- 3-4 finger cutaneous syndactyly (HP:0011939): A soft tissue continuity in the A/P axis between fingers 3 and 4. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- 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: 2/5. (PMID:32041641)
- 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: 4/8. (PMID:25728775)
- 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: 1/4. (PMID:25728775)
- Bronchomalacia (HP:0002780): Weakness or softness of the cartilage in the walls of the bronchial tubes. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- 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: 3/4. (PMID:25728775)
- Gait imbalance (HP:0002141). Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Deviation of the hallux (HP:0010051): Displacement of the big toe from its normal position. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- 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: TAS. (OMIM:616268)
- 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: 5/5. (PMID:32041641)
- Recurrent urinary tract infections (HP:0000010): Repeated infections of the urinary tract. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 7/9. (PMID:25728775;PMID:32041641)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- 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: 3/5. (PMID:32041641)
- Enlarged proximal interphalangeal joints (HP:0006185). Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Peg-shaped maxillary lateral incisors (HP:0006342): A tooth crown with its mesial and distal sides converging or tapering toward the incisal edge causing severe reduction of mesiodistal diameter. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- 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: 1/5. (PMID:32041641)
- Amblyopia (HP:0000646): Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Long thorax (HP:0100818): Increased inferior to superior extent of the thorax. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- 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: 1/2. (PMID:25728775)
- Sandal gap (HP:0001852): A widely spaced gap between the first toe (the great toe) and the second toe. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Lacrimal duct stenosis (HP:0007678): Narrowing of a tear duct (lacrimal duct). Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- 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: 4/5. (PMID:32041641)
- 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:32041641)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- 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: TAS. (OMIM:616268)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 4/4. (PMID:25728775)
- 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: 1/4. (PMID:25728775)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Upper eyelid edema (HP:0012724): Edema in the region of the upper eyelid. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- Insomnia (HP:0100785): Persistent difficulty in starting or maintaining sleep, or waking up earlier than desired, despite having adequate opportunities and conditions for sleep. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Prominent antitragus (HP:0008593): Increased anterosuperior prominence of the area between the bottom of the incisura and the inner margin of the antihelix. Evidence: PCS. Frequency: 3/5. (PMID:32041641)
- 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: TAS. (OMIM:616268)
- 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: 4/5. (PMID:32041641)
- 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: TAS. (OMIM:616268)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- Prominent umbilicus (HP:0001544): Abnormally prominent umbilicus (belly button). Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. Frequency: 4/5. (PMID:32041641)
- Bifid nasal tip (HP:0000456): A splitting of the nasal tip. Visually assessable vertical indentation, cleft, or depression of the nasal tip. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Secundum atrial septal defect (HP:0001684): A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Respiratory distress (HP:0002098): Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea. Evidence: PCS. Frequency: 1/5. Onset: Neonatal onset (HP:0003623). (PMID:32041641)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: PCS. Frequency: 1/4. (PMID:32041641)
- Conjunctivitis (HP:0000509): Inflammation of the conjunctiva. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- 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: 2/4. (PMID:25728775)
- Lower limb asymmetry (HP:0100559): A difference in length or diameter between the left and right leg. Evidence: PCS. Frequency: 1/4. (PMID:32041641)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: TAS. (OMIM:616268)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Webbed neck (HP:0000465): Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline. Evidence: PCS. Frequency: 0/5. (PMID:32041641)
- Neonatal respiratory distress (HP:0002643): Respiratory difficulty as newborn. Evidence: TAS. (OMIM:616268)
- 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: 5/9. (PMID:25728775;PMID:32041641)
- Recurrent aspiration pneumonia (HP:0002100): Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- 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: 3/5. (PMID:32041641)
- 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: 2/5. (PMID:32041641)
- 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: 3/4. (PMID:25728775)
- Thin eyebrow (HP:0045074): Decreased diameter of eyebrow hairs. Evidence: PCS. Frequency: 3/5. (PMID:32041641)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 4/5. (PMID:32041641)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: PCS. Frequency: 4/4. (PMID:25728775)
- 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: TAS. (OMIM:616268)
- Pulmonic stenosis (HP:0001642): A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis). Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- 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: 4/5. (PMID:32041641)
- 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: 5/5. (PMID:32041641)
- Hammertoe (HP:0001765): Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- 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:25728775)
- 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: 3/4. (PMID:25728775)
- 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: 7/9. (PMID:25728775;PMID:32041641)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 4/4. (PMID:25728775)
- 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: 4/8. (PMID:25728775;PMID:32041641)
- Sparse medial eyebrow (HP:0025325): Decreased density/number and/or decreased diameter of medial eyebrow hairs. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- Protuberant abdomen (HP:0001538): A thrusting or bulging out of the abdomen. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 2/4. (PMID:25728775)
- 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: 2/5. (PMID:32041641)
- Bilateral cryptorchidism (HP:0008689): Absence of 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: 1/2. (PMID:25728775)
- 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: 4/5. (PMID:32041641)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Small earlobe (HP:0000385): Reduced volume of the earlobe. Evidence: PCS. Frequency: 3/5. (PMID:32041641)
- Low-set nipples (HP:0002562): Placement of the nipples at a lower than normal location. Evidence: PCS. Frequency: 3/4. (PMID:32041641)
- Short hallux (HP:0010109): Underdevelopment (hypoplasia) of the big toe. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Anteverted ears (HP:0040080). Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- 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: 1/3. (PMID:25728775)
- Low hanging columella (HP:0009765): Columella extending inferior to the level of the nasal base, when viewed from the side. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- Lower limb hypertonia (HP:0006895). Evidence: PCS. Frequency: 3/5. (PMID:32041641)
- Downturned corners of mouth (HP:0002714): A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure. Evidence: TAS. (OMIM:616268)
- Narrow chest (HP:0000774): Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- Upper limb amyotrophy (HP:0009129): Muscular atrophy involving the muscles of the upper limbs. Evidence: PCS. Frequency: 4/5. (PMID:32041641)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Prominent antihelix (HP:0000395): The presence of an abnormally prominent antihelix. Evidence: PCS. Frequency: 5/5. (PMID:32041641)
- 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: TAS. (OMIM:616268)
- 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: 4/5. (PMID:32041641)
- Genu varum (HP:0002970): A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together. Evidence: PCS. Frequency: 1/5. (PMID:32041641)
- 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: 4/4. (PMID:25728775)
- Freckling (HP:0001480): The presence of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Underdeveloped tragus (HP:0011272): Decreased posterolateral protrusion of the tragus. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: TAS. (OMIM:616268)
- Lower limb amyotrophy (HP:0007210): Muscular atrophy affecting the lower limb. Evidence: PCS. Frequency: 4/5. (PMID:32041641)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 4/13. (PMID:25728775;PMID:32041641)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 3/5. (PMID:32041641)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: TAS. (OMIM:616268)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/5. Onset: Antenatal onset (HP:0030674). (PMID:32041641)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Chronic otitis media (HP:0000389): Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 1/4. (PMID:25728775)
- 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: 4/8. (PMID:25728775;PMID:32041641)
- 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: 2/5. (PMID:32041641)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: PCS. Frequency: 2/5. (PMID:32041641)
- 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: 1/4. (PMID:25728775)
These phenotypes are associated with the disease autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (OMIM:616268).