Table 1.
Clinical features and genetic diagnosis of patients with movement disorders
| Patient | Sex | Ethnicity | Movement disorders | Location | Clinical course | Onset | Dysmorphic features | Congenital anomalies | Other clinical features | Brain MRI features | aCGH findings | Variants found | Inherit- ance |
ACMG classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases with pathogenic or likely pathogenic variants found | ||||||||||||||
| 12 | M | Chinese | Dystonia | Generalized |
Non- progressive |
Infancy | + | – | Mild ID, blue sclera, easy fracture | Normal | Not done | Heterozygous CTNNB1: c.367C > T, p.(Q123*); Heterozygous COL1A1: c.343G > T, p.(G115*) (incidental finding) | De novo | Pathogenic |
| 14 | M | Chinese | Spastic paraplegia with both upper limbs involvement | Generalized | Progressive | Infancy | – | – | – | Periventricular white matter change | Not done | Heterozygous SPAST: c.1253_1255delAAG, p.(Glu418del) | De novo | Pathogenic |
| 17 | M | Chinese | Dystonia, Choreoathetosis with status dystonicus | Generalized | Progressive | Infancy | – | – | Mild to moderate ID, Rhabdomyolysis | Normal | Not done | Heterozygous GNAO1: c.625C > T, p.(Arg209Cys) | Parents’ DNA not available | Likely pathogenic |
| 19 | M | Chinese | Spastic paraplegia | Lower limbs | Progressive | Early child- hood | – | – | Attention deficit hyperactivity disorder | Periventricular white matter changes with corpus callosum thinning | Not done | Compound heterozygous SPG11: c.4462_4463del, p.(V1488fs) & c.1569G > A, p.(W523*) | Paternal & Maternal | Likely pathogenic |
| 20 | M | Chinese | Rigidity with parkinsonism features, Spasticity, Paroxysmal worsening of parkinsonism | Generalized |
Non- progressive |
Birth | – | Pulmonary stenosis | Obstructive Sleep Apnoea Syndrome, Severe ID, laryngomalacia | Progressive cerebellar atrophy | Not done | Heterozygous ATP1A3: c.954C > G, p.(Ile318Met) | De novo | Pathogenic |
| 23 | M | Chinese | Dystonia | Generalized |
Non- progressive |
Infancy | + | – | Severe ID, Epilepsy | Normal | Normal | Heterozygous PURA: c.783C > G, p.(Tyr261*) | De novo | Pathogenic |
| 27 | M | Chinese | Cerebellar ataxia, spasticity | Generalized |
Non- progressive |
Infancy | – | – | Reactive hypoglycaemia, Mild ID | Normal | Not done | Heterozygous SLC2A1: c.388G > C, p.(Gly130Arg) # | De novo | Pathogenic |
| 29 | M | Chinese | Dystonia, Spasticity | Generalized | Progressive | 6y | – | Left atrophic kidney | Fatty liver, Recurrent patellar dislocation, prominent capillaries | Normal | Not done | Heterozygous KMT2B: c.2425C > T, p.(Gln809*) | De novo | Pathogenic |
| 30 | F | Pakistani | Cerebellar ataxia, spasticity, rigidity | Generalized | Progressive | 13y | – | – | Neuromuscular weakness | Periventricular white matter changes with corpus callosum thinning | Not done | Homozygous SPG11: c.5399_5402delinsTGGAGGAG:p.(Gln1800fs) | Paternal & Maternal | Likely pathogenic |
| 31 | M | Chinese | Dystonia, spasticity | Generalized | Progressive | Infancy | – | – | Bilateral hearing impairment, autism spectrum disorder, learning problem (formal IQ not available) | Normal | Not done |
Heterozygous ACTB: c.547C > T:p.(Arg183Trp) |
De novo | Pathogenic |
| Cases with variants of unknown significance (VUS) found | ||||||||||||||
| 1 | M | Chinese | Cerebellar ataxia | Generalized | Non-progressive | 6y | – | – | Limited intelligence with dementia, bipolar affective disorder | Stable cerebellar atrophy | Not done | Heterozygous KCND3: c.1917C > A, p.(Asn639Lys) | Maternal | VUS |
| 6 | M | Chinese | Dystonia, Spasticity | Generalized | Non-progressive | Birth | + | – | Mild ID, severe intrauterine growth retardation, autism spectrum disorder | Right parietal lobe developmental venous anomaly | Normal | Compound heterozygous VPS13D: c.5300C > T, p.(Thr1767Ile) & c.8213A > C, p.(Gln2738Pro) | Paternal & Maternal | VUS |
| 7 | F | Chinese | Dystonia, Spasticity | Generalized | Non-progressive | Birth | + | – | Mild ID to limited intelligence, intrauterine growth retardation | Dysgenesis of corpus callosum | Not done | Compound heterozygous VPS13D: c.5300C > T, p.(Thr1767Ile) & c.8213A > C, p.(Gln2738Pro) | Paternal & Maternal | VUS |
| 8 | F | Chinese | Cerebellar ataxia, Spasticity | Generalized | Non-progressive | Infancy | – | – | Mild ID with dementia, Ichthyosis | Progressive cerebellar atrophy | Not done | Heterozygous KCNC3: c.2105G > T, p.(Ser702Ile) | Paternal | VUS |
MRI Magnetic resonance imaging; ACMG American College of Medical Genetics, VUS variant of unknown significance, y years, ID intellectual disability; IQ intelligence quotient
#The family declined lumbar puncture