Phenotypes associated with the disease neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (OMIM:617527):
- 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: 6/6. (PMID:28007986)
- Tented upper lip vermilion (HP:0010804): Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. Evidence: IEA. (OMIM:617527)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 6/11. (PMID:28413018;PMID:28007986)
- 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: 3/7. (PMID:28007986)
- Small joint hypermobility (HP:0430046): The capability that a small joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Small joints include metacarpophalangeal joints, proximal interphalangeal joints, nsecond to fifth metatarsophalangeal joints, and wrists. Evidence: PCS. Frequency: 6/7. (PMID:28007986)
- Cessation of head growth (HP:0004485): Stagnation of head growth seen as flattening of the head circumference curve. Evidence: PCS. Frequency: 6/6. (PMID:28413018)
- Short nose (HP:0003196): Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip. Evidence: PCS. Frequency: 1/7. (PMID:28413018)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: IEA. (OMIM:617527)
- 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: 13/15. (PMID:28413018)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: PCS. Frequency: 7/7. (PMID:28413018)
- 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: 11/12. (PMID:28413018;PMID:28007986)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 4/9. (PMID:28413018)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 1/7. (PMID:28413018)
- Single transverse palmar crease (HP:0000954): The distal and proximal transverse palmar creases are merged into a single transverse palmar crease. Evidence: PCS. Frequency: 3/7. (PMID:28413018)
- Long fingers (HP:0100807): The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand. Evidence: IEA. (OMIM:617527)
- Abnormal cortical gyration (HP:0002536): An abnormality of the gyri (i.e., the ridges) of the cerebral cortex of the brain. Evidence: PCS. Frequency: 10/10. (PMID:28413018)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. Frequency: 2/7. (PMID:28413018)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 6/8. (PMID:28413018;PMID:28007986)
- Progressive microcephaly (HP:0000253): Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms. Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Periventricular cysts (HP:0007109). Evidence: PCS. Frequency: 1/1. (PMID:28413018)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 1/7. (PMID:28413018)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 6/6. (PMID:28413018)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 6/7. (PMID:28007986)
- 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:28007986)
- 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: 8/12. (PMID:28413018;PMID:28007986)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. (PMID:28413018)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: IEA. (OMIM:617527)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 3/7. (PMID:28413018)
- 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: 14/14. (PMID:28413018;PMID:28007986)
- Contractures of the large joints (HP:0005781). Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 6/6. (PMID:28413018)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Postaxial polydactyly (HP:0100259): A form of polydactyly in which the extra digit or digits are localized on the side of the fifth finger or fifth toe. Evidence: PCS. Frequency: 2/7. (PMID:28413018)
- Progressive leukoencephalopathy (HP:0006980): Leukoencephalopathy that gets more severe with time. Evidence: PCS. Frequency: 9/9. (PMID:28413018)
- 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:28007986)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 4/4. (PMID:28413018)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: PCS. Frequency: 7/7. (PMID:28413018)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 3/7. (PMID:28413018)
- Edema of the dorsum of hands (HP:0007514): An abnormal accumulation of fluid beneath the skin on the back of the hands. Evidence: PCS. Frequency: 2/7. (PMID:28413018)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. (PMID:28413018)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: PCS. Frequency: 2/7. (PMID:28413018)
- 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: 6/6. (PMID:28413018)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 17/17. (PMID:28413018;PMID:28007986)
- 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: 1/7. (PMID:28413018)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 14/17. (PMID:28413018;PMID:28007986)
- Bulbar signs (HP:0002483). Evidence: PCS. Frequency: 7/10. (PMID:28413018)
- Delayed fine motor development (HP:0010862): A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands. Evidence: PCS. Frequency: 6/6. (PMID:28413018)
- 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: 7/7. (PMID:28007986)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 8/8. (PMID:28413018)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Edema of the dorsum of feet (HP:0012098): An abnormal accumulation of fluid beneath the skin on the back of the feet. Evidence: PCS. Frequency: 4/7. (PMID:28413018)
- Hypomimic face (HP:0000338): A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation. Evidence: IEA. (OMIM:617527)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 5/9. (PMID:28413018;PMID:28007986)
- 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: 2/7. (PMID:28413018)
- Congenital hypothyroidism (HP:0000851): A type of hypothyroidism with congenital onset. Evidence: PCS. Frequency: 1/7. (PMID:28413018)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/1. (PMID:28413018)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: IEA. (OMIM:617527)
- 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: 7/7. (PMID:28007986)
- Bulbar palsy (HP:0001283): Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia. Evidence: PCS. Frequency: 4/4. (PMID:28413018)
- Wide cavum septum pellucidum (HP:0034964): Width of the cavum septum pellucidum above the upper limit of normal, which is defined as a separation of greater than one cm of the leaves of the cavum septum pellucidum. Evidence: PCS. Frequency: 3/3. (PMID:28413018)
- Respiratory insufficiency (HP:0002093). Evidence: IEA. (OMIM:617527)
- Rocker bottom foot (HP:0001838): The presence of both a prominent heel and a convex contour of the sole. Evidence: PCS. Frequency: 2/7. (PMID:28007986)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Palmoplantar hyperhidrosis (HP:0007410): An abnormally increased perspiration on palms and soles. Evidence: PCS. Frequency: 6/7. (PMID:28413018)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: PCS. Frequency: 7/7. (PMID:28007986)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/7. (PMID:28413018)