Phenotypes associated with the disease cardiac, facial, and digital anomalies with developmental delay (OMIM:618164):
- 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: 25/49. (PMID:29961569;PMID:32376980)
- Aortic valve stenosis (HP:0001650): The presence of a stenosis (narrowing) of the aortic valve. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Decreased body weight (HP:0004325): Abnormally low body weight. Evidence: PCS. Frequency: 5/42. (PMID:32376980)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 26/49. (PMID:29961569;PMID:32376980)
- Tethered cord (HP:0002144): During normal embryological development, the spinal cord first occupies the entire length of the vertebral column but goes on to assume a position at the level of L1 due to differential growth of the conus medullaris and the vertebral column. The filum terminale is a slender, threadlike structure that remains after the normal regression of the distal embryonic spinal cord and attaches the spinal cord to the coccyx. A tethered cord results if there is a thickened rope-like filum terminale which anchors the cord at the level of L2 or below, potentially causing neurologic signs owing to abnormal tension on the spinal cord. Evidence: PCS. Frequency: 3/7. (PMID:29961569)
- 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: 10/42. (PMID:32376980)
- 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: 12/42. (PMID:32376980)
- 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: 9/49. (PMID:29961569;PMID:32376980)
- 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: 19/49. (PMID:29961569;PMID:32376980)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Ulnar deviation of finger (HP:0009465): Bending or curvature of a finger toward the ulnar side (i.e., away from the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly. Evidence: PCS. Frequency: 4/42. (PMID:32376980)
- 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: 17/42. (PMID:32376980)
- Overlapping toe (HP:0001845): Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent. Evidence: PCS. Frequency: 10/42. (PMID:32376980)
- 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: 6/42. (PMID:32376980)
- Radial deviation of finger (HP:0009466): Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly. Evidence: PCS. Frequency: 6/42. (PMID:32376980)
- Long hallux (HP:0001847): Increased length of the big toe. Evidence: PCS. Frequency: 4/42. (PMID:32376980)
- 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: 28/49. (PMID:29961569;PMID:32376980)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: PCS. Frequency: 2/7. (PMID:29961569)
- 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: 10/42. (PMID:32376980)
- 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: 23/42. (PMID:32376980)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- 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: PCS. Frequency: 1/42. (PMID:32376980)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/42. (PMID:32376980)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: PCS. Frequency: 4/42. (PMID:32376980)
- 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: 27/49. (PMID:29961569;PMID:32376980)
- 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: 4/42. (PMID:32376980)
- 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:29961569)
- Supravalvar pulmonary stenosis (HP:0034349): A cardiovascular malformation associated with narrowing at the level of the pulmonary sinotubular junction above the pulmonic valve. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Joint contracture (HP:0034392): A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part. Evidence: PCS. Frequency: 8/42. (PMID:32376980)
- 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: 6/42. (PMID:32376980)
- 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: PCS. Frequency: 6/49. (PMID:29961569;PMID:32376980)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 2/7. (PMID:29961569)
- 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: 17/42. (PMID:32376980)
- Sandal gap (HP:0001852): A widely spaced gap between the first toe (the great toe) and the second toe. Evidence: PCS. Frequency: 5/42. (PMID:32376980)
- 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:29961569)
- 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: 2/7. (PMID:29961569)
- 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: 2/7. (PMID:29961569)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 5/7. (PMID:29961569)
- 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: 7/42. (PMID:32376980)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 7/42. (PMID:32376980)
- Single umbilical artery (HP:0001195): Single umbilical artery (SUA) is the absence of one of the two umbilical arteries surrounding the fetal bladder and in the fetal umbilical cord. Evidence: PCS. Frequency: 2/7. (PMID:29961569)
- Blepharophimosis (HP:0000581): A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. Evidence: PCS. Frequency: 33/42. (PMID:32376980)
- Hypoplastic left ventricle (HP:0004383): A severe congenital heart defect characterized by underdevelopment of the left ventricle. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Pedal edema (HP:0010741): An abnormal accumulation of excess fluid in the lower extremity resulting in swelling of the feet and extending upward to the lower leg. Evidence: PCS. Frequency: 3/42. (PMID:32376980)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 34/47. (PMID:29961569;PMID:32376980)
- 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: 6/42. (PMID:32376980)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 4/42. (PMID:32376980)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Mitral atresia (HP:0011560): A congenital defect with failure to open of the mitral valve orifice. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 17/42. (PMID:32376980)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/7. (PMID:29961569)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: PCS. Frequency: 3/7. (PMID:29961569)
- Pulmonary artery atresia (HP:0004935): A congenital anomaly with a narrowing or complete absence of the opening between the right ventricle and the pulmonary artery. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 5/7. (PMID:29961569)
- Redundant neck skin (HP:0005989): Excess skin around the neck, often lying in horizontal folds. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- 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: 5/42. (PMID:32376980)
- Premature birth (HP:0001622): The birth of a baby of less than 37 weeks of gestational age. Evidence: PCS. Frequency: 10/42. (PMID:32376980)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- 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: 3/42. (PMID:32376980)
- 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: 33/47. (PMID:29961569;PMID:32376980)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 7/42. (PMID:32376980)
- Thickened nuchal skin fold (HP:0000474): A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome. Evidence: PCS. Frequency: 5/7. (PMID:29961569)
- Abnormal number of hair whorls (HP:0010813): More than two clockwise hair whorls. Evidence: PCS. Frequency: 3/7. (PMID:29961569)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 24/42. (PMID:32376980)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: PCS. Frequency: 6/42. (PMID:32376980)
- Keratosis pilaris (HP:0032152): An anomaly of the hair follicles of the skin that typically presents as small, rough, brown folliculocentric papules distributed over characteristic areas of the skin, particularly the outer-upper arms and thighs. Evidence: PCS. Frequency: 3/42. (PMID:32376980)
- 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: PCS. Frequency: 14/42. (PMID:32376980)
- Double outlet right ventricle (HP:0001719): Double outlet right ventricle (DORV) is a type of ventriculoarterial connection in which both great vessels arise entirely or predominantly from the right ventricle. Evidence: PCS. Frequency: 2/7. (PMID:29961569)
- 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: 23/49. (PMID:29961569;PMID:32376980)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/7. (PMID:29961569)
- 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: PCS. Frequency: 5/42. (PMID:32376980)
- 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: 9/42. (PMID:32376980)
- Neonatal respiratory distress (HP:0002643): Respiratory difficulty as newborn. Evidence: PCS. Frequency: 4/7. (PMID:29961569)