Phenotypes associated with the disease neurodevelopmental disorder with seizures, hypotonia, and variable spasticity (OMIM:621482):
- 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: 1/1. (PMID:41533792)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/1. (PMID:41533792)
- 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: 5/9. (PMID:41533792)
- 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: PCS. Frequency: 7/10. (PMID:41533792)
- 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: PCS. Frequency: 2/9. (PMID:41533792)
- 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: 2/2. (PMID:41533792)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 4/7. (PMID:41533792)
- 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: PCS. Frequency: 7/10. (PMID:41533792)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 10/10. (PMID:41533792)
- 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: PCS. Frequency: 5/5. (PMID:41533792)
- Arm dystonia (HP:0031960): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the arms. Evidence: PCS. Frequency: 1/1. (PMID:41533792)
- Caesarean section (HP:0011410): Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy). Evidence: PCS. Frequency: 1/10. (PMID:41533792)
- Appendicular hypotonia (HP:0012389): Muscular hypotonia of one or more limbs. Evidence: PCS. Frequency: 2/10. (PMID:41533792)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 6/7. (PMID:41533792)
- 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: 10/10. (PMID:41533792)
- Downturned corners of mouth (HP:0002714): A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure. Evidence: PCS. Frequency: 6/9. (PMID:41533792)
- Fetal distress (HP:0025116): An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile. Evidence: PCS. Frequency: 1/10. (PMID:41533792)
- Large earlobe (HP:0009748): Increased volume of the earlobe, that is, abnormally prominent ear lobules. Evidence: PCS. Frequency: 8/10. (PMID:41533792)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 7/9. (PMID:41533792)
- Torticollis (HP:0000473): Involuntary contractions of the neck musculature resulting in an abnormal posture of or abnormal movements of the head. Evidence: PCS. Frequency: 1/1. (PMID:41533792)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/9. (PMID:41533792)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 9/9. (PMID:41533792)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/9. (PMID:41533792)
- 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: 5/5. (PMID:41533792)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 6/10. (PMID:41533792)
- 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: 5/7. (PMID:41533792)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 3/10. (PMID:41533792)
- Febrile seizure (within the age range of 3 months to 6 years) (HP:0002373): A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years. Evidence: PCS. Frequency: 3/3. (PMID:41533792)
- Bilateral tonic-clonic seizure with generalized onset (HP:0025190): A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure. Evidence: PCS. Frequency: 5/5. (PMID:41533792)
- 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: PCS. Frequency: 10/10. (PMID:41533792)
- Joint contracture (HP:0034392): A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part. Evidence: PCS. Frequency: 2/6. (PMID:41533792)
- Appendicular spasticity (HP:0034353): A type of spasticity that affects one or more limbs (arms or legs). Evidence: PCS. Frequency: 1/5. (PMID:41533792)
- 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: 6/9. (PMID:41533792)
- 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: 5/8. (PMID:41533792)
- Limb hypertonia (HP:0002509). Evidence: PCS. Frequency: 8/10. (PMID:41533792)
- 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:41533792)
- 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: PCS. Frequency: 1/1. (PMID:41533792)
- Upper limb spasticity (HP:0006986). Evidence: PCS. Frequency: 1/1. (PMID:41533792)