Phenotypes associated with the disease neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities (OMIM:620732):
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/4. (PMID:35880319;PMID:30564627)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Hypoplasia of the brainstem (HP:0002365): Underdevelopment of the brainstem. Evidence: PCS. Frequency: 3/3. (PMID:35880319;PMID:30564627)
- Heat intolerance (HP:0002046): The inability to maintain a comfortable body temperature in warm or hot weather. Evidence: PCS. Frequency: 2/2. (PMID:30564627)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Myoclonic seizure (HP:0032794): A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 1/4. (PMID:35880319;PMID:30564627)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- 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: 3/3. (PMID:35880319;PMID:30564627)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: PCS. Frequency: 3/3. (PMID:35880319;PMID:30564627)
- Akathisia (HP:0031943): A state of motor restlessness, usually in the lower extremities, that is often but not always accompanied by a subjective sense of inner restlessness, an urge to move, and anxiety or dysphoria. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Hypoplasia of the pons (HP:0012110): Underdevelopment of the pons. Evidence: PCS. Frequency: 3/3. (PMID:35880319;PMID:30564627)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 1/4. (PMID:35880319;PMID:30564627)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/3. (PMID:35880319;PMID:30564627)
- Protruding ear (HP:0000411): Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective). Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- Hypoplastic anterior commissure (HP:0030303): Underdevelopment of the anterior commissure. Evidence: PCS. Frequency: 1/3. (PMID:35880319;PMID:30564627)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 0/4. (PMID:35880319;PMID:30564627)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 3/3. (PMID:35880319;PMID:30564627)
- Orofacial dyskinesia (HP:0002310). Evidence: PCS. Frequency: 4/4. (PMID:35880319;PMID:30564627)
- 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: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- 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: 3/4. (PMID:35880319;PMID:30564627)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 2/2. (PMID:30564627)
- 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: 4/4. (PMID:35880319;PMID:30564627)
- Sleep onset insomnia (HP:0031354): Difficulty initiating sleep, that is, increased sleep onset latency, refers to the condition where it takes 30 minutes or more to fall asleep. Evidence: PCS. Frequency: 2/2. (PMID:30564627)
- 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: PCS. Frequency: 1/4. (PMID:35880319;PMID:30564627)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 2/3. (PMID:35880319;PMID:30564627)
- Tonic seizure (HP:0032792): A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening. Evidence: PCS. Frequency: 1/4. (PMID:35880319;PMID:30564627)
- Limb hypertonia (HP:0002509). Evidence: PCS. Frequency: 2/2. (PMID:30564627)
- Hypotelorism (HP:0000601): Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes). Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- 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:30564627)
- Sensory neuropathy (HP:0000763): Peripheral neuropathy affecting the sensory nerves. Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- 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:35880319)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 2/4. (PMID:35880319;PMID:30564627)