Table 2.

Other Genes of Interest in the Differential Diagnosis of SGCE Myoclonus-Dystonia

Gene(s)DiffDx DisorderMOIKey Clinical Features of DiffDx Disorder
Overlapping w/SGCE-M-DDistinguishing from SGCE-M-D
ADCY5 ADCY5-related dyskinesia AD
  • Possible cause of isolated M-D 1
  • Often childhood onset 2
Typically assoc w/addl features (e.g., chorea, early motor delay, alternating hemiplegia of childhood)
ATM Variant ataxia-telangiectasia 3ARDystonia only or dystonia w/myoclonus may be present.
  • Observed in Mennonite families of Russian origin
  • High cancer frequency & adverse responses to chemotherapeutic agents assoc w/a common ATM haplotype & homozygosity for c.6200C>A
ATN1 DRPLA ADMyoclonus, epilepsyIn children:
  • Ataxia
  • Progressive intellectual deterioration
In adults:
  • Ataxia
  • Choreoathetosis
  • Dementia or character changes
ATP7B Wilson disease ARDystonia
  • Biochemical findings: ↓ serum copper & ceruloplasmin concentrations; ↑ urinary copper excretion
  • Kayser-Fleischer corneal ring
ATXN3 Spinocerebellar ataxia type 3 ADDystonia in 1 personCerebellar ataxia, pyramidal signs, pontocerebellar atrophy
CSTB Unverricht-Lundborg disease ARMyoclonus, seizures
  • Ataxia, incoordination, intentional tremor, & dysarthria
  • Emotional lability, depression, & mild ↓ in intellectual performance over time
EPM2A
NHLRC1 		Progressive myoclonus epilepsy, Lafora type ARMyoclonus, seizures
  • ↑ frequency & intractability of seizures
  • Cognitive decline apparent at or soon after onset of seizures
  • Dysarthria & ataxia appear early; spasticity appears late.
GCH1 GTP cyclohydrolase 1-deficient dopa-responsive dystonia ADM-D in 1 person 4
  • Dramatic & sustained response to levodopa
  • Typically presents w/gait disturbance, later development of parkinsonism, & diurnal fluctuation of symptoms
GNB1

GNB1 encephalopathy

ADM-D in 1 person w/comorbid OCD & mild DD, 5 neurodevelopmental delay, & other features incl dystonia in 46 others 61 person w/M-D:
  • Mild ID
  • Limited upgaze, hypotonia, & OCD
In others w/dystonia:
  • Notable DD & growth delay, seizures, hypotonia, abnormal MRI
  • Other symptoms may incl genitourinary & gastrointestinal abnormality, vision, hearing, cardiac, & hematologic abnormalities.
KCTD17 Myoclonic dystonia 26 (OMIM 616398)ADEarly-onset myoclonic jerks; development of dystonia later in life (in 4 persons)Early motor delay, severe lingual dystonia, & mild cognitive delay in 2 families w/splice variants 7
mtDNA

MERRF

MatMyoclonus; seizuresAtaxia & ragged red fibers on muscle biopsy
NKX2-1 8Benign hereditary chorea (OMIM 118700)ADMyoclonusDoes not demonstrate aggravation of jerks w/complex motor tasks (in contrast to action-induced myoclonus of M-D).
PRKCG Spinocerebellar ataxia type 14 ADM-D in 1 person 9Slowly progressive cerebellar ataxia, dysarthria, & nystagmus
RELN RELN myoclonus-dystonia 7AD
  • Seemingly typical adult-onset M-D reported in 3 families & 2 simplex cases
  • Alcohol responsiveness & psychiatric comorbidities (5 persons) 10
  • Mean onset: age 22 yrs
  • Latest onset: age 53 yrs
TOR1A DYT1 early-onset isolated dystonia ADUnusual presentation of alcohol-responsive M-D in 1 person 11Cervical dystonia is uncommon in DYT1 dystonia.
TTPA Ataxia with vitamin E deficiency ARDystonia
  • 1st symptoms incl progressive ataxia, clumsiness of hands, loss of proprioception, & areflexia.
  • Cerebellar atrophy
TUBB2B TUBB2B tubulinopathy (mild form) 12
(See Tubulinopathies Overview.)		ADM-D in 1 person
  • Mild cognitive impairment & skeletal anomalies
  • Asymmetric pachygyria & dysmorphic basal ganglia on neuroimaging 12

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; DiffDx = differential diagnoisis; ID = intellectual disability; Mat = maternal inheritance; M-D = myoclonus-dystonia; MOI = mode of inheritance; OCD = obsessive-compulsive disorder

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8.

Because of the association of hypothyroidism with pathogenic variants in NKX2-1, thyroid hormone screening should be considered in affected individuals. See OMIM 118700, 610978, 600635.

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11.

A male with alcohol-responsive M-D who had the typical three-base pair deletion in TOR1A and no pathogenic variant in SGCE was reported [Tezenas du Montcel et al 2006]. His mother was Ashkenazi Jewish and had only writer's cramp.

12.

From: SGCE Myoclonus-Dystonia

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