mds-pas school for young neurologists video dinner february 21, 2015 maria eliza t. freitas, md...
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MDS-PAS School for
Young NeurologistsVideo Dinner
February 21, 2015
Maria Eliza T. Freitas, MDClinical Fellow In Movement Disorder
University of TorontoToronto Western Hospital
History• 40 year-old male, right-handed
• Age of onset: 35 years
• Tremor and lack of dexterity in both hands
• Worse in the left side
• Slow and unsteady gait (2 falls)
• He denied:
- Symptoms of dysautonomia,
- Cognitive/ behavior impairment
- Dysarthria, dysphagia
• Past medical history: hypertension, dyslipidemia and gout
• Current medications: Crestor, Atenolol, Allopurinol
Video
Physical Exam
• No cognitive impairment or apraxia.
• Cranial nerves: Eye movements were full. There were slow saccades and
normal pursuit/VOR.
• No nystagmus.
• Motor exam showed normal muscle bulk and strength throughout. Reflexes were normal.
• Moderate rigidity in the upper limbs (worse in the left side).
• Mild rigidity in the lower limbs.
• No sensory abnormalities.
Differential Diagnosis
• Brain MRI: Normal
• Normal copper studies
Investigation
• Early onset Parkinsonism:
• Parkin (PARK2)
• PINK1 (PARK6)
• DJ-1-associated parkinsonism (PARK7)
• Neurodegeneration with brain iron accumulation (NBIA)
• Spinocerebellar atrophy (SCA) types 2 and 3
• X-linked dystonia-parkinsonism/Lubag (DYT3)
• Wilson’s disease
• Dopa-responsive dystonia (DYT5)
Summary• Early onset Parkinsonism (35yo)
• Asymmetric rest, postural and kinetic tremor (atypical tremor - dystonic)
• Postural instability
• Levodopa reduced hand tremor (no benefit for others symptoms)
• Not aware of on-off motor fluctuations
• Diphasic dyskinesia
• Mode of inheritance: Sex-linked recessive disorder
• History of ancestral roots from Panay Islands (Philippines)
Final Diagnosis
Target mutation analysis found the disease-specific
single-nucleotide change 3 (DSC3) in the TAF1/DYT3 gene:
X-linked recessive Dystonia-Parkinsonism: DYT3 or Lubag Disease
Phenomenology of the Tremor
Marsden’s Book of Movement Disorders, 2011
DYT3 - Lubag • Lee et al (2011): reviewed 505 cases
• Age of onset is 39-40 years
• Mean duration of illness is 16 years and mean age at death is 55.6 years.
• Onset with dystonia: 94.3% (focal)
• Onset with parkinsonism: 5.7%
• Focal dystonia spreads in 97% of the time and generalizes within 5 years in 84%
• Dyskinesia are unusual: levodopa-induced x clinical feature of Lubag
• Women: milder course and different phenotype
• Diagnosis: DSC3 mutation on Xq13
• Treatment: oral medications, Botulinum toxin, DBS
Dystonic phase Combined dystonia- Parkinsonian phase
parkinsonian phase
Pasco et al, 2011 Lee et al, 2011
Taking Home Messages
• DYT3 is a sex-linked recessive dystonia-parkinsonism
• This case has shown mainly parkinsonian symptoms with atypical features: dystonic tremor but no clear focal dystonia and also unusual dyskinesia (levodopa-induced or Lubag's dyskinesia?)
• DYT3 should be considered in men with progressive dystonia/parkinsonism, positive family history and ancestral roots from Philippine.
• Parkinsonism may be the only early feature in male patients with XDP preceding the onset of dystonia.
• Symptomatic carriers (women) have a milder phenotype, older age of onset, and mild parkinsonism with or without dystonia.
Evidente et al., 2004