foot that appears disproportionately wide for its length. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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: 1/4. (PMID:23746550)
- 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: 3/46. (PMID:31239556)
- 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: 56/56. (PMID:31239556;PMID:23746550)
- 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: 1/4. (PMID:23746550)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 35/47. (PMID:31239556;PMID:23746550)
- 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: 2/46. (PMID:31239556)
- 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: 50/50. (PMID:31239556;PMID:23746550)
- Wide nasal base (HP:0012810): Increased distance between the attachments of the alae nasi to the face. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 2/46. (PMID:31239556)
- 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: 10/50. (PMID:31239556;PMID:23746550)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 1/46. (PMID:31239556)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: PCS. Frequency: 1/4. (PMID:23746550)
- Short philtrum (HP:0000322): Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 1/46. (PMID:31239556)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: PCS. Frequency: 3/4. (PMID:23746550)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 22/43. (PMID:31239556)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 19/45. (PMID:31239556;PMID:23746550)
- 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: 2/2. (PMID:31239556)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Microtia (HP:0008551): Underdevelopment of the external ear. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Hip subluxation (HP:0030043): A partial dislocation of the hip joint, whereby the head of the femur is partially displaced from the socket. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Ectropion (HP:0000656): An outward turning (eversion) or rotation of the eyelid margin. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Low hanging columella (HP:0009765): Columella extending inferior to the level of the nasal base, when viewed from the side. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Cupped ear (HP:0000378): Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura). Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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: 2/46. (PMID:31239556)
- Hypoplastic philtrum (HP:0005326): Underdevelopment of the philtrum. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- 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: 3/46. (PMID:31239556)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/25. (PMID:31239556)
- 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: 1/46. (PMID:31239556)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 3/46. (PMID:31239556)
- 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: 22/40. (PMID:31239556)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: PCS. Frequency: 1/45. (PMID:31239556)
- Narrow palpebral fissure (HP:0045025): Reduction in the vertical distance between the upper and lower eyelids. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Broad chin (HP:0011822): Increased width of the midpoint of the mandible (mental protuberance) and overlying soft tissue. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 2/46. (PMID:31239556)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: PCS. Frequency: 1/46. (PMID:31239556)
- 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: 7/10. (PMID:31239556;PMID:23746550)
- 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: 2/3. (PMID:23746550)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 5/46. (PMID:31239556)