- Severe short stature (HP:0003510): A severe degree of short stature, more than -4 SD from the mean corrected for age and sex. Evidence: IEA. (OMIM:133540)
- Opacification of the corneal stroma (HP:0007759): Reduced transparency of the stroma of cornea. Evidence: IEA. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- Limitation of joint mobility (HP:0001376): A reduction in the freedom of movement of one or more joints. Evidence: PCS. (OMIM:133540)
- Normal pressure hydrocephalus (HP:0002343): A form of hydrocephalus characterized by enlarged cerebral ventricles and normal cerebrospinal fluid (CSF) pressure upon lumbar puncture. Evidence: IEA. (OMIM:133540)
- Square pelvis bone (HP:0003278): An abnormally squared appearance of the bony pelvis, a normally rounded or basin-shaped structure. Evidence: TAS. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: IEA. (OMIM:133540)
- Delayed eruption of primary teeth (HP:0000680): Delayed tooth eruption affecting the primary dentition. Evidence: IEA. (OMIM:133540)
- Microcornea (HP:0000482): A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood. Evidence: IEA. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 5/15. (PMID:9443879)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: IEA. (OMIM:133540)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:133540)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 6/15. (PMID:9443879)
- 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: PCS. Frequency: 8/14. (PMID:9443879;PMID:18446857)
- Severe failure to thrive (HP:0001525). Evidence: IEA. (OMIM:133540)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: PCS. (OMIM:133540)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. (OMIM:133540)
- Decreased lacrimation (HP:0000633): Abnormally decreased lacrimation, that is, reduced tear production. Evidence: IEA. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- Peripheral dysmyelination (HP:0003469): Defective structure and function of myelin sheaths. Dysmyelination is distinguished from demyleination where there is destruction or damage of previously normal myelination. Evidence: PCS. (OMIM:133540)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: PCS. Frequency: 2/2. (PMID:18446857)
- Anhidrosis (HP:0000970): Inability to sweat. Evidence: IEA. (OMIM:133540)
- Dermal atrophy (HP:0004334): Partial or complete wasting (atrophy) of the skin. Evidence: IEA. (OMIM:133540)
- Hypoplastic pelvis (HP:0008839): Underdevelopment of the bony pelvis. Evidence: TAS. (OMIM:133540)
- Loss of facial adipose tissue (HP:0000292): Loss of normal subcutaneous fat tissue in the face. Evidence: IEA. (OMIM:133540)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Ivory epiphyses of the phalanges of the hand (HP:0010234): Sclerosis of the epiphyses of the phalanges of the fingers, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays. Evidence: IEA. (OMIM:133540)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: IEA. (OMIM:133540)
- Abnormality of visual evoked potentials (HP:0000649): An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex. Evidence: IEA. (OMIM:133540)
- 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: PCS. Frequency: 2/2. (PMID:18446857)
- Cerebellar calcifications (HP:0007352). Evidence: IEA. (OMIM:133540)
- Autosomal recessive inheritance (HP:0000007): 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:18446857)
- 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: IEA. (OMIM:133540)
- Microphthalmia (HP:0000568): A developmental anomaly characterized by abnormal smallness of one or both eyes. Evidence: IEA. (OMIM:133540)
- 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: IEA. (OMIM:133540)
- Reduced subcutaneous adipose tissue (HP:0003758): A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Hypoplasia of the iris (HP:0007676): Congenital underdevelopment of the iris. Evidence: IEA. (OMIM:133540)
- Decreased nerve conduction velocity (HP:0000762): A reduction in the speed at which electrical signals propagate along the axon of a neuron. Evidence: IEA. (OMIM:133540)
- Hypoplasia of teeth (HP:0000685): Developmental hypoplasia of teeth. Evidence: PCS. (OMIM:133540)
- Hypoplastic iliac wing (HP:0002866): Underdevelopment of the ilium ala. Evidence: IEA. (OMIM:133540)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: IEA. (OMIM:133540)
- 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: 3/3. (PMID:18446857)
- Patchy demyelination of subcortical white matter (HP:0002545): Patchy loss of myelin from nerve fibers in the central nervous system. Evidence: IEA. (OMIM:133540)
- Abnormal hair morphology (HP:0001595): An abnormality of the hair. Evidence: IEA. (OMIM:133540)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 7/18. (PMID:9443879;PMID:18446857)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: IEA. (OMIM:133540)
- Thickened calvaria (HP:0002684): The presence of an abnormally thick calvaria. Evidence: IEA. (OMIM:133540)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Abnormal peripheral myelination (HP:0003130): An abnormality of the myelination of motor and sensory peripheral nerves. These are axons for motor nerves and dendrites for sensory nerves in the strict anatomic sense. Evidence: IEA. (OMIM:133540)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:133540)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: IEA. Frequency: 11/14. (OMIM:133540)
- Arrhythmia (HP:0011675): Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both. Evidence: IEA. (OMIM:133540)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: TAS. (OMIM:133540)
- Dry hair (HP:0011359): Hair that lacks the luster (shine or gleam) of normal hair. Evidence: TAS. (OMIM:133540)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: IEA. (OMIM:133540)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Slender nose (HP:0000417). Evidence: IEA. (OMIM:133540)
- Subcortical white matter calcifications (HP:0007346). Evidence: IEA. (OMIM:133540)
- Abnormal pinna morphology (HP:0000377): An abnormality of the pinna, which is also referred to as the auricle or external ear. Evidence: IEA. (OMIM:133540)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:133540)
- Basal ganglia calcification (HP:0002135): The presence of calcium deposition affecting one or more structures of the basal ganglia. Evidence: IEA. (OMIM:133540)
- Increased cellular sensitivity to UV light (HP:0003224). Evidence: IEA. (OMIM:133540)
- Abnormal skin pigmentation (HP:0001000): An abnormality of the pigmentation of the skin. Evidence: IEA. (OMIM:133540)
- Carious teeth (HP:0000670): Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries. Evidence: PCS. Frequency: 7/12. (PMID:9443879;PMID:18446857)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:133540)
- Cutaneous photosensitivity (HP:0000992): An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin. Evidence: IEA. (OMIM:133540)
- Abnormal auditory evoked potentials (HP:0006958): An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex. Evidence: IEA. (OMIM:133540)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 2/3. (PMID:18446857)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: IEA. (OMIM:133540)
- Prematurely aged appearance (HP:0007495). Evidence: IEA. (OMIM:133540)
- Atypical scarring of skin (HP:0000987): Atypically scarred skin . Evidence: IEA. (OMIM:133540)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: IEA. (OMIM:133540)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 3/3. (PMID:18446857)
- 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: IEA. (OMIM:133540)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: IEA. (OMIM:133540)
These phenotypes are associated with the disease Cockayne syndrome type 2 (OMIM:133540).