PARKINSONISM
CORTICAL/ SUBCORTICAL
HUNTINGTON DISEASE (HTT 4p16.3)
CHOREA (90%)
PSYCHIATRIC MANIFESTATIONS
PARKINSONISM/ DYSTONIA
ATAXIA/TICS
NO FAMILY HISTORY IN 8%
HDL1 (PRPN)
EARLY TO MID ADULTHOOD
FAMILIAL PRION DISEASE
PHENOTYPES:
GENETIC CREUTZFELDT JACKOB DISEASE
FAMILIAL FATAL INSOMNIA
GERSTMANN STRAUSSLER DISEASE (PRPN MUTATION)
PSYCHIATRIC MANIFESTATIONS
CHOREA/ PARKINSONISM
ATAXIA/ MYOCLONUS
HDL2 (CAG REPEAT >40 JPH3)
EARLY TO MID-ADULTHOOD
CLINICALLY SIMILAR TO HUNTINGTON'S DISEASE
PSYCHIATRIC MANIFESTATIONS
DEMENTIA/ ATAXIA
CHOREA/ PARKINSONISM
CREUTZFELDT JACOB DISEASE
AKINETIC MUTISM
PARKINSONISM
SPASTICITY/ MYOCLONUS
C9ORF72 (ALS-FTD)
AGE OF ONSET 8-80YRS
PARKINSONISM/ CHOREA
DYSTONIA/ ATAXIA (RARE)
30% PRESENT WITH MOVEMENT DISORDER
PHENOTYPES:
HD/FTD
PSP/ CBS/ MSA
MND/ PLS
NIID (NOTCH2NLC GGC REPEAT)
ACTION/ POSTURAL TREMOR
DEMENTIA (ALZEIMER'S TYPE)
PARKINSONISM/ DYSTONIA/ CHOREA
ATAXIA(50%)
PERIPHERAL NEUROPATHY/ LIMB WEAKNESS
PERIPHERAL DENERVATION
AUTONOMIC DYSFUNCTION: MIOSIS
DRY COUGH
PHENOTYPE:
FXTAS PHENOTYPE
MSA/ PD PHENOTYPE
MRI: CORTICOMEDULLARY JUNCTION
DWI RIBBON-LIKE HYPER-INTENSITIES
LEUKODYSTROPHY
BASAL GANGLIA
PARKINSONISM (PRIMARY)
FBX07
PYRAMIDAL/ PSYCHIATRY
CHOREA/ VSGP
MINERAL DEPOSIT DISORDERS
PKAN (PANK2)
TYPICAL PKAN:
AGE OF ONSET <12YRS
DYSARTHRIA/ DYSTONIA/ OPISTHOTONUS
PRAYING MANTIS SIGN/ CHOREA
PARKINSONISM/ SPASTICITY/ OPTIC ATROPHY
RETINITIS PIGMENTOSA (25%)
ACANTHOCYTES (8%)
ATYPICAL PKAN:
EARLY CHILDHOOD TO LATE ADULTHOOD
SLOWER PROGRESSION
NEUROPSYCHIATRIC MANIFESTATIONS
OCD/ IMPULSIVITY/ DEPRESSION
PALILALIA/ TICS
CAN MIMIC JUVENILE PARKINSONISM
CAN MIMIC TOURETTE SYNDROME
RX: DEFERIPRONE 30MG/KG/DAY
MAY BE USEFUL (MIXED RESULTS)
DBS MAY BE USEFUL
PLAN (PLA2G6)
DYSTONIA/ PARKINSONISM
ATAXIA/ SPASTICITY
LEVODOPA-INDUCED EARLY DYSKINESIA
INVOLVING LOWER FACE
TRUNCAL DYSTONIA
PHENOTYPES:
DYSTONIA PARKINSONISM
SPASTIC PARAPARESIS
CEREBELLAR ATAXIA
SENDA (BPAN) (WDR45)
BIPHASIC CLINICAL PROFILE
CHILDHOOD-ONSET:
COGNITIVE DECLINE/RETT-LIKE PHENOTYPE
AUTISM/ STEREOTYPE/ SEIZURES
ADOLESCENCE OR ADULTHOOD ONSET:
SPASTICITY/ PARKINSONISM/ DYSTONIA
RARELY CHOREA
OTHER FEATURES:
SEIZURES/ LENNOX GESTAUT SYNDROME
BILATERAL OPTIC ATROPHY
RX: LEVODOPA PARTIALLY RESPONSIVE
VAC14
AGE OF ONSET 6-15YRS
COGNITION
FOCAL DYSTONIA/ PARKINSONISM
ATAXIA/ SPASTICITY
RETINITIS PIGMENTOSA
NEUROFERRITINOPATHY
ORO-MANDIBULAR DYSKINESIA (85%)
JAW DYSTONIA/ BLEPHAROSPASM
FOCAL LOWER LIMB CHOREA /DYSTONIA
ACUTE BALLISMUS
LESS COMMON: ATAXIA/ PARKINSONISM/ TICS/TREMOR
LIP-SMACKING/ WRITER'S CRAMP
FRONTAL SUBCORTICAL COGNITIVE DYSFUNCTION
ACERULOPLASMINEMIA
AGE OF ONSET 30-70YRS
OROFACIAL DYSTONIA/ CERVICAL DYSTONIA
COGNITIVE DECLINE/ ATAXIA/ TREMOR/ CHOREA
PARKINSONISM (20%)
DIABETES MELLITUS/ LIVER DYSFUNCTION
RETINAL DEGENERATION
LAB: ABSENT CERULOPLASMIN
HETEROZYGOUS: MODERATELY REDUCED LEVEL
INCREASED FERRITIN
RX: DEFERIPRONE STARTING DOSE 15MG/KG/DAY
TWO DIVIDED DOSES
CAN TITRATE TO MAX 50MG/KG/DAY
PHLEBOTOMY 300ML EVERY 15 DAYS
WOODHOUSE SAKATI SYNDROME (DCAF17)
SPECTRUM: RAPIDLY DISABLING TO MILD SYMPTOMS
COGNITIVE DECLINE
DEAFNESS/ DYSTONIA/ CHOREA
PARKINSONISM/ ATAXIA
ALOPECIA./ DIABETES/ HYPOGONADISM
TRIANGULAR FACE/ HYPERTELORISM
KUFOR RAKEB SYNDROME (ATP13A2)
PARK9/ SPG78
COGNITION/ PARKINSONISM/ VSGP
VISUAL HALLUCINATION
OCULOGYRIC CRISIS
SPG78: LATE SPASTICITY WITHOUT PARKINSONISM
FACIAL-FAUCIAL-FINGER-MYOCLONUS
WILSON DISEASE
LIVER/ NEUROLOGICAL/ PSYCHIATRY
DYSTONIA/ CHOREA/ PARKINSONISM
DEPRESSION/ OCD/ PHOBIAS
PROTEINURIA/ ARTHRITIS/SUNFLOWER CATARACT
CARDIOMYOPATHY/ ARRHYTHMIA
FAHR SYNDROME
NEUROPSYCHIATRIC/ SEIZURES/ HEADACHE
PARKINSONISM/ DYSTONIA/ CHOREA
ATAXIA/ TREMOR
SLC20A2
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM
PDGFB
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM/ ATAXIA/ CHOREA
PDGFRB
COGNITION/ HEADACHE/ SEIZURES
PARKINSONISM
XPR1
COGNITION/ HEADACHE
PARKINSONISM/ ATAXIA
MYORG
COGNITION/ PARKINSONISM/ ATAXIA
JAM2
COGNITION/ PARKINSONISM/ ATAXIA/ DYSTONIA
MRI: CALCIFICATION
BG/ THALAMUS/ CEREBELLUM/ WM
MYORG: CENTRAL PONS CALCIFICATION
LYSOSOMAL (BG)
NIEMANN PICK C DISEASE
VSGP/ GELASTIC CATAPLEXY
ATAXIA/ DYSTONIA/ CHOREA
HEPATOSPLENOMEGALY
THROMBOCYTOPENIA
NEUROACANTHOCYTOSIS
CHOREA-ACANTHOCYTOSIS (VPS13A)
AGE OF ONSET 20-60YRS
ACTION TONGUE DYSTONIA
FEEDING DYSTONIA/ TICS
RUBBER-MAN GAIT/DROP ATTACK
NEUROPATHY/ MYOPATHY
PSYCHIATRIC MANIFESTATIONS/ SEIZURE
HEPATO-SPLENOMEGALY
LAB: CPK/ LFT ELEVATED
ACANTHOCYTES ARE TO BE SEEN IN 1:1 DILUTION IN NORMAL SALINE WITH A PHASE CONTRAST MICROSCOPE
ACANTHOCYTE CAN BE ABSENT
MCLEOD (XK)
COGNITION/ CHOREA
PSYCHIATRIC SYMPTOMS/ SEIZURES
NEUROPATHY/ MYOPATHY
CHF/ ATRIAL FIBRILLATION
HAEMOLYSIS
MRI: CAUDATE/ PUTAMEN ATROPHY
WHM
SPORADIC
POLYCYTHEMIA VERA
INCREASED HEMOGLOBIN LEVEL
THROMBOSIS
NEUROPATHY
CORTEX/ SUBCORTICAL
NIID (NOTCH2NLC GGC REPEAT)
ACTION/ POSTURAL TREMOR
DEMENTIA (ALZEIMER'S TYPE)
PARKINSONISM/ DYSTONIA
ATAXIA(50%)
PERIPHERAL NEUROPATHY
PERIPHERAL DENERVATION
AUTONOMIC DYSFUNCTION: MIOSIS
PHENOTYPE:
FXTAS PHENOTYPE
MSA/ PD PHENOTYPE
MRI: CORTICOMEDULLARY JUNCTION
DWI RIBBON-LIKE HYPER-INTENSITIES
LEUKODYSTROPHY
BASAL GANGLIA
NEUROACANTHOCYTOSIS
CHOREA-ACANTHOCYTOSIS (VPS13A)
AGE OF ONSET 20-60YRS
ACTION TONGUE DYSTONIA
FEEDING DYSTONIA/ TICS
PARKINSONISM (MAY BE PRESENTING SIGN)
RUBBER-MAN GAIT (KNEE AND HIP BUCKING)
DROP ATTACK
NEUROPATHY/ MYOPATHY
PSYCHIATRIC MANIFESTATIONS/ SEIZURE
HEPATO-SPLENOMEGALY
LAB: CPK/ LFT ELEVATED
ACANTHOCYTES ARE TO BE SEEN IN 1:1 DILUTION IN NORMAL SALINE WITH A PHASE CONTRAST MICROSCOPE
ACANTHOCYTE CAN BE ABSENT
CEREBELLUM/ TRACTS
AOA PHENOTYPE
ATAXIA TELANGIECTASIA
TELANGIECTASIA OVER
EYES/ SUN EXPOSED AREAS
OCULOMOTOR APRAXIA
DYSTONIA/ CHOREA/ MYOCLONUS
PARKINSONISM/ ATAXIA
TREMOR/ NEUROPATHY
LYMPHOMA/ LEUKEMIA (EARLY)
SOLID TUMOUR (LATE)
LAB: LOW IGA/ IGG
AOA1 (APTX)
AGE OF ONSET 2-10YRS
OCULOMOTOR APRAXIA
DYSTONIA/ CHOREA/ ATAXIA
NEUROPATHY
LAB: ALBUMIN REDUCED/ TOTAL CHOLESTEROL INCREASED
NORMAL FETOPROTEIN
AOA2 (SETX)
AGE OF ONSET 3-30YRS
OCULOMOTOR APRAXIA
DYSTONIA/ CHOREA/ ATAXIA
NEUROPATHY
LAB: ALBUMIN REDUCED/ TOTAL CHOLESTEROL INCREASED
INCREASED IGA/ IGG/ ALPA FETOPROTEIN
FRIEDREICH ATAXIA PHENOTYPE
FRIEDREICH'S ATAXIA (FXN)
ATAXIA/ DYSARTHRIA/ SCOLIOSIS
DIABETES (30%)
HEARING LOSS (20%)
HYPERTROPHIC CARDIOMYOPATHY ARRHYTHMIA/ CHF
LATE ONSET FRIEDREICH'S ATAXIA
(GAA REPEAT X25 GENE)
LOFA 25-40YRS/ VLOFA >40YRS
RETAINED REFLEXES/ SPASTICITY
MRI: CEREBELLAR ATROPHY LATE STAGES
SPINAL CORD ATROPHY
DENTATE IRON ACCUMULATION AND ATROPHY
ABETALIPOPROTEINAEMIA (MTTP)
DIARRHOEA/ VIT-E/ VIT-D/ VIT-K DEFICIENCY
ATAXIA/ PERIPHERAL NEUROPATHY
RETINITIS PIGMENTOSA
ATAXIA WITH VITAMIN E DEFICIENCY (TTPA)
VIT-E DEFICIENCY
TITUBATION
ATAXIA/ PERIPHERAL NEUROPATHY
RETINITIS PIGMENTOSA/ MACULAR ATROPHY
SPASTICITY
CORTICAL
HUNTINGTON DISEASE (HTT 4p16.3)
CHOREA (90%)
PSYCHIATRIC MANIFESTATIONS
PARKINSONISM/ DYSTONIA
ATAXIA/TICS
SPASTICITY CAN BE SEEN
NO FAMILY HISTORY (8%)
BASAL GANGLIA
MONOGENIC PARKINSON'S DISEASE
FBX07
PYRAMIDAL/ PSYCHIATRY
CHOREA/ VSGP
MINERAL DEPOSIT DISORDERS
PKAN (PANK2)
TYPICAL PKAN:
AGE OF ONSET <12YRS
DYSARTHRIA/ DYSTONIA/ OPISTHOTONUS
PRAYING MANTIS SIGN/ CHOREA
PARKINSONISM/ SPASTICITY/ OPTIC ATROPHY
RETINITIS PIGMENTOSA (25%)
ACANTHOCYTES (8%)
ATYPICAL PKAN:
EARLY CHILDHOOD TO LATE ADULTHOOD
SLOWER PROGRESSION
NEUROPSYCHIATRIC MANIFESTATIONS
OCD/ IMPULSIVITY/ DEPRESSION
PALILALIA/ TICS
CAN MIMIC JUVENILE PARKINSONISM
CAN MIMIC TOURETTE SYNDROME
RX: DEFERIPRONE 30MG/KG/DAY
MAY BE USEFUL (MIXED RESULTS)
DBS MAY BE USEFUL
NEUROFERRITINOPATHY
ORO-MANDIBULAR DYSKINESIA (85%)
JAW DYSTONIA/ BLEPHAROSPASM
FOCAL LOWER LIMB CHOREA /DYSTONIA
ACUTE BALLISMUS
LESS COMMON: ATAXIA/ PARKINSONISM/ TICS/TREMOR
LIP-SMACKING/ WRITER'S CRAMP
FRONTAL SUBCORTICAL COGNITIVE DYSFUNCTION
ACERULOPLASMINEMIA
AGE OF ONSET 30-70YRS
OROFACIAL DYSTONIA/ CERVICAL DYSTONIA
COGNITIVE DECLINE/ ATAXIA/ TREMOR/ CHOREA
PARKINSONISM (20%)
DIABETES MELLITUS/ LIVER DYSFUNCTION
RETINAL DEGENERATION
LAB: ABSENT CERULOPLASMIN
HETEROZYGOUS: MODERATELY REDUCED LEVEL
INCREASED FERRITIN
RX: DEFERIPRONE STARTING DOSE 15MG/KG/DAY
TWO DIVIDED DOSES
CAN TITRATE TO MAX 50MG/KG/DAY
PHLEBOTOMY 300ML EVERY 15 DAYS
SENDA (BPAN) (WDR45)
BIPHASIC CLINICAL PROFILE
CHILDHOOD-ONSET:
COGNITIVE DECLINE/RETT-LIKE PHENOTYPE
AUTISM/ STEREOTYPE/ SEIZURES
ADOLESCENCE OR ADULTHOOD ONSET:
SPASTICITY/ PARKINSONISM/ DYSTONIA
RARE CHOREA
OTHER FEATURES:
SEIZURES/ LENNOX GESTAUT SYNDROME
BILATERAL OPTIC ATROPHY
RX: LEVODOPA PARTIALLY RESPONSIVE
SPINAL CORD/ TRACTS
HEREDITARY SPASTIC PARAPARESIS
SPG48 (AP5Z1)
COGNITIVE IMPAIRMENT
CHOREA/ SPASTICITY
SENSORY MOTOR NEUROPATHY
ATAXIA/ DYSTONIA/ PARKINSONISM
THIN CORPUS CALLOSUM
SPG58/ SPAX2 (KIF1C)
CHOREA/ SPASTICITY
ATAXIA/ TREMOR
CERVICAL DYSTONIA
