Phenotypes associated with the disease TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome (ORPHA:488632):
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:488632)
- Progressive muscle weakness (HP:0003323). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:488632)
- EMG: chronic denervation signs (HP:0003444): Evidence of chronic denervation on electromyography. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:488632)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:488632)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- 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: Frequent (HP:0040282). (ORPHA:488632)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Abnormal periventricular white matter morphology (HP:0002518): A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Abnormal circulating lipid concentration (HP:0003119): Any deviation from the normal concentration of a lipid in the blood circulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Multifocal seizures (HP:0031165): Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:488632)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- 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: Occasional (HP:0040283). (ORPHA:488632)
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Sloping forehead (HP:0000340): Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Thick eyebrow (HP:0000574): Increased density/number and/or increased diameter of eyebrow hairs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Limb undergrowth (HP:0009826): Limb shortening because of underdevelopment of one or more bones of the extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- EEG with generalized epileptiform discharges (HP:0011198): EEG discharges recorded on the entire scalp typically seen in persons with epilepsy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- EMG: myokymic discharges (HP:0100288): The presence of spontaneous bursts of rapidly firing potentials that recur at regular intervals of 2-10 per second and are unaffected by voluntary effort. This is an electromyographic (EMG) finding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:488632)
- Neurogenic bladder (HP:0000011): A type of bladder dysfunction caused by neurologic damage. Neurogenic bladder can be flaccid or spastic. Common manifestatios of neurogenic bladder are overflow incontinence, frequency, urgency, urge incontinence, and retention. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- 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:488632)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- 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: Very rare (HP:0040284). (ORPHA:488632)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- 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: Very rare (HP:0040284). (ORPHA:488632)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Synophrys (HP:0000664): Meeting of the medial eyebrows in the midline. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Decreased response to growth hormone stimulation test (HP:0000824): Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Hyperthyroidism (HP:0000836): An abnormality of thyroid physiology characterized by excessive secretion of the thyroid hormones thyroxine (i.e., T4) and/or 3,3',5-triiodo-L-thyronine zwitterion (i.e., triiodothyronine or T3). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- 11 pairs of ribs (HP:0000878): Presence of only 11 pairs of ribs. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Eczematoid dermatitis (HP:0000964): Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Broad finger (HP:0001500): Increased width of a non-thumb digit of the hand. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Diastasis recti (HP:0001540): A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Oligohydramnios (HP:0001562): Diminished amniotic fluid volume in pregnancy. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Pulmonic stenosis (HP:0001642): A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Broad toe (HP:0001837): Visible increase in width of the non-hallux digit without an increase in the dorso-ventral dimension. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Asthma (HP:0002099): Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- 2-3 toe syndactyly (HP:0004691): Syndactyly with fusion of toes two and three. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Prominent metopic ridge (HP:0005487): Vertical bony ridge positioned in the midline of the forehead. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Bipolar affective disorder (HP:0007302): Bipolar disorder is an illness of mood characterized by alternating episodes of elevated and depressed moods, which are interspersed with euthymic periods. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Corneal opacity (HP:0007957): A reduction of corneal clarity. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Central adrenal insufficiency (HP:0011734): A form of adrenal insufficiency related to a lack of ACTH, which leads to a decrease in the production of cortisol by the adrenal glands. Aldosterone production is not usually affected. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Abnormal involuntary eye movements (HP:0012547): Anomalous movements of the eyes that occur without the subject wanting them to happen. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:488632)