- 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:90322)
- 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:90322)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:90322)
- Patchy demyelination of subcortical white matter (HP:0002545): Patchy loss of myelin from nerve fibers in the central nervous system. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:90322)
- Subcortical white matter calcifications (HP:0007346). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:90322)
- 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: Very frequent (HP:0040281). (ORPHA:90322)
- 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:90322)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
- Postural instability (HP:0002172): A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
- Progeroid facial appearance (HP:0005328): A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- 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:90322)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Conjunctivitis (HP:0000509): Inflammation of the conjunctiva. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Developmental cataract (HP:0000519): A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Anophthalmia (HP:0000528): Absence of the globe or eyeball. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Uveitis (HP:0000554): Inflammation of one or all portions of the uveal tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- 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:90322)
- 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:90322)
- Anodontia (HP:0000674): The absence of all teeth from the normal series by a failure to develop. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Delayed eruption of primary teeth (HP:0000680): Delayed tooth eruption affecting the primary dentition. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Hypermelanotic macule (HP:0001034): A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that 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 of joints. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Limb hypertonia (HP:0002509). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Enamel hypoplasia (HP:0006297): Developmental hypoplasia of the dental enamel. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Widely spaced primary teeth (HP:0006313): Increased space between the primary teeth. Note this phenotype should be distinguished from increased space due purely to microdontia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Microdontia of primary teeth (HP:0006347): Decreased size of the primary teeth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- 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:90322)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Scarring (HP:0100699): A scar refers to a lesion in which wound, burn, or sore has not healed completely and fibrous connective tissue has developed. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:90322)
- Male hypogonadism (HP:0000026): Decreased functionality of the male gonad, i.e., of the testis, with reduced spermatogenesis or testosterone synthesis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:90322)
- 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: Very rare (HP:0040284). (ORPHA:90322)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:90322)
These phenotypes are associated with the disease Cockayne syndrome type 2 (ORPHA:90322).