Phenotypes associated with the disease neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (OMIM:620224):
- 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: PCS. Frequency: 2/7. (PMID:31278393)
- 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: PCS. Frequency: 3/8. (PMID:31278393)
- 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: PCS. Frequency: 8/8. (PMID:31278393)
- 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: PCS. Frequency: 7/8. (PMID:31278393)
- Periventricular white matter hyperintensities (HP:0030891): Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Broad hallux (HP:0010055): Visible increase in width of the hallux without an increase in the dorso-ventral dimension. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- 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: PCS. Frequency: 1/8. (PMID:31278393)
- 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: PCS. Frequency: 7/7. (PMID:31278393)
- Facial capillary hemangioma (HP:0000996): Hemangioma, a benign tumor of the vascular endothelial cells with small endothelial spaces, occurring in the face. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 5/8. (PMID:31278393)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 3/7. (PMID:31278393)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 8/8. (PMID:31278393)
- Low anterior hairline (HP:0000294): 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 below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Autistic behavior (HP:0000729): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: PCS. Frequency: 4/6. (PMID:31278393)
- 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. Frequency: 1/7. (PMID:31278393)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Cervical spinal canal stenosis (HP:0008445): An abnormal narrowing of the cervical spinal canal. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Short thumb (HP:0009778): Hypoplasia (congenital reduction in size) of the thumb. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Short philtrum (HP:0000322): Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 3/7. (PMID:31278393)
- 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. Frequency: 1/8. (PMID:31278393)
- Autosomal dominant inheritance (HP:0000006): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:31278393)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Bilateral talipes equinovarus (HP:0001776): Bilateral clubfoot deformity. Evidence: PCS. Frequency: 2/8. (PMID:31278393)
- Preauricular pit (HP:0004467): Small indentation anterior to the insertion of the ear. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- 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: PCS. Frequency: 1/7. (PMID:31278393)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: PCS. Frequency: 4/7. (PMID:31278393)
- Turricephaly (HP:0000262): Tall head relative to width and length. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Continuous spike and waves during slow sleep (HP:0031491): Diffuse, bilateral and recently also unilateral or focal localization spike-wave occurring in slow sleep or non-rapid eye movement sleep. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Pain insensitivity (HP:0007021): Inability to perceive painful stimuli. Evidence: PCS. Frequency: 1/3. (PMID:31278393)
- 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: PCS. Frequency: 4/7. (PMID:31278393)
- Bulbous nose (HP:0000414): Increased volume and globular shape of the anteroinferior aspect of the nose. Evidence: PCS. Frequency: 2/7. (PMID:31278393)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- 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: PCS. Frequency: 1/7. (PMID:31278393)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 2/8. (PMID:31278393)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Torticollis (HP:0000473): Involuntary contractions of the neck musculature resulting in an abnormal posture of or abnormal movements of the head. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- 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: PCS. Frequency: 8/8. (PMID:31278393)
- Long nose (HP:0003189): Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 3/8. (PMID:31278393)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 8/8. (PMID:31278393)
- Inability to walk by childhood/adolescence (HP:0006915). Evidence: PCS. Frequency: 2/8. (PMID:31278393)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Broad thumb (HP:0011304): Increased thumb width without increased dorso-ventral dimension. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Telecanthus (HP:0000506): Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi. Evidence: PCS. Frequency: 1/7. (PMID:31278393)
- Chiari type I malformation (HP:0007099): Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line). Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- 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: PCS. Frequency: 2/7. (PMID:31278393)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 1/8. (PMID:31278393)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 4/7. (PMID:31278393)
- 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: PCS. Frequency: 1/8. (PMID:31278393)