Phenotypes associated with the disease Coffin-Siris syndrome 12 (OMIM:619325):
- 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: 7/12. (PMID:33232675)
- 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: 5/12. (PMID:33232675)
- 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: 3/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- 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: 4/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- 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: 12/12. (PMID:33232675)
- Simple ear (HP:0020206): The pinna has fewer folds and grooves than usual. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Large earlobe (HP:0009748): Increased volume of the earlobe, that is, abnormally prominent ear lobules. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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: 3/12. (PMID:33232675)
- Radioulnar synostosis (HP:0002974): An abnormal osseous union (fusion) between the radius and the ulna. Evidence: PCS. Frequency: 1/11. (PMID:33232675)
- Submucous cleft hard palate (HP:0000176): Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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: 3/12. (PMID:33232675)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 5/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- 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: 7/12. (PMID:33232675)
- 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: 3/12. (PMID:33232675)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Overfolding of the superior helices (HP:0004453): A condition in which the superior portion of the helix is folded over to a greater degree than normal. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- 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: 12/12. (PMID:33232675)
- 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: 3/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Noncommunicating hydrocephalus (HP:0010953): A form of hydrocephalus in which the flow of cerebrospinal fluid (CSF) within the cerebral ventricular system or in the outlets of the CSF to the arachnoid space is obstructed. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- High anterior hairline (HP:0009890): 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 above the mean. Alternatively, an apparently increased distance between the hairline and the glabella. Evidence: PCS. Frequency: 4/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- 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: 5/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 4/12. (PMID:33232675)
- 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: 1/8. (PMID:33232675)
- Short thumb (HP:0009778): Hypoplasia (congenital reduction in size) of the thumb. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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:33232675)
- 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: 4/12. (PMID:33232675)
- Oral motor hypotonia (HP:0030190): Reduced muscle tone of oral musculature. In infants, this feature may be associated with difficulties in breast feeding, and may affect the latch, jaw motions, tongue placement, lip seal, suck/swallow/breathe pattern and overall feeding behavior. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- 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: 4/12. (PMID:33232675)
- Velopharyngeal insufficiency (HP:0000220): Inability of velopharyngeal sphincter to sufficiently separate the nasal cavity from the oral cavity during speech. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Facial palsy (HP:0010628): Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Small nail (HP:0001792): A nail that is diminished in length and width, i.e., underdeveloped nail. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- 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: 3/11. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Prominent nasal tip (HP:0005274). Evidence: PCS. Frequency: 7/12. (PMID:33232675)
- Hippocampal atrophy (HP:0410170): Partial or complete wasting (loss) of hippocampus tissue that was once present. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Cutaneous syndactyly (HP:0012725): A soft tissue continuity in the A/P axis between two digits that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two digits that lies significantly distal to the flexion crease that overlies the metacarpophalangeal or metatarsophalangeal joint of the adjacent digits. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Ridged cranial sutures (HP:0010823): An overlap of the bony plates of the skull in an infant, with or without early closure. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 5/12. (PMID:33232675)
- 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: 4/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 5/12. (PMID:33232675)
- Low hanging columella (HP:0009765): Columella extending inferior to the level of the nasal base, when viewed from the side. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- 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: 5/12. (PMID:33232675)
- 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: 2/12. (PMID:33232675)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Prominent antihelix (HP:0000395): The presence of an abnormally prominent antihelix. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/11. (PMID:33232675)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Prominent glabella (HP:0002057): Forward protrusion of the glabella. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- 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: PCS. Frequency: 1/12. (PMID:33232675)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Narrow palpebral fissure (HP:0045025): Reduction in the vertical distance between the upper and lower eyelids. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Broad thumb (HP:0011304): Increased thumb width without increased dorso-ventral dimension. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: PCS. Frequency: 5/12. (PMID:33232675)
- Celiac disease (HP:0002608): Celiac disease (CD) is an autoimmune condition affecting the small intestine, triggered by the ingestion of gluten, the protein fraction of wheat, barley, and rye. Clinical manifestations of CD are highly variable and include both gastrointestinal and non-gastrointestinal features. The hallmark of CD is an immune-mediated enteropathy. This term is included because the occurrence of CD is seen as a feature of a number of other diseases. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- 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: 1/12. (PMID:33232675)
- Sparse scalp hair (HP:0002209): Decreased number of hairs per unit area of skin of the scalp. Evidence: PCS. Frequency: 2/12. (PMID:33232675)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 5/12. (PMID:33232675)
- Enlarged cerebellum (HP:0012081): An abnormally increased size of the cerebellum compared to other brain structures. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: PCS. Frequency: 1/12. (PMID:33232675)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 4/12. (PMID:33232675)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 4/12. (PMID:33232675)
- 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: 1/8. (PMID:33232675)
- 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: 1/11. (PMID:33232675)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 3/12. (PMID:33232675)
- Slender finger (HP:0001238): Fingers that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual. Evidence: PCS. Frequency: 1/12. (PMID:33232675)