- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Wide anterior fontanel (HP:0000260): Enlargement of the anterior fontanelle with respect to age-dependent norms. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Delayed cranial suture closure (HP:0000270): Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Low anterior hairline (HP:0000294): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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: Frequent (HP:0040282). (ORPHA:235)
- 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: Frequent (HP:0040282). (ORPHA:235)
- Blepharophimosis (HP:0000581): A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Eczematoid dermatitis (HP:0000964): Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Hoarse voice (HP:0001609): Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Abnormally high-pitched voice (HP:0001620): A persistent (minutes to hours) abnormal increase in the pitch (frequency) of the voice for the context or social situation or significantly different from baseline of the individual. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Short foot (HP:0001773): A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Sandal gap (HP:0001852): A widely spaced gap between the first toe (the great toe) and the second toe. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Sparse scalp hair (HP:0002209): Decreased number of hairs per unit area of skin of the scalp. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Fine hair (HP:0002213): Hair that is fine or thin to the touch. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Sparse lateral eyebrow (HP:0005338): Decreased density/number and/or decreased diameter of lateral eyebrow hairs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Abnormal antihelix morphology (HP:0009738): An abnormality of the antihelix. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Neurodevelopmental delay (HP:0012758): Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Small hand (HP:0200055): Disproportionately small hand. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Abnormality of the dentition (HP:0000164): Any abnormality of the teeth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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:235)
- Photophobia (HP:0000613): Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Dental crowding (HP:0000678): Changes in alignment of teeth in the dental arch. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Delayed eruption of teeth (HP:0000684): Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Hypoparathyroidism (HP:0000829): A condition caused by a deficiency of parathyroid hormone characterized by hypocalcemia and hyperphosphatemia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Sacral dimple (HP:0000960): A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Abnormal skin pigmentation (HP:0001000): An abnormality of the pigmentation of the skin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Abnormal fingernail morphology (HP:0001231): An abnormality of the fingernails. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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:235)
- 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: Occasional (HP:0040283). (ORPHA:235)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: Occasional (HP:0040283). (ORPHA:235)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Toe syndactyly (HP:0001770): Webbing or fusion of the 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 toes in a proximo-distal axis are referred to as "Symphalangism". Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Hypoplastic toenails (HP:0001800): Underdevelopment of the toenail. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Metatarsus adductus (HP:0001840): The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Abnormality of neutrophils (HP:0001874): A neutrophil abnormality. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Malabsorption (HP:0002024): Impaired ability to absorb one or more nutrients from the intestine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Anal stenosis (HP:0002025): Abnormal narrowing of the anal opening. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Rectal prolapse (HP:0002035): Protrusion of the rectal mucous membrane through the anus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Asthma (HP:0002099): Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Spina bifida occulta (HP:0003298): The closed form of spina bifida with incomplete closure of a vertebral body with intact overlying skin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Aplasia/Hypoplasia of the corpus callosum (HP:0007370): Absence or underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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:235)
- Abnormal cardiovascular system morphology (HP:0030680): Any structural anomaly of the heart and blood vessels. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- Auditory hypersensitivity (HP:5200060): Hyperresponsive to sound that is abnormal in intensity and/or frequency. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:235)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Megalocornea (HP:0000485): An enlargement of the cornea with normal clarity and function. Megalocornea is diagnosed with a horizontal corneal diameter of 12 mm or more at birth or 13 mm or more after two years of age. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Microphthalmia (HP:0000568): A developmental anomaly characterized by abnormal smallness of one or both eyes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Iris coloboma (HP:0000612): A coloboma of the iris. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Decreased response to growth hormone stimulation test (HP:0000824): Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Neoplasm (HP:0002664): An organ or organ-system abnormality that consists of uncontrolled autonomous cell-proliferation which can occur in any part of the body as a benign or malignant neoplasm (tumor). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Lymphoma (HP:0002665): A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Acute lymphoblastic leukemia (HP:0006721): A form of acute leukemia characterized by excess lympoblasts. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:235)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- 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. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- Aplasia/Hypoplasia of the thumb (HP:0009601): Hypoplastic/small or absent thumb. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- Abnormality of thumb phalanx (HP:0009602): A structural anomaly of one or more phalanges of the thumb. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- Underdeveloped supraorbital ridges (HP:0009891): Flatness of the supraorbital portion of the frontal bones. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- Broad thumb (HP:0011304): Increased thumb width without increased dorso-ventral dimension. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:235)
- 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:235)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- Abnormal female external genitalia morphology (HP:0000055): Any structural abnormality of the female external genitalia. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:235)
- 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:235)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:235)
These phenotypes are associated with the disease Dubowitz syndrome (ORPHA:235).