Phenotypes associated with the disease PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (ORPHA:438213):
- 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:438213)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:438213)
- Broad-based gait (HP:0002136): An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:438213)
- Floppy infant (HP:0008947): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:438213)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:438213)
- Neurodevelopmental delay (HP:0012758): Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:438213)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Abnormality of vision (HP:0000504): Abnormality of eyesight (visual perception). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Soft skin (HP:0000977): Subjective impression of increased softness upon palpation of the skin. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- 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:438213)
- Excessive daytime somnolence (HP:0001262): A state of abnormally strong desire for sleep during the daytime. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Exaggerated startle response (HP:0002267): An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Hypoventilation (HP:0002791): A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Breathing dysregulation (HP:0005957). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- 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: Frequent (HP:0040282). (ORPHA:438213)
- Receptive language delay (HP:0010863): A delay in the acquisition of the ability to understand the speech of others. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Stereotypical hand wringing (HP:0012171): Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- 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:438213)
- Decreased circulating vitamin D concentration (HP:0100512): The concentration of vitamin D in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:438213)
- Abnormality of the genitourinary system (HP:0000119): The presence of any abnormality of the genitourinary system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- 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: Occasional (HP:0040283). (ORPHA:438213)
- Hypermetropia (HP:0000540): An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Abnormality of the endocrine system (HP:0000818): An abnormality of the endocrine system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Abnormality of the skeletal system (HP:0000924): An abnormality of the skeletal system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- 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:438213)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Deep philtrum (HP:0002002): Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Myopathic facies (HP:0002058): A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Involuntary movements (HP:0004305): Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- 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: Occasional (HP:0040283). (ORPHA:438213)
- Bilateral tonic-clonic seizure on awakening (HP:0007193): Bilateral tonic-clonic seizure of either generalized or focal onset occurring on or soon after wakening (typically within 90 minutes of waking, regardless of the time of day). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Eversion of lateral third of lower eyelids (HP:0007655). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Almond-shaped palpebral fissure (HP:0007874): A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- High anterior hairline (HP:0009890): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Generalized tonic seizure (HP:0010818): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Epileptic spasm (HP:0011097): A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur: Grimacing, head nodding, or subtle eye movements. Epileptic spasms frequently occur in clusters. Infantile spasms are the best known form, but spasms can occur at all ages. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Widened subarachnoid space (HP:0012704): An increase in size of the anatomic space between the arachnoid membrane and pia mater. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Exophoria (HP:0025313): A form of strabismus with one or both eyes deviated outward to a milder degree than with exotropia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Hyperintensity of cerebral white matter on MRI (HP:0030890): A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Brown anomaly (HP:0031622): An ocular motility defect where the affected eye(s) does not elevate in adduction but has full depression in adduction. It can be congenital or acquired from injury to or defect of the superior oblique tendon or trochlea and has a positive forced duction test result. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:438213)
- 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:438213)
- Vesicoureteral reflux (HP:0000076): Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Uterine prolapse (HP:0000139): The presence of prolapse of the uterus. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- 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: Very rare (HP:0040284). (ORPHA:438213)
- Kidney stone (HP:0000787): Kidney stones (calculi) are mineral concretions in the renal calyces and pelvis that are found free or attached to the renal papillae. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- 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: Very rare (HP:0040284). (ORPHA:438213)
- Increased circulating prolactin concentration (HP:0000870): The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- 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: Very rare (HP:0040284). (ORPHA:438213)
- Absent septum pellucidum (HP:0001331): Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- 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: Very rare (HP:0040284). (ORPHA:438213)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- 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:438213)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Bicuspid aortic valve (HP:0001647): The presence of an aortic valve with two instead of the normal three cusps (flaps). Bicuspid aortic valvue is a malformation of a commissure (small space between the attachment of each cusp to the aortic wall) and the adjacent parts of the two corresponding cusps forming a raphe (the fused area of the two underdeveloped cusps turning into a malformed commissure between both cusps; the raphe is a fibrous ridge that extends from the commissure to the free edge of the two underdeveloped, conjoint cusps). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Abnormality of the anterior pituitary (HP:0011747): An abnormality of the adenohypophysis, which is also known as the anterior lobe of the pituitary gland. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Anomalous origin of left subclavian artery (HP:0031253): Origin of the left subclavian artery from an anomalous anatomical location. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)
- Decreased circulating iron concentration (HP:0040303): The concentration of iron cation in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:438213)