- 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: 1/1. (PMID:24044690)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- 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: 7/12. (PMID:28100473)
- Trigonocephaly (HP:0000243): Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput. Evidence: PCS. Frequency: 2/7. (PMID:26647312;PMID:24044690;PMID:23383720)
- 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: 4/15. (PMID:26647312;PMID:28100473)
- 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: 14/15. (PMID:26647312;PMID:28100473)
- 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: 4/7. (PMID:26647312;PMID:23383720)
- 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: 2/4. (PMID:23383720)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 9/12. Onset: Congenital onset (HP:0003577). (PMID:28100473)
- Thin eyebrow (HP:0045074): Decreased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Deep palmar crease (HP:0006191): Excessively deep creases of the palm. Evidence: PCS. Frequency: 3/4. (PMID:23383720)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 4/19. (PMID:26647312;PMID:28100473;PMID:23383720)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- 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: 4/17. (PMID:24044690;PMID:28100473;PMID:23383720)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Dental crowding (HP:0000678): Changes in alignment of teeth in the dental arch. Evidence: PCS. Frequency: 2/12. (PMID:28100473)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- 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: 1/12. (PMID:28100473)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 2/16. (PMID:28100473;PMID:23383720)
- 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: 16/16. (PMID:26647312;PMID:28100473;PMID:23383720)
- Laryngomalacia (HP:0001601): Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- 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: 4/20. (PMID:26647312;PMID:24044690;PMID:28100473;PMID:23383720)
- Hand clenching (HP:0001188): An abnormal hand posture in which the hands are clenched to fists. All digits held completely flexed at the metacarpophalangeal and interphalangeal joints. In prenatal sonography of the fetal clenched hand, the index finger overlaps a clenched fist formed by the other digits. The proximal interphalangeal articulation of the index finger is flexed and ulnarly deviated, and the thumb is adducted. Evidence: PCS. Frequency: 2/4. (PMID:23383720)
- 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: 5/7. (PMID:26647312;PMID:23383720)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 8/15. (PMID:26647312;PMID:28100473)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/8. (PMID:26647312;PMID:24044690;PMID:23383720)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 5/8. (PMID:26647312;PMID:24044690;PMID:23383720)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Choanal stenosis (HP:0000452): Abnormal narrowing of the choana (the posterior nasal aperture). Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/3. (PMID:26647312)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 2/3. (PMID:26647312)
- 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: 12/15. (PMID:26647312;PMID:28100473)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- 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: 4/4. (PMID:26647312;PMID:24044690)
- Tube feeding (HP:0033454): Feeding problem necessitating food and nutrient delivery via a tube. Evidence: PCS. Frequency: 3/4. Onset: Infantile onset (HP:0003593). (PMID:23383720)
- Recurrent hand flapping (HP:0100023): A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically. Evidence: PCS. Frequency: 3/12. (PMID:28100473)
- 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: 10/13. (PMID:24044690;PMID:28100473)
- Metopic synostosis (HP:0011330): Premature fusion of the metopic suture. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- 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: 0/3. (PMID:26647312)
- 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:23383720)
- 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: 4/7. (PMID:26647312;PMID:23383720)
- 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: 1/4. (PMID:23383720)
- Scaphocephaly (HP:0030799): Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Sloping forehead (HP:0000340): Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- 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: 1/1. (PMID:24044690)
- 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: 5/8. (PMID:26647312;PMID:24044690;PMID:23383720)
- 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: 2/7. (PMID:26647312;PMID:23383720)
- Short columella (HP:0002000): Reduced distance from the anterior border of the naris to the subnasale. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/4. (PMID:26647312;PMID:24044690)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 1/3. (PMID:26647312)
- Ulnar deviation of the hand (HP:0009487): Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger). Evidence: PCS. Frequency: 3/7. (PMID:26647312;PMID:23383720)
- Inferior cerebellar vermis hypoplasia (HP:0007068): Underdevelopment of the inferior portion of the vermis of cerebellum. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- 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: 1/1. (PMID:24044690)
- 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: 1/12. (PMID:28100473)
- 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: 11/16. (PMID:28100473;PMID:23383720)
- Broad nasal tip (HP:0000455): Increase in width of the nasal tip. Evidence: PCS. (PMID:28100473)
- Gingival overgrowth (HP:0000212): Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Supernumerary nipple (HP:0002558): Presence of more than two nipples. Evidence: PCS. Frequency: 1/4. (PMID:23383720)
- Breech presentation (HP:0001623): A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- 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. (PMID:28100473)
- Arachnodactyly (HP:0001166): Abnormally long and slender fingers (spider fingers). Evidence: PCS. Frequency: 2/12. (PMID:28100473)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/12. Onset: Fetal onset (HP:0011461). (PMID:28100473)
- 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: 12/12. (PMID:28100473)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/3. (PMID:26647312)
- 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. (PMID:28100473)
- Everted lower lip vermilion (HP:0000232): An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view. Evidence: PCS. (PMID:28100473)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 2/5. (PMID:24044690;PMID:23383720)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 4/4. (PMID:23383720)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Contracture of the proximal interphalangeal joint of the 4th finger (HP:0009276): Chronic loss of joint motion of the proximal interphalangeal joint of the 4th finger due to structural changes in non-bony tissue. That is, the PIP joint of a fourth finger is bent (flexed) and cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement. Evidence: PCS. Frequency: 1/12. (PMID:28100473)
- Disproportionate tall stature (HP:0001519): A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim. Evidence: PCS. Frequency: 3/12. (PMID:28100473)
- Precocious puberty (HP:0000826): The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys. Evidence: PCS. Frequency: 1/2. (PMID:26647312)
- Nasogastric tube feeding (HP:0040288): The condition of inability to eat normally treated by placement of a thin tube through the nose into the stomach that is then used to carry food. Evidence: PCS. Frequency: 3/3. (PMID:26647312)
- Periorbital fullness (HP:0000629): Increase in periorbital soft tissue. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 3/12. (PMID:28100473)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: PCS. Frequency: 1/1. (PMID:24044690)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/3. Onset: Fetal onset (HP:0011461). (PMID:26647312)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: PCS. Frequency: 2/12. (PMID:28100473)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. (PMID:28100473)
- 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: 1/4. (PMID:23383720)
- 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: 1/12. (PMID:28100473)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 2/12. (PMID:28100473)
These phenotypes are associated with the disease severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (OMIM:615485).