- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: TAS. (OMIM:300523)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: TAS. (OMIM:300523)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: TAS. (OMIM:300523)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: TAS. (OMIM:300523)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: IEA. (OMIM:300523)
- 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: IEA. (OMIM:300523)
- 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. (OMIM:300523)
- 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. (OMIM:300523)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: IEA. (OMIM:300523)
- Hallux valgus (HP:0001822): Lateral deviation of the great toe (i.e., in the direction of the little toe). Evidence: IEA. (OMIM:300523)
- 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. (OMIM:300523)
- 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. (OMIM:300523)
- Leukodystrophy (HP:0002415): Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies. Evidence: IEA. (OMIM:300523)
- 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:300523)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: IEA. (OMIM:300523)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: IEA. (OMIM:300523)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. (OMIM:300523)
- Prominent antihelix (HP:0000395): The presence of an abnormally prominent antihelix. Evidence: TAS. (OMIM:300523)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: TAS. (OMIM:300523)
- Rotary nystagmus (HP:0001583): A form of nystagmus in which the eyeball makes rotary motions around the axis. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:300523)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. (OMIM:300523)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: TAS. (OMIM:300523)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: TAS. (OMIM:300523)
- 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: TAS. (OMIM:300523)
- Stahl ear (HP:0100015): The presence of a supernumerary, i.e. third, crus of the helix in the helix, arising at or above the normal bifurcation of the antihelix. Evidence: IEA. (OMIM:300523)
- Underfolded superior helices (HP:0008583): A condition in which the superior portion of the helix is folded over to a lesser degree than normal. Evidence: PCS. (PMID:15488219)
- X-linked recessive inheritance (HP:0001419): A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. Evidence: PCS. (PMID:15980113)
- 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: PCS. (PMID:15488219)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: IEA. (OMIM:300523)
- Elevated circulating thyroid-stimulating hormone concentration (HP:0002925): Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation. Evidence: TAS. (OMIM:300523)
- Abnormal conjugate eye movement (HP:0000549): Any deviation from the normal motor coordination of the eyes that allows for bilateral fixation on a single object. Evidence: IEA. (OMIM:300523)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: TAS. (OMIM:300523)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: TAS. (OMIM:300523)
- 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: IEA. (OMIM:300523)
- Spastic paraplegia (HP:0001258): Complete loss of the ability to move the lower limbs accompanied by spasticity of the lower limbs. Evidence: TAS. (OMIM:300523)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: PCS. (PMID:15488219)
These phenotypes are associated with the disease Allan-Herndon-Dudley syndrome (OMIM:300523).