- Aplasia/Hypoplasia of the optic nerve (HP:0008058). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Profound global developmental delay (HP:0012736): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Slow pupillary light response (HP:0030211): Reduced velocity and acceleration in the pupillary light response. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- 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. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- 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. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- Central sleep apnea (HP:0010536): Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- 5-minute APGAR score of 1 (HP:0030921). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- 1-minute APGAR score of 0 (HP:0030927). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:423479)
- Profound intellectual disability (HP:0002187): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:423479)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- 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: Frequent (HP:0040282). (ORPHA:423479)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Retinal dystrophy (HP:0000556): Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Diabetes insipidus (HP:0000873): A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Macular pseudocoloboma (HP:0001116): A so-called macular coloboma is characterized by a sharply defined, usually excavated, area without neuroretina and RPE tissues in the central area of the fundus. This lesion is not related to classical colobomas associated with optic fissure closure defects. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Severe failure to thrive (HP:0001525). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Limb hypertonia (HP:0002509). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- 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: Frequent (HP:0040282). (ORPHA:423479)
- Elevated amniotic fluid alpha-fetoprotein concentration (HP:0004639): An elevation of alpha-feto protein measured in the amniotic fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Hyperactive deep tendon reflexes (HP:0006801). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
- Undetectable visual evoked potentials (HP:0007965). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:423479)
These phenotypes are associated with the disease X-linked intellectual disability-limb spasticity-retinal dystrophy-arginine vasopressin deficiency (ORPHA:423479).
The following phenotypes are NOT associated with this disease:
- HbH hemoglobin (HP:0011903): Hemoglobin H (HbH) contains four beta-globin chains. It is normally not present at all in blood, but may make up about 1-40 percent of all hemoglobin in HbH disease, a subform of alpha thalassemia. Evidence: TAS. (ORPHA:423479)