- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Increased nuchal translucency (HP:0010880): Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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). (ORPHA:453504)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Conductive hearing impairment (HP:0000405): An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Shallow orbits (HP:0000586): Reduced depth of the orbits associated with prominent-appearing ocular globes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Abnormal optic nerve morphology (HP:0000587): Abnormality of the optic nerve. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Coloboma (HP:0000589): A developmental defect characterized by a cleft of some portion of the eye or ocular adnexa. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Optic nerve hypoplasia (HP:0000609): Underdevelopment of the optic nerve. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Overgrowth (HP:0001548): Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Heat intolerance (HP:0002046): The inability to maintain a comfortable body temperature in warm or hot weather. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Exaggerated cupid's bow (HP:0002263): More pronounced paramedian peaks and median notch of the Cupid's bow. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Supernumerary nipple (HP:0002558): Presence of more than two nipples. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Gastroparesis (HP:0002578): Decreased strength of the muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Gastrointestinal dysmotility (HP:0002579): Abnormal intestinal contractions, such as spasms and intestinal paralysis, related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Nocturnal hypoventilation (HP:0002877): An abnormal reduction in alveolar ventilation occurring during sleep. This is characterized by a rise in arterial carbon dioxide. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Vertebral segmentation defect (HP:0003422): An abnormality related to a defect of vertebral separation during development. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Intestinal pseudo-obstruction (HP:0004389): A functional rather than mechanical obstruction of the intestines, associated with manifestations that resemble those caused by an intestinal obstruction, including distension, abdominal pain, nausea, vomiting, constipation or diarrhea, in an individual in whom a mechanical blockage has been excluded. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Sagittal craniosynostosis (HP:0004442): A kind of craniosynostosis affecting the sagittal suture. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Lambdoidal craniosynostosis (HP:0004443): A kind of craniosynostosis affecting the lambdoidal suture. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Preauricular pit (HP:0004467): Small indentation anterior to the insertion of the ear. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Aortic aneurysm (HP:0004942): Aortic dilatation refers to a dimension that is greater than the 95th percentile for the normal person age, sex and body size. In contrast, an aneurysm is defined as a localized dilation of the aorta that is more than 150 percent of predicted (ratio of observed to expected diameter 1.5 or more). Aneurysm should be distinguished from ectasia, which represents a diffuse dilation of the aorta less than 50 percent of normal aorta diameter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Prominent metopic ridge (HP:0005487): Vertical bony ridge positioned in the midline of the forehead. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Abnormal primary tooth morphology (HP:0006481): Any abnormality of the primary tooth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Impaired pain sensation (HP:0007328): Reduced ability to perceive painful stimuli. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Eversion of lateral third of lower eyelids (HP:0007655). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Branchial anomaly (HP:0009794): Congenital developmental defect arising from the primitive branchial apparatus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Tooth agenesis (HP:0009804): The absence of one or more teeth from the normal series by a failure to develop. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Bifid tongue (HP:0010297): Tongue with a median apical indentation or fork. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Open bite (HP:0010807): Visible space between the dental arches in occlusion. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Typical absence seizure (HP:0011147): A typical absence seizure is a type of generalized non-motor (absence) seizure characterized by its sudden onset, interruption of ongoing activities, a blank stare, possibly a brief upward deviation of the eyes. Usually the patient will be unresponsive when spoken to. Duration is a few seconds to half a minute with very rapid recovery. Although not always available, an EEG would usually show 3 Hz generalized epileptiform discharges during the event. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Metopic synostosis (HP:0011330): Premature fusion of the metopic suture. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Nasogastric tube feeding in infancy (HP:0011470): Feeding problem necessitating nasogastric tube feeding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Type 1 muscle fiber atrophy (HP:0011807): Atrophy (wasting) affecting primary type 1 muscle fibers. This feature in general can only be observed on muscle biopsy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- Postaxial polydactyly (HP:0100259): A form of polydactyly in which the extra digit or digits are localized on the side of the fifth finger or fifth toe. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:453504)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:453504)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:453504)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Vesicoureteral reflux (HP:0000076): Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Open mouth (HP:0000194): A facial appearance characterized by a permanently or nearly permanently opened mouth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Dental malocclusion (HP:0000689): Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Gray matter heterotopia (HP:0002282): Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Exaggerated median tongue furrow (HP:0002711): Increased depth of the median tongue furrow. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:453504)
- Bruxism (HP:0003763): Bruxism is characterized by the grinding of the teeth including the clenching of the jaw and typically occur during sleep. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:453504)
These phenotypes are associated with the disease Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to a point mutation (ORPHA:453504).