- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: PCS. Frequency: Occasional (HP:0040283). (PMID:24336167)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 12/12. (PMID:29721912)
- 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: PCS. Frequency: 1/13. (PMID:29721912)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: PCS. Frequency: 13/28. (PMID:29721912;PMID:24336167)
- 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: 5/14. (PMID:29721912;PMID:32395406)
- 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: 6/13. (PMID:29721912)
- Muscle spasm (HP:0003394): Sudden and involuntary contractions of one or more muscles. Evidence: PCS. Frequency: 4/13. (PMID:29721912)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Gowers sign (HP:0003391): A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs. Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- 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: 1/1. (PMID:32395406)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: PCS. Frequency: 15/15. (PMID:24336167)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: PCS. Frequency: 2/13. (PMID:29721912)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. Frequency: 15/15. (PMID:24336167)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 5/15. (PMID:24336167)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- Orofacial dyskinesia (HP:0002310). Evidence: PCS. Frequency: 10/15. (PMID:24336167)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- 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:29721912;PMID:32395406)
- Chorea (HP:0002072): Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. Evidence: PCS. Frequency: 10/15. (PMID:24336167)
- 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: 15/28. (PMID:29721912;PMID:24336167)
- Hypervalinemia (HP:0010910): The concentration of valine in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Cerebellar dysplasia (HP:0007033): Cerebellar dysplasia (abnormal growth or development) is defined by abnormal cerebellar foliation, white matter arborization, and gray-white matter junction. Cerebellar dysplasia is a neuroimaging finding that describes abnormalities of both the cerebellar cortex and white matter and is associated with variable neurodevelopmental outcome. Dysplasia may globally involve the cerebellum or affect only one cerebellar hemisphere. In addition, cerebellar dysplasia may be associated with cortical/subcortical cysts. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Amblyopia (HP:0000646): Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- 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:24336167)
- 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: 1/15. (PMID:24336167)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 10/15. (PMID:24336167)
- Increased total leukocyte count (HP:0001974): An abnormal increase in the number of leukocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- 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: 1/1. (PMID:32395406)
- 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: 1/1. (PMID:32395406)
- Extremely elevated creatine kinase (HP:0030235): An increased creatine kinase level more than 50X above the upper normal level. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 2/8. (PMID:29721912)
- Hyperlysinemia (HP:0002161): The concentration of lysine in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 13/13. (PMID:29721912)
- Perisylvian polymicrogyria (HP:0012650): Polymicrogyria (an excessive number of small gyri or convolutions) that is maximal in perisylvian regions (the regions that surround the Sylvian fissures), which may be symmetric or asymmetric and may extend beyond perisylvian regions. The Sylvian fissures often extend posteriorly and superiorly. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 2/13. (PMID:29721912)
- Encephalomalacia (HP:0040197): Encephalomalacia is the softening or loss of brain tissue after cerebral infarction, cerebral ischemia, infection, craniocerebral trauma, or other injury. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Difficulty running (HP:0009046): Reduced ability to run. Evidence: PCS. Frequency: 7/15. (PMID:24336167)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 2/8. (PMID:29721912)
- Soft, doughy skin (HP:0001027): A skin texture that is unusually soft (and may feel silky), and has a malleable consistency resembling that of dough. Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 12/12. (PMID:29721912)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/8. (PMID:29721912)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- 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: 11/11. (PMID:29721912;PMID:32395406)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 4/13. (PMID:29721912)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 1/13. (PMID:29721912)
- Hypoplastic anterior limbs of the internal capsule (HP:0034051): Underdevelopment of the frontal part (anterior crus or anterior limb) of the internal capsule. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Calf muscle hypertrophy (HP:0008981): Muscle hypertrophy affecting the calf muscles. Evidence: PCS. Frequency: 3/13. (PMID:29721912)
- 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: 2/15. (PMID:24336167)
- Increased CSF protein concentration (HP:0002922): Increased concentration of protein in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:32395406)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 4/10. (PMID:29721912)
These phenotypes are associated with the disease proximal myopathy with extrapyramidal signs (OMIM:615673).