CORTICAL/ SUBCORTICAL
COGNITION
HUNTINGTON DISEASE (HTT 4p16.3)
PSYCHIATRIC MANIFESTATIONS
DEMENTIA
CHOREA (90%)/ DYSTONIA
PARKINSONISM/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
DRPLA
<20YS: ATAXIA/ MYOCLONUS
SEIZURES/ CHOREA/ DYSTONIA
>20YRS: ATAXIA/ COGNITION
PSYCHIATRIC MANIFESTATIONS
CHOREA/ DYSTONIA
MRI: CEREBELLAR/ BRAIN STEM ATROPHY
PELIZAEUS MERZBACHER DISEASE (PLP1)
ONSET IN CHILDHOOD
SURVIVAL TILL LATE ADULTHOOD
SPASTIC ATAXIA
SPG2 (PURE SPASTIC PARAPARESIS)
MULTIFOCAL DEMYELINATING NEUROPATHY
COGNITION/ TITUBATION
DYSTONIA/ CHOREA OF EXTREMITIES
HEAD AND UPPER LIMB TREMOR
MRI: HYPOMYELINATION
INTERNAL CAPSULE/ OPTIC RADIATION
PROXIMAL CORONAL RADIATA
CEREBELLAR ATROPHY
RETT SYNDROME
CHOREA/ AUTISM
STEREOTYPE/ HAND WRIGGING
MICROCEPHALY
DECLINE IN SOCIAL LANGUAGE SKILLS 1-4YRS
HYPERVENTILATION
FOXG1 MUTATION
NEURODEVELOPMENTAL DELAY
MICROCEPHALY
CHOREA DYSTONIA/ STEREOTYPE
RX: SOME CASES ARE LEVODOPA RESPONSIVE
ELAC2 MUTATION
CHILDHOOD/ RARELY ADULT ONSET
DELAYED PSYCHOMOTOR DEVELOPMENT
MITOCHONDRIAL DISORDER
CHOREA/ DYSTONIA
BILATERAL HEARING LOSS
HYPERTROPHIC CARDIOMYOPATHY
LAB: ACANTHOCYTES
NEUROACANTHROCYTOSIS
CHOREA-ACANTHOCYTOSIS (VPS13A)
AGE OF ONSET 20-60YRS
ACTION TONGUE DYSTONIA
FEEDING DYSTONIA/ TICS
PARKINSONISM (MAYBE PRESENTING SIGN)
RUBBER-MAN GAIT (KNEE AND HIP BUCKING)
DROP ATTACK
NEUROPATHY/ MYOPATHY
PSYCHIATRIC MANIFESTATIONS/ SEIZURE
HEPATO-SPLEENOMEGALY
LAB: CPK/ LFT ELEVATED
ACANTHOCYTES TO BE SEEN IN 1:1 DILUTION IN NORMAL SALINE WITH PHASE CONTRAST MICROSCOPE
ACANTHOCYTE CAN BE ABSENT
MCLEOD (XK)
COGNITION/ CHOREA
PSYCHITRIC SYMPTOMS/ SEIZURES
NEUROPATHY/ MYOPATHY
CHF/ ATRIAL FIBRILLATION
HAEMOLYSIS
MRI: CAUDATE/ PUTAMEN ATROPHY
WHITE MATTER HYPERINTENSITIES
CEREBELLAR/ AFFERENTS
ATAXIA WITH OCULOMOTOR APRAXIA
ATAXIA TELANGIECTASIA
TELENGIECTASIA OVER EYES
AND SUN EXPOSED AREAS
OCULOMOTOR APRAXIA
DYSTONIA/ CHOREA/ MYOCLONUS
PARKINSONISM/ ATAXIA
TREMOR/ NEUROPATHY
LYMPHOMA/ LEUKEMIA, EARLY
SOLID TUMOUR, LATE
LAB: LOW IGA/ IGG LEVELS
AOA1 (APTX)
AGE OF ONSET 2-10YRS
OCULOMOTOR APRAXIA
DYSTONIA/ CHOREA/ ATAXIA
NEUROPATHY
LAB: ALBUMIN REDUCED
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
MITOCHONDRIAL
MELAS
MYOPATHY/ ENCEPHALOPATHY
STROKE LIKE EPISODES
NON-OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY
LEIGH SYNDROME
MITOCHONDRIAL/ NUCLEAR GENES INVOLVED IN OXIDATIVE PHOSPHORYLATION (COMPLEX 1-4)
COGNITION/ ATAXIA/ CHOREA
OPTIC ATROPHY/ RETINITIS PIGMENTOSA
STRABISMUS/ OPHTHALMOPARESIS
NEUROPATHY/ MYOPATHY
SHORT STATURE/ CARDIOMYOPATHY
ADULT ONSET SUBACUTE NECROTIZING ENCEPHALOPATHY VARIANT:
VISION PROBLEM/ ATAXIA
BASAL GANGLIA
MINERAL DEPOSITION 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
RX: LEVODOPA PARTIALLY RESPONSIVE
FAHN/ SPG35
SPASTICITY/ DYSTONIA
OPTIC ATROPHY
COGNITION/ EPILEPSY
VSGP
BRAIN STEM ATROPHY
MPAN
DYSTONIA/ PARKINSONISM
SPASTICITY
BILATERAL OPTIC ATROPHY
AXONAL NEUROPATHY
SENDA (BPAN) (WDR45)
BIPHASIC CLINICAL PROFILE
CHILDHOOD-ONSET:
COGNITIVE DECLINE/RETT-LIKE PHENOTYPE
AUTISM/ STEREOTYPE/ SEIZURES
ADOLESCENCE OR ADULTHOOD ONSET:
SPASTICITY/ PARKINSONISM/ DYSTONIA
OTHER FEATURES:
SEIZURES/ LENNOX GESTAUT SYNDROME
BILATERAL OPTIC ATROPHY
RX: LEVODOPA PARTIALLY RESPONSIVE
COPAN (COASY)
SLOWLY PROGRESSIVE
DYSTONIA/ PARKINSONISM
SPASTICITY/ AXONAL NEUROPATHY
MRI: EYE OF TIGER SIGN
VAC14 MUTATIONS
AGE OF ONSET 6-15YRS
COGNITION
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
FAHR'S 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
WOODHOUSE SAKATI SYNDROME (DCAF17)
SPECTRUM: RAPIDLY DISABLING TO MILD SYMPTOMS
COGNITIVE DECLINE
DEAFNESS/ DYSTONIA
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
LYSOSOMAL
NIEMANN PICK C DISEASE
VSGP/ GELASTIC CATAPLEXY
ATAXIA/ DYSTONIA/ CHOREA
HEPATOSPLENOMEGALY
THROMBOCYTOPENIA
AMINO-ORGANIC ACIDURIA
LESCH NYHAN SYNDROME
DYSARTHRIA/ DYSTONIA/ TICS
ARTHRITIS/ SELF MUTILATION
GLUTARIC ACIDURIA (GCDH)
COGNITION/ ATAXIA/ DYSTONIA
LAB: URINE ORGANIC ACID
MRI: OPEN OPERCULA/ SDH/ WMH
BASAL GANGLIA HYPERINTENSITY (T2)
RX: LOW LYSINE DIET/ CARNITINE SUPPLEMENT
PAROXYSMAL
GLUT1 (SLC2A1)
CHILDHOOD - ADULT-ONSET
10% DON'T HAVE MUTATION IN SLC2A1
PAROXYSMAL/ FIXED
PED/ PNKD/ EPISODIC ATAXIA
RESISTANT EPILEPSY/ MR
DYSTONIA/ ATAXIA
CRISS CROSS GAIT/ SPASTICITY
WEAKNESS/HEADACHE/ VOMITING
TRIGGERS: FAST/INFECTIONS
VITAMIN DEFECTS
BT-BGD (SLC19A3)
<6Y : INFANTILE SPASM
6-15 : DYSTONIA/ ATAXIA/ CHOREA
>15 : WERNICKE LIKE
MRI: BASAL GANGLIA T2 HYPERINTENSITY
RX: BIOTIN 5-20MG/ DAY
THIAMINE 300-900MG /DAY
PAROXYSMAL DISORDERS
STATIC/ MILD
ADCY5
AGE OF ONSET 1-20YRS
MYOCLONUS/DYSTONIA/CHOREA
CAN BE MILD/ STATIC
AXIAL HYPOTONIA/ FACIAL MYOKYMIA
FROG LIKE GAIT/ OCULOMOTOR APRAXIA
VERTICAL SACCADES ABNORMALITY
DROWSY/ BALLISTIC DYSTONIA (PAINFUL)
RX: CAFFEINE / ACETAZOLAMIDE
CLONAZEPAM/ DBS
PDE10A
AGE OF ONSET 5-15YRS
CHOREA
DIURNAL VARIATION
BENIGN HEREDITARY CHOREA
(NKX2-1/TITF1)
LUNG: OBSTRUCTIVE/ INTERSTITIAL LUNG DISEASE/ RECURRENT INFECTIONS
THYROID: CONGENITAL HYPOTHYROIDISM
BRAIN: CHOREA/ MYOCLONUS/ DYSTONIA
ATAXIA/ HYPOTONIA
OCD/ ADHD/ PSYCHOSIS
OTHER: WEB NECK/ SHORT STATURE
JOINT HYPER-MOBILITY
MRI: CYSTIC CHANGES IN PITUITARY
PRRT2
SECONDS TO MINS DURATION
LIMBS > NECK OR FACE
BENIGN FAMILIAL INFANTILE EPILEPSY
INFANTILE CONVULSIVE
CHOREATHETOSIS (ICCA)
ABSENCE SEIZURE
PAROXYSMAL TORTICOLLIS
EPISODIC ATAXIA/ PED
TRIGGERS: STARTLE/ HYPERVENTILATION/ EXERCISE
RX: CARBAMAZEPINE
MENTAL RETARDATION/ SEIZURES
GNAO1
PAROXYSMAL DYSTONIA/ CHOREA
PKD
MENTAL RETARDATION/ FOCAL SEIZURES
GRIN1
MENTAL RETARDATION/ SEIZURES
CHOREA/ DYSTONIA
GPR88
AGE OF OSNET 8-10YRS
SPEECH DELAY/ LEARNING DISABILITY
GNAO1
PAROXYSMAL DYSTONIA/ CHOREA/ PKD
MENTAL RETARDATION/ FOCAL SEIZURES
GNB1
SIMILAR TO GNAO1
PAROXYSMAL DYSTONIA/ CHOREA
PROLONGED EPISODES
DYSTONIA MYOCLONUS / STEREOTYPE
MICROCEPHALY
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SYSTEMIC
TUBEROUS SCLEROSIS
BEHAVIORAL PROBLEM SEIZURES
CHOREA DUE TO INRACRANIAL TUBERS
HYPOPIGMENTED PATCH
ANGIOFIBROMA
SUBEPENDYMAL CALCIFICATIONS
ELAC2 MUTATION
CHILDHOOD/ RARELY ADULT ONSET
DELAYED PSYCHOMOTOR DEVELOPMENT
MITOCHONDRIAL DISORDER
CHOREA/ DYSTONIA
BILATERAL HEARING LOSS
HYPERTROPHIC CARDIOMYOPATHY
LAB: ACANTHOCYTES