Phenotypes associated with the disease congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (OMIM:615574):
- Exaggerated startle response (HP:0002267): An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face. Evidence: PCS. Frequency: 14/21. (OMIM:615574;PMID:27469131;PMID:24139043)
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: TAS. (OMIM:615574)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: TAS. (OMIM:615574)
- Large hands (HP:0001176). Evidence: TAS. (OMIM:615574)
- 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: 1/1. (PMID:29375865)
- Caudate atrophy (HP:0002340). Evidence: PCS. Frequency: 1/2. (PMID:27469131)
- Moderate to late preterm birth (HP:0025664): Birth at 32 to 36 completed weeks of gestation. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- 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: 1/2. (PMID:27469131)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/6. (PMID:24139043)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- 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: 2/3. (PMID:27469131;PMID:29375865)
- Hypoplasia of the pons (HP:0012110): Underdevelopment of the pons. Evidence: PCS. Frequency: 8/12. (PMID:27469131;PMID:28776279;PMID:24139043)
- Dilated third ventricle (HP:0007082): An increase in size of the third ventricle. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- 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: PCS. Frequency: 1/2. (PMID:27469131)
- Cortical dysplasia (HP:0002539): The presence of developmental dysplasia of the cerebral cortex. Evidence: TAS. (OMIM:615574)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Simple ear (HP:0020206): The pinna has fewer folds and grooves than usual. Evidence: PCS. Frequency: 1/2. (PMID:27469131)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 4/6. (PMID:24139043)
- Progressive microcephaly (HP:0000253): Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms. Evidence: TAS. (OMIM:615574)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 8/8. (PMID:24139043)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/2. (PMID:27469131)
- 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: 2/2. (PMID:27469131)
- Dilated fourth ventricle (HP:0002198): An abnormal dilatation of the fourth cerebral ventricle. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- 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: 1/1. (PMID:29375865)
- Profound global developmental delay (HP:0012736): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: TAS. (OMIM:615574)
- Optic nerve hypoplasia (HP:0000609): Underdevelopment of the optic nerve. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Third trimester onset (HP:0034197): This term refers to a phenotypic feature that was first observed prior to birth during the third trimester, which is defined as 28 weeks and zero days (28+0) of gestation and beyond. Evidence: PCS. Frequency: 3/3. (PMID:28776279)
- Primary microcephaly (HP:0011451): Head circumference below 2 standard deviations below the mean for age and gender at birth. Evidence: PCS. Frequency: 3/3. (PMID:27469131;PMID:29375865)
- Limb hypertonia (HP:0002509). Evidence: PCS. Frequency: 9/9. (PMID:24139043)
- 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:24139043)
- 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: TAS. (OMIM:615574)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- Hypoasparaginemia (HP:0500157): A decreased amount of asparagine in the blood. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- 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: 3/3. (PMID:27469131;PMID:29375865)
- Sloping forehead (HP:0000340): Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view. Evidence: PCS. Frequency: 2/3. (PMID:27469131;PMID:29375865)
- 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: 3/8. (PMID:24139043)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- 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: 1/2. (PMID:27469131)
- Hypoplasia of the brainstem (HP:0002365): Underdevelopment of the brainstem. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Prominent nasal tip (HP:0005274). Evidence: PCS. Frequency: 2/2. (PMID:27469131)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:615574)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- 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: 1/1. (PMID:28776279)
- 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: 1/1. (PMID:28776279)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- Clonic seizure (HP:0020221): A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/2. (PMID:27469131)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 11/12. (PMID:27469131;PMID:28776279;PMID:24139043)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/1. (PMID:28776279)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 6/11. (PMID:27469131;PMID:24139043)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- EEG with burst suppression (HP:0010851): The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes. Evidence: PCS. Frequency: 2/8. (PMID:24139043)
- 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: 9/9. (PMID:24139043)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. (OMIM:615574)
- Sleep apnea (HP:0010535): An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- Reduced cerebral white matter volume (HP:0034295): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 1/1. (PMID:29375865)
- Diaphragmatic eventration (HP:0009110): A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development. Evidence: PCS. Frequency: 2/2. (PMID:27469131)
- Long foot (HP:0001833): Increased back to front length of the foot. Evidence: TAS. (OMIM:615574)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 2/3. (PMID:27469131;PMID:28776279)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/2. (PMID:27469131)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. (OMIM:615574)
- Simplified gyral pattern (HP:0009879): An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly. Evidence: PCS. Frequency: 9/12. (PMID:27469131;PMID:24139043;PMID:29375865)