Phenotypes associated with the disease Cornelia de Lange syndrome 4 (OMIM:614701):
- Velopharyngeal insufficiency (HP:0000220): Inability of velopharyngeal sphincter to sufficiently separate the nasal cavity from the oral cavity during speech. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/2. (PMID:22633399)
- 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: 4/6. (PMID:31334757;PMID:22633399;PMID:32696056)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: TAS. (OMIM:614701)
- 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: 2/5. (PMID:31334757;PMID:22633399)
- Stapes ankylosis (HP:0000381): Stapes ankylosis refers to congenital or acquired fixation of the stapes (the stirrup-shaped small bone or ossicle in the middle ear), which is associated with conductive hearing resulting from impairment of the sound-conduction mechanism (the external auditory canal, tympanic membrane, and/or middle-ear ossicles). Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/3. (PMID:31334757)
- 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: 1/3. (PMID:31334757)
- 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: 2/5. (PMID:31334757;PMID:22633399)
- Enamel agenesis (HP:0033785): Complete or almost complete absence of enamel. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- Flat face (HP:0012368): Absence of concavity or convexity of the face when viewed in profile. Evidence: PCS. Frequency: 1/1. (PMID:32696056)
- Short femoral neck (HP:0100864): An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft). Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 2/3. (PMID:22633399;PMID:32696056)
- Hemivertebrae (HP:0002937): Absence of one half of the vertebral body. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614701)
- 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: 1/1. (PMID:32696056)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/3. (PMID:31334757)
- Lobar holoprosencephaly (HP:0006870): A type of holoprosencephaly in which most of the right and left cerebral hemispheres and lateral ventricles are separated but the most rostral aspect of the telencephalon, the frontal lobes, are fused, especially ventrally. Evidence: PCS. Frequency: 1/1. (PMID:32696056)
- 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: 2/2. (PMID:22633399)
- Coxa vara (HP:0002812): Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/1. (PMID:32696056)
- Skull asymmetry (HP:0002678). Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- Radioulnar synostosis (HP:0002974): An abnormal osseous union (fusion) between the radius and the ulna. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/2. (PMID:22633399)
- 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: 2/5. (PMID:31334757;PMID:22633399)
- 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. Frequency: Occasional (HP:0040283). (OMIM:614701)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 4/4. (PMID:31334757;PMID:22633399)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 3/5. (PMID:31334757;PMID:22633399)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 3/3. (PMID:22633399;PMID:32696056)
- 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: 2/4. (PMID:31334757;PMID:32696056)
- 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: 5/5. (PMID:31334757;PMID:22633399)
- 2-3 toe syndactyly (HP:0004691): Syndactyly with fusion of toes two and three. Evidence: PCS. Frequency: 2/2. (PMID:22633399)
- Exostoses (HP:0100777): An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage. Evidence: TAS. (OMIM:614701)
- Cutis marmorata (HP:0000965): A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/2. (PMID:22633399)
- 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: 2/4. (PMID:31334757;PMID:32696056)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 2/5. (PMID:31334757;PMID:22633399)
- 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: 1/2. (PMID:22633399)
- Syndactyly (HP:0001159): Webbing or fusion of the fingers or 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 fingers or toes in a proximo-distal axis are referred to as "symphalangism". Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614701)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 3/5. (PMID:31334757;PMID:22633399)
- 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:22633399)
- Vertebral clefting (HP:0008428): Schisis (cleft or cleavage) of vertebral bodies. Evidence: PCS. Frequency: 1/2. (PMID:22633399)
- 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: PCS. Frequency: 1/2. (PMID:22633399)
- 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: 1/3. (PMID:31334757)
- 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:31334757)