- 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: 1/3. (PMID:32103185)
- 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: 1/3. (PMID:32103185)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/3. (PMID:32103185)
- 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: 3/3. Onset: Infantile onset (HP:0003593). (PMID:32103185)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: PCS. Frequency: 2/3. (PMID:32103185)
- 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: 1/3. (PMID:32103185)
- 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: 1/3. Onset: Infantile onset (HP:0003593). (PMID:32103185)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. (PMID:32103185)
- 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: 1/3. (PMID:32103185)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 2/3. (PMID:32103185)
- Round face (HP:0000311): The facial appearance is more circular than usual as viewed from the front. Evidence: PCS. Frequency: 2/3. (PMID:32103185)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 2/3. (PMID:32103185)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 3/3. (PMID:32103185)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/3. (PMID:32103185)
- Craniosynostosis (HP:0001363): Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth. Evidence: PCS. Frequency: 1/3. (PMID:32103185)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 3/3. (PMID:32103185)
- 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: 1/3. Onset: Infantile onset (HP:0003593). (PMID:32103185)
- 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: 3/3. (PMID:32103185)
- Death in adolescence (HP:0011421): Death during adolescence, the period between childhood and adulthood (roughly between the ages of 10 and 16 years). Evidence: PCS. Frequency: 1/3. (PMID:32103185)
- Choroid plexus cyst (HP:0002190): A cyst occurring within the choroid plexus within a cerebral ventricle. Evidence: PCS. Frequency: 1/3. Onset: Infantile onset (HP:0003593). (PMID:32103185)
- 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: 1/3. (PMID:32103185)
- 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:32103185)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 2/3. (PMID:32103185)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 1/3. (PMID:32103185)
- 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: 3/3. (PMID:32103185)
These phenotypes are associated with the disease neurodevelopmental disorder with microcephaly, seizures, and brain atrophy (OMIM:619076).