Table 2.

Disorders to Consider in the Differential Diagnosis of SYNE1 Deficiency

MOIDisorderGene 1Clinical Features of Differential Diagnosis Disorder
Overlapping w/SYNE1 DeficiencyDistinguishing from SYNE1 Deficiency
ARSCA-AR, 10 (SCAR10; ARCA3)
(See Hereditary Ataxia Overview.)		 ANO10
  • Very similar clinically
  • Pure cerebellar ataxia w/occasional UMN signs
  • Cognitive impairment
  • Absence of polyneuropathy
  • Marked cerebellar atrophy
Seen mainly in Europe (whereas SYNE1 deficiency is seen worldwide)
Primary coenzyme Q10 deficiency
(SCAR9; ARCA2)		 COQ8A Often a pure cerebellar ataxia phenotype w/cognitive impairment & cerebellar atrophy
  • Exercise intolerance
  • Epilepsy
  • Myoclonus
  • Occasional stroke-like cerebral lesions
  • Absence of UMN &/or LMN signs
Friedreich ataxia FXN
  • Cerebellar ataxia
  • Positive Babinski signs
  • Sensory involvement w/spinal cord atrophy
  • Abolished reflexes
  • Square-wave jerks
  • Hypertrophic cardiomyopathy
  • Childhood to teenage onset
  • Absence of cerebellar atrophy
Boucher-Neuhäuser syndrome & PNPLA6-related Gordon Holmes syndrome
(See PNPLA6-Related Disorders.)		 PNPLA6
  • Cerebellar ataxia
  • Spasticity
  • Hyperreflexia
  • Hypogonadotropic hypogonadism
  • Chorioretinal dystrophy
  • Childhood onset
  • Pontine atrophy
ARSACS
(AR spastic ataxia of Charlevoix-Saguenay)		 SACS
  • Ataxia
  • Dysarthria
  • Eye movement abnormalities
  • UMN signs
  • Seen worldwide but high prevalence in French Canadians
  • Infantile or childhood onset
  • Sensorimotor neuropathy
  • Retinal striation
  • Frequent mitral valve prolapse
Spastic paraplegia 7 SPG7
  • Pyramidal signs w/spasticity
  • Cerebellar ataxia w/cerebellar atrophy
  • Spastic paraparesis more predominant
  • Optic neuropathy
  • Ptosis
AD SCA3 ATXN3
  • Cerebellar ataxia
  • UMN signs w/occasional amyotrophy & fasciculations
  • Cognitive impairment
  • Extrapyramidal features w/dystonia, rigidity, parkinsonism
  • Progressive external ophthalmoparesis
SCA6 CACNA1A
  • Cerebellar ataxia w/adult onset & slow progression
  • Occasional UMN signs
Extrapyramidal features w/dystonia & blepharospasm
XLFragile X-associated tremor/ataxia syndrome (FXTAS) (See FMR1-Related Disorders.) FMR1
  • Cerebellar ataxia of adult onset
  • Cognitive impairment
  • Predominant tremor
  • Parkinsonism
  • MRI: White matter lesions in cerebellar peduncles & brain stem

AD = autosomal dominant; AR = autosomal recessive; LMN = lower motor neuron; MOI = mode of inheritance; SCA = spinocerebellar ataxia; UMN = upper motor neuron; XL = X-linked

1.

Within a MOI, genes are in alphabetic order.

From: SYNE1 Deficiency

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