Phenotypes associated with the disease neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (OMIM:619026):
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- 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: PCS. Frequency: 11/12. (PMID:32707086)
- Decreased motor nerve conduction velocity (HP:0003431): A type of decreased nerve conduction velocity that affects the motor neuron. Evidence: PCS. Frequency: 1/8. (PMID:32707086)
- Failure to thrive in infancy (HP:0001531). Evidence: PCS. Frequency: 3/12. (PMID:32707086)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- 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: 5/12. (PMID:32707086)
- 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: 9/12. (PMID:32707086)
- Elevated brain lactate level by MRS (HP:0012707): An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 3/4. (PMID:32707086)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 8/12. (PMID:32707086)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 12/12. (PMID:32707086)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- 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: 1/12. (PMID:32707086)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Decreased sensory nerve conduction velocity (HP:0003448): Reduced speed of conduction of the action potential along a sensory nerve. Evidence: PCS. Frequency: 3/8. (PMID:32707086)
- Exodeviation (HP:0020049): A manifest or latent ocular deviation in which one or both eyes tends to deviate temporally. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 12/12. (PMID:32707086)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 9/12. (PMID:32707086)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 6/12. (PMID:32707086)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 7/11. (PMID:32707086)
- Axial dystonia (HP:0002530): A type of dystonia that affects the midline muscles, i.e., the chest, abdominal, and back muscles. Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: PCS. Frequency: 6/12. (PMID:32707086)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 7/12. (PMID:32707086)
- 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:32707086)
- Long eyelashes (HP:0000527): Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective). Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 8/12. (PMID:32707086)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 2/12. (PMID:32707086)
- Spastic paraplegia (HP:0001258): Complete loss of the ability to move the lower limbs accompanied by spasticity of the lower limbs. Evidence: PCS. Frequency: 12/12. (PMID:32707086)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 4/12. (PMID:32707086)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: PCS. Frequency: 12/12. (PMID:32707086)
- External ophthalmoplegia (HP:0000544): Paralysis of the external ocular muscles. Evidence: PCS. Frequency: 1/12. (PMID:32707086)
- Respiratory failure requiring assisted ventilation (HP:0004887): A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation. Evidence: PCS. Frequency: 5/12. (PMID:32707086)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. Frequency: 3/5. (PMID:32707086)