- 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: 1/2. (PMID:24784135)
- Abnormality of the dentition (HP:0000164): Any abnormality of the teeth. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- 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: PCS. Frequency: 1/2. (PMID:26050939)
- 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: 0/1. (PMID:25804403)
- 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: 2/3. (PMID:25823418;PMID:26050939)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/2. (PMID:24482476)
- Delayed ability to crawl (HP:0033128): A failure to achieve the ability to crawl at an appropriate developmental stage. Normal infant motor development is marked by a series of postural milestones including learning to crawl on hands and knees between the ages of 6 and 10 months. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/2. (PMID:24482476)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: PCS. Frequency: 2/2. (PMID:24784135)
- 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: PCS. Frequency: 1/2. (PMID:26050939)
- 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: 1/2. (PMID:24482476)
- 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: PCS. Frequency: 2/2. (PMID:26050939)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 1/2. (PMID:24482476)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/4. (PMID:24784135;PMID:26050939)
- Congenital nystagmus (HP:0006934): Nystagmus dating from or present at birth. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/2. (PMID:24784135)
- 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: PCS. Frequency: 2/2. (PMID:24482476)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- 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:25823418;PMID:24784135;PMID:26050939;PMID:24482476;PMID:25804403)
- 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: 1/2. (PMID:26050939)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Autosomal recessive inheritance (HP:0000007): 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:24482476)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: PCS. Frequency: 3/3. (PMID:24784135;PMID:25804403)
- 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: PCS. Frequency: 2/2. (PMID:24482476)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- 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: 1/1. (PMID:25804403)
- 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: 1/2. (PMID:24784135)
- 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: PCS. Frequency: 1/2. (PMID:24482476)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 3/3. (PMID:25823418;PMID:24784135)
- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: PCS. Frequency: 2/2. (PMID:24784135)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- 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: PCS. Frequency: 2/2. (PMID:25823418;PMID:25804403)
- Enamel hypoplasia (HP:0006297): Developmental hypoplasia of the dental enamel. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- Motor stereotypy (HP:0000733): Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose. Evidence: PCS. Frequency: 2/2. (PMID:24784135)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 2/2. (PMID:24482476)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/2. (PMID:24482476)
- 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: 1/1. (PMID:25823418)
- Delayed ability to roll over (HP:0032989): Delayed achievement of the ability to roll front to back and back to front. Evidence: PCS. Frequency: 2/2. (PMID:26050939)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:24784135)
- Prominent antihelix (HP:0000395): The presence of an abnormally prominent antihelix. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- 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: 1/1. (PMID:25823418)
- 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: 5/5. (PMID:24784135;PMID:24482476;PMID:25804403)
- Secundum atrial septal defect (HP:0001684): A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 2/2. (PMID:24784135)
- Enlarged sylvian cistern (HP:0100952): An increase in size of the subarachnoid space associated with the lateral cerebral sulcus (Sylvian fissure). Evidence: PCS. Frequency: 2/3. (PMID:25823418;PMID:24482476)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: PCS. Frequency: 1/1. (PMID:25823418)
- Inappropriate laughter (HP:0000748): Laughing that may be excessive and/or inappropriate in context (e.g., laughing at a funeral while others are crying). Evidence: PCS. Frequency: 1/2. (PMID:26050939)
- Divergence nystagmus (HP:0030691): A condition in which both eyes beat outward simultaneously. Evidence: PCS. Frequency: 1/1. (PMID:25804403)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: PCS. Frequency: 2/2. (PMID:24784135)
These phenotypes are associated with the disease intellectual disability, autosomal recessive 42 (OMIM:615802).