- 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: Very frequent (HP:0040281). (ORPHA:163681)
- 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:163681)
- Abnormality of neuronal migration (HP:0002269): An abnormality resulting from an anomaly of neuronal migration, i.e., of the process by which neurons travel from their origin to their final position in the brain. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:163681)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:163681)
- Abnormal neuron morphology (HP:0012757): A structural anomaly of a neuron. Neurons are electrically excitable cells that transmit signals throughout the body. Neurons employ both electrical and chemical components in the transmission of information. Neurons are connected to other neurons at synapses and connected to effector organs or cells at neuroeffector junctions. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:163681)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:163681)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Progressive language deterioration (HP:0007064): Progressive loss of previously present language abilities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Bilateral tonic-clonic seizure with focal onset (HP:0007334): A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- EEG with generalized slow activity (HP:0010845): Diffuse slowing of cerebral electrical activity recorded along the scalp by electroencephalography (EEG). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Interictal epileptiform activity (HP:0011182): Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- EEG with generalized epileptiform discharges (HP:0011198): EEG discharges recorded on the entire scalp typically seen in persons with epilepsy. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- EEG with generalized polyspikes (HP:0012001): EEG with repetitive generalized sharp transient waves of a duration less than 80 msec. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:163681)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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:163681)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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: Occasional (HP:0040283). (ORPHA:163681)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Self-mutilation (HP:0000742): Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Low frustration tolerance (HP:0000744): The feeling of frustration can be defined as an emotional reaction that occurs when a desired goal is not achieved. Frustration intolerance is defined as an age-inappropriate response to frustration, characterized by crying or temper tantrums in children, or aggressive or other maladaptive behaviors. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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:163681)
- 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: Occasional (HP:0040283). (ORPHA:163681)
- 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:163681)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Obesity (HP:0001513): Accumulation of substantial excess body fat. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Intermittent hyperventilation (HP:0004879): Episodic hyperventilation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Cerebellar vermis atrophy (HP:0006855): Wasting (atrophy) of the vermis of cerebellum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Periventricular leukomalacia (HP:0006970): Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Receptive language delay (HP:0010863): A delay in the acquisition of the ability to understand the speech of others. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- EEG with focal spikes (HP:0011193): EEG with focal sharp transient waves of a duration less than 80 msec. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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: Occasional (HP:0040283). (ORPHA:163681)
- Skin-picking (HP:0012166): Repetitive and compulsive picking of skin which results in tissue damage. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- 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: Occasional (HP:0040283). (ORPHA:163681)
- Abnormal temper tantrums (HP:0025160): Temper tantrums are brief episodes of extreme, unpleasant, and sometimes aggressive behaviors in response to frustration or anger, which are a normal part of development in toddlers. Temper tantrums that occur more frequently in a given time and/or are more severe in symptomatology and/or longer in duration and/or inappropriate for the given age compared to a temper tantrum that naturally occurs as a part of the developmental process are classified as abnormal temper tantrums. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Cerebral palsy (HP:0100021): Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
- Preaxial polydactyly (HP:0100258): A form of polydactyly in which the extra digit or digits are localized on the side of the thumb or great toe. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:163681)
These phenotypes are associated with the disease CNTNAP2-related developmental and epileptic encephalopathy (ORPHA:163681).