Phenotypes associated with the disease Alexander disease (ORPHA:58):
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- 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:58)
- 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: Very frequent (HP:0040281). (ORPHA:58)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Megalencephaly (HP:0001355): Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Nausea and vomiting (HP:0002017): Nausea is a commonly encountered symptom that has been defined as an unpleasant painless subjective feeling that one will imminently vomit. Vomiting has been defined as the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. While nausea and vomiting are often thought to exist on a temporal continuum, this is not always the case. There are situations when severe nausea may be present without emesis and less frequently, when emesis may be present without preceding nausea. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- 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: Very frequent (HP:0040281). (ORPHA:58)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Large face (HP:0100729). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:58)
- Abnormality of eye movement (HP:0000496): An abnormality in voluntary or involuntary eye movements or their control. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- 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:58)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Diplopia (HP:0000651): Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Emotional lability (HP:0000712): Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- 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:58)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:58)
- 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:58)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Aphasia (HP:0002381): An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Tetraplegia (HP:0002445): Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Hypotension (HP:0002615): Low Blood Pressure, vascular hypotension. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Sleep apnea (HP:0010535): An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Facial palsy (HP:0010628): Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- Recurrent singultus (HP:0100247): A contraction of the diaphragm that repeats several times per minute. In humans, the abrupt rush of air into the lungs causes the epiglottis to close, creating a hic sound. Also known as synchronous diaphragmatic flutter (SDF), or singultus, from the Latin singult, the act of catching one's breath while sobbing. The hiccup is an involuntary action involving a reflex arc. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:58)
- 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:58)
- 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:58)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Diabetes mellitus (HP:0000819): A group of abnormalities characterized by hyperglycemia and glucose intolerance. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Precocious puberty (HP:0000826): The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- 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:58)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Sudden cardiac death (HP:0001645): The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Chorea (HP:0002072): Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Infectious encephalitis (HP:0002383): A disorder of the brain caused by an infectious agent that presents with fever, headache, and an altered level of consciousness. There may also be focal or multifocal neurologic deficits, and focal or generalized seizure activity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Aqueductal stenosis (HP:0002410): Stenosis of the cerebral aqueduct (also known as the mesencephalic duct, aqueductus mesencephali, or aqueduct of Sylvius), which connects the third cerebral ventricle in the diencephalon to the fourth ventricle, which is between the pons and cerebellum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Bowel incontinence (HP:0002607): Involuntary fecal soiling in adults and children who have usually already been toilet trained. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Hyperlordosis (HP:0003307): Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Hyperpigmented nevi (HP:0007481). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Abnormal autonomic nervous system physiology (HP:0012332): A functional abnormality of the autonomic nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)
- Self-injurious behavior (HP:0100716): Self-aggression. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:58)