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OCULOGYRIC CRISIS
DOPAMINE BIO AMINE DEFECTS
GTPCH1 (AR)
PRESENTATION IN INFANCY
SEIZURES/ INTELLECTUAL DISABILITY
TRUNCAL HYPOTONIA/ LIMB HYPERTONIA
RX: RESPONSIVE TO HIGH-DOSE LEVODOPA
GTPCH1 (AD)
CAN PRESENT AT LATER AGE
EARLY ONSET FOOT DYSTONIA (EQUINOVARUS)
OCCASIONALLY, UL DYSTONIA/ TREMOR
LATER PARKINSONISM WITH POSTURAL TREMOR
OCD/ SPASTICITY/ SCOLIOSIS
DIURNAL FLUCTUATIONS
PHENOTYPES:
BENIGN PARKINSONISM
FOOT DYSTONIA
MYOCLONUS DYSTONIA
SPASTIC PARAPARESIS
RX: EXCELLENT RESPONSE TO LEVODOPA
TYROSINE HYDROXYLASE - TYPE A
CEREBRAL PALSY/ JUVENILE PARKINSONISM
OGC/ UPPER LIMB DYSTONIA
AUTONOMIC DYSFUNCTION
RX: GOOD LEVODOPA RESPONSE
TYROSINE HYDROXYLASE - TYPE B
TREMOR/ PTOSIS/ MENTAL RETARDATION
AUTONOMIC DYSFUNCTION
HYPOTONIA/ DELAYED MILESTONES
RX: GOOD LEVODOPA RESPONSE
SEPIAPTERIN REDUCTASE DEFICIENCY
MICROCEPHALY
MENTAL RETARDATION/ PARKINSONISM
OGC/ AUTONOMIC DYSFUNCTION
HYPOTONIA/ SPASTICITY
RX: HIGH DOSE OF LEVODOPA
PTP SYNTHASE DEFICIENCY (PTPS)
HYPERPHENYLALANINEMIA
DYSTONIA/ EPILEPSY
HYPOTONIA/ OPHISTOTONUS
RIGIDITY/ CHOREA
RX: EXCELLENT LEVODOPA RESPONSE
AADC DEFICIENCY
PHENOTYPES:
SPASTIC DIPLEGIA LIKE CP
SPASTIC PARAPLEGIA
FOCAL DYSTONIA
RIGIDITY/ BRADYKINESIA
PAROXYSMAL MOVEMENT DISORDERS
INFANTILE ONSET:
HYPOTONIA
MIMIC NEUROMUSCULAR DISEASE
RIGIDITY/ MULTIFOCAL MYOCLONUS
OCULOGYRIC CRISIS
DIURNAL OR WEEKLY FLUCTUATIONS
RX: DOPAMINE AGONIST/ MAO INHIBITORS
PYRIDOXINE 100-200MG/DAY
FOLIC ACID
TRANSPORTOPATHIES
VMAT2 DEFICIENCY (SLC18A2)
INFANTILE DYSTONIA PARKINSONISM
AUTONOMIC INSTABILITY
RX: DOPAMINE AGONIST
LEVODOPA WORSENS SYMPTOMS
DOPAMINE TRANSPORTER DEFICIENCY SYNDROME (SLC6A3)
TYPICAL: INFANTILE
ATYPICAL: ADULT-ONSET
PARKINSONISM/ DYSTONIA
OCULOGYRIC CRISIS/ OCULAR FLUTTER
SACCADIC INITIATION PROBLEM
AUTONOMIC DYSFUNCTION
PAROXYSMAL UPGAZE
NORMAL VARIANT
AGE < 2YRS
GRID2
ATAXIA
CACNA1
EPISODIC ATAXIA
OROMANDIBULAR DYSTONIA
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-SPLEENOMEGALY
LAB: CPK/ LFT ELEVATED
ACANTHOCYTES TO BE SEEN IN 1:1 DILUTION IN NORMAL SALINE WITH PHASE CONTRAST MICROSCOPE
ACANTHOCYTE CAN BE ABSENT
DYT3 (TAF1)
PARKINSONISM
ONLY MALES AFFECTED
X-LINKED RECESSIVE
JAW AND NECK DYSTONIA COMMON
LATER BECOME GENERALIZED
UL DYSTONIA (LESS COMMON)
DYT6 (THAP1)
AGE OF ONSET 5-38YRS
NECK AND UPPER LIMB DYSTONIA
UPPER LIMB TREMOR
DYSPHONIA
DYT24 (ANO3)
ESSENTIAL TREMOR PHENOTYPE
CRANIOCERVICAL DYSTONIA
FAST MYOCLONUS
DYT25 (GNAL)
AGE OF ONSET 7-54 YRS
CERVICAL/ CRANIAL DYSTONIA
OROMANDIBULAR/ LARYNX
TREMOR
KMT2B
MEAN AGE OF ONSET 7 YRS
LOWER LIMB ONSET/ GENERALIZED
PROMINENT OMD AND CERVICAL DYSTONIA/OPHISTOTONUS
MENTAL RETARDATION
SENSORINEURAL HEARING LOSS
ELONGATED FACE/ BULBOUS NASAL TIP
MISSENSE VARIANT—LATE PRESENTATION
RX: DBS USEFUL
SCP2 MUTATIONS
FOCAL OMD/ TORTICOLLIS
ATAXIA/ DYSTONIA/ MOTOR NEUROPATHY
MRI: CEREBRAL/ PONS WHITE MATTER HYPERINTENSITY
BASAL GANGLIA IRON DEPOSITION
BRAIN MINERALIZATION DISORDERS
WILSON DISEASE
LIVER/ NEUROLOGICAL/ PSYCHIATRY
DYSTONIA/ CHOREA/ PARKINSONISM
DEPRESSION/ OCD/ PHOBIAS
PROTEINURIA/ ARTHRITIS/SUNFLOWER CATARACT
CARDIOMYOPATHY/ ARRHYTHMIAS
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
LYSOSOMAL
GM1 GANGLIOSIDOSIS
TYPE 1 (INFANTILE)
COGNITION/ SEIZURES
CORNEAL OPACITY
TYPE 2 (JUVENILE)
COGNITION/ DYSTONIA
ORGANOMEGALY/ CHERRY RED SPOT
TYPE 3 (ADULT)
DYSTONIA/ SPINAL BONY ABNORMALITY
ANGIOKERATOMA (TRUNK)
LIKE IN FABRY'S DISEASE
LESCH-NYHAN SYNDROME
ARTHRITIS/ SELF MUTILATION
AUTOIMMUNE
RI AB
AGE OF ONSET >40YRS
SUBACUTE ONSET PARKINSONISM
JAW CLOSING DYSTONIA
PSP PHENOTYPE
OCULOPALATAL-MYOCLONUS
NEOPLASIA: BREAST/ OVARY
METABOLIC
DRUGS
DYSARTHRIA + ANARTHRIA
GM1 GANGLIOSIDOSIS
TYPE 1 (INFANTILE)
COGNITION/ SEIZURES
CORNEAL OPACITY
TYPE 2 (JUVENILE)
COGNITION/ DYSTONIA
ORGANOMEGALY/ CHERRY RED SPOT
TYPE 3 (ADULT)
DYSTONIA/ SPINAL BONY ABNORMALITY
ANGIOKERATOMA (TRUNK)
LIKE IN FABRY'S DISEASE
NIEMANN PICK C DISEASE
VSGP/ GELASTIC CATAPLEXY
ATAXIA/ DYSTONIA/ CHOREA
PARKINSONISM
HEPATOSPLEENOMEGALY
THROMBOCYTOPENIA
LESCH-NYHAN SYNDROME
ARTHRITIS/ SELF MUTILATION
AADC DEFICIENCY
PHENOTYPES:
SPASTIC DIPLEGIA LIKE CP
SPASTIC PARAPLEGIA
FOCAL DYSTONIA
RIGIDITY/ BRADYKINESIA
PAROXYSMAL MOVEMENT DISORDERS
INFANTILE ONSET:
HYPOTONIA
MIMIC NEUROMUSCULAR DISEASE
RIGIDITY/ MULTIFOCAL MYOCLONUS
OCULOGYRIC CRISIS
DIURNAL OR WEEKLY FLUCTUATIONS
RX: DOPAMINE AGONIST/ MAO INHIBITORS
PYRIDOXINE 100-200MG/DAY
FOLIC ACID
H-ABC/ DYT4 (TUBB4)
HYPOMYELINATION WITH ATROPHY OF BASAL GANGLIA NAD CEREBELLUM
DYSTONIA/ ATAXIA/ COGNITION
WHISPERING DYSPHONIA
MICROCEPHALY/ SPASTICITY
DYT6 (THAP1)
AGE OF ONSET 5-38YRS
NECK AND UPPER LIMB DYSTONIA
UPPER LIMB TREMOR
DYSPHONIA
ROPD/ DYT12 (ATP1A3)
AGE OF ONSET 4- 55 YRS
DYSTONIA WITH PARKINSONISM OVER DAYS TO WEEKS
ABRUPT ONSET THEN STABILIZES
MILD IMPROVEMENT POSSIBLE
TRIGGER: FEVER/ STRESS/ ALCOHOL
RX: POOR LEVODOPA RESPONSE
DYT16 (PRKRA)
PROMINENT BULBAR SYMPTOMS
BECOMES GENERALIZED
WILSON DISEASE
LIVER/ NEUROLOGICAL/ PSYCHIATRY
DYSTONIA/ CHOREA/ PARKINSONISM
DEPRESSION/ OCD/ PHOBIAS
PROTEINURIA/ ARTHRITIS/SUNFLOWER CATARACT
CARDIOMYOPATHY/ ARRYTHMIAS
PKAN (PANK2)
TYPICAL PKAN:
AGE OF ONSET <12YRS
DYSARTHRIA/ DYSTONIA/ OPHISTOTONUS
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
SLC30A10
MANGANESE TRANSPORTER
SPASTICITY/ FINE TREMORS
MEIG SYNDROME (PRIMARY)
H-ABC/ DYT4 (TUBB4)
HYPOMYELINATION WITH ATROPHY OF BASAL GANGLIA AND CEREBELLUM
DYSTONIA/ ATAXIA/ COGNITION
WHISPERING DYSPHONIA
MICROCEPHALY/ SPASTICITY
DYT6 (THAP1)
AGE OF ONSET 5-38YRS
NECK AND UPPER LIMB DYSTONIA UPPER LIMB TREMOR
DYSPHONIA
DYT24 (ANO3)
ESSENTIAL TREMOR PHENOTYPE
CRANIOCERVICAL DYSTONIA
FAST MYOCLONUS
DYT25 (GNAL)
AGE OF ONSET 7-54 YRS
CERVICAL/ CRANIAL DYSTONIA
OROMANDIBULAR/ LARYNX
TREMOR
KMT2B
MEAN AGE OF ONSET 7 YRS
LOWER LIMB ONSET/ GENERALIZED
PROMINENT OMD AND CERVICAL DYSTONIA/OPHISTOTONUS
MENTAL RETARDATION
SENSORINEURAL HEARING LOSS
ELONGATED FACE/ BULBOUS NASAL TIP
MISSENSE VARIANT—LATE PRESENTATION
RX: DBS USEFUL
ADULT FOCAL DYSTONIA
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
PARKINSONISM/ ATAXIA
ALOPECIA./ DIABETES/ HYPOGONADISM
TRIANGULAR FACE/ HYPERTELORISM
SCP2 MUTATIONS
FOCAL OMD/ TORTICOLLIS
ATAXIA/ DYSTONIA/ MOTOR NEUROPATHY
MRI: CEREBRAL/ PONS WHITE MATTER HYPERINTENSITY
BASAL GANGLIA IRON DEPOSITION
BRAIN MINERALIZATION DISORDER
KUFOR RAKEB SYNDROME (ATP13A2)
PARK9/ SPG78
COGNITION/ PARKINSONISM/ VSGP
VISUAL HALLUCINATION
OCULOGYRIC CRISIS
SPG78: LATE SPASTICITY WITHOUT PARKINSONISM
FACIAL-FAUCIAL-FINGER-MYOCLONUS
PRIMARY DYTONIA
ROPD/ DYT12 (ATP1A3)
AGE OF ONSET 4- 55 YRS
DYSTONIA WITH PARKINSONISM OVER DAYS TO WEEKS
ABRUPT ONSET THEN STABILIZES
MILD IMPROVEMENT POSSIBLE
TRIGGER: FEVER/ STRESS/ ALCOHOL
RX: POOR LEVODOPA RESPONSE
PAROXYSMAL
GLUT1 (SLC2A1)
CHILD - ADULT ONSET
MUTATION IN SLC2A1 (90%)
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 PHENOTYPE
AUTOIMMUNE
NMDA ENCEPHALITIS
OTHER
PERRY
VSGP/ HYPOVENTILATION
CHEDIAK HIGASHI (LYST)
AGE OF ONSET 20-40YRS
LYSOSOMAL TRAFFIC REGULATOR PROTEIN
ALBINISM/ INFECTIONS/ BLEEDING/
PARTIAL ALBINISM/ OCULAR ALBINISM
PARKINSONISM/ DYSTONIA/ ATAXIA/ NEUROPATHY
RETT SYNDROME (MECPS)
FEMALES AFFECTED MORE
CHOREA/ AUTISM/ STEREOTYPE
HAND WRIGGING/ CLAPPING/ RUBBING
MICROCEPHALY
NORMAL TILL 6-18 MONTHS
HYPERVENTILATION
MIDBRAIN/BG INFARCTS
PRIMARY BLEPHAROSPASM
NONE OF THESE GENES CAUSE PURE BLEPHAROSPASM
GNAL
CIZ1
TOR1A
ANO3
TUBB4A
DRD5 (DOPAMINE RECEPTOR TYPE D5)
LOWER LIMB ONSET
DYT1 (TORIA)
AGE OF ONSET: 4-64 YRS
INITIALLY ACTION SPECIFIC DYSTONIA
LATER: REST DYSTONIA
WALKING/ WRITING
START IN THE LEG AND THEN INVOLVE THE ARMS
FOOT INVERSION/ EVERSION
KNEE/ HIP FLEXION
DYSTONIC LEG / ARM TREMOR
PHENOTYPES:
BLEPHAROSPASM
WRITER'S CRAMP (LATE-ONSET DYT1)
FOCAL DYSTONIA IN 20%
FLUCTUATING UNILATERAL DYSTONIA MYOCLONUS
GENERALIZED DYSTONIA
GTPCH1 (AD)
CAN PRESENT AT LATER AGE
EARLY ONSET FOOT DYSTONIA (EQUINOVARUS)
OCCASIONALLY, UL DYSTONIA/ TREMOR
LATER PARKINSONISM WITH POSTURAL TREMOR
OCD/ SPASTICITY/ SCOLIOSIS
DIURNAL FLUCTUATIONS
PHENOTYPES:
BENIGN PARKINSONISM
FOOT DYSTONIA
MYOCLONUS DYSTONIA
SPASTIC PARAPARESIS
RX: EXCELLENT RESPONSE TO LEVODOPA
DYT16 (PRKRA)
DYSTONIA/ PARKINSONISM
PROMINENT BULBAR
RX: GPI DBS MAY BE USEFUL
KMT2B
MEAN AGE OF ONSET 7 YRS
LOWER LIMB ONSET/ GENERALIZED
PROMINENT OMD AND CERVICAL DYSTONIA/OPISTHOTONUS
MENTAL RETARDATION
SENSORINEURAL HEARING LOSS
ELONGATED FACE/ BULBOUS NASAL TIP
MISSENSE VARIANT—LATE PRESENTATION
RX: DBS USEFUL
ACERULOPLASMINEMIA
AGE OF ONSET 30-70YRS
OROFACIAL DYSTONIA/ CERVICAL DYSTONIA
COGNITIVE DECLINE/ ATAXIA
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
BRUXISM (DYSTONIA/ AKATHISIA)
ANTI DOPAMINERGIC
SNRI
SSRI
YOUNG CERVICAL DYSTONIA
DYT6 (THAP1)
AGE OF ONSET 5-38YRS
NECK AND UPPER LIMB DYSTONIA UPPER LIMB TREMOR
DYSPHONIA
DYT23 (CIZ1)
CERVICAL DYSTONIA
NECK TREMOR
ESSENTIAL TREMOR PHENOTYPE
DYT24 (ANO3)
ESSENTIAL TREMOR PHENOTYPE
CRANIOCERVICAL DYSTONIA
FAST MYOCLONUS
DYT25 (GNAL)
AGE OF ONSET 7-54 YRS
CERVICAL/ CRANIAL DYSTONIA
OROMANDIBULAR/ LARYNX
TREMOR
ATAXIA TELANGIECTASIS
CERVICAL DYSTONIA
RX: LEVODOPA
KMT2B
MEAN AGE OF ONSET 7 YRS
LOWER LIMB ONSET/ GENERALIZED
PROMINENT OMD AND CERVICAL DYSTONIA/OPHISTOTONUS
MENTAL RETARDATION
SENSORINEURAL HEARING LOSS
ELONGATED FACE/ BULBOUS NASAL TIP
MISSENSE VARIANT—LATE PRESENTATION
RX: DBS USEFU
ATAXIA WITH VITAMIN E DEFICIENCY (TTPA)
VIT-E DEFICIENCY
TITUBATION
ATAXIA/ PERIPHERAL NEUROPATHY
RETINITIS PIGMENTOSA/ MACULAR ATROPHY
GENERALISED DYSTONIA
PRIMARY DYSTONIA
DYT1 (TORIA)
AGE OF ONSET: 4-64 YRS
INITIALLY ACTION SPECIFIC DYSTONIA
LATER: REST DYSTONIA
WALKING/ WRITING
START IN THE LEG AND THEN INVOLVE THE ARMS
FOOT INVERSION/ EVERSION
KNEE/ HIP FLEXION
DYSTONIC LEG / ARM TREMOR
PHENOTYPES:
BLEPHAROSPASM
WRITER'S CRAMP (LATE ONSET DYT1)
FOCAL DYSTONIA IN 20%
GENERALIZED DYSTONIA
DYT3 (TAF1)
PARKINSONISM
ONLY MALES AFFECTED
X-LINKED RECESSIVE
JAW AND NECK DYSTONIA COMMON
LATER BECOME GENERALIZED
UL DYSTONIA (LESS COMMON)
DYT16 (PRKRA)
PROMINENT BULBAR
BECOMES GENERALIZED
KMT2B
MEAN AGE OF ONSET 7 YRS
LOWER LIMB ONSET/ GENERALIZED
PROMINENT OMD AND CERVICAL DYSTONIA/OPISTHOTONUS
MENTAL RETARDATION
SENSORINEURAL HEARING LOSS
ELONGATED FACE/ BULBOUS NASAL TIP
MISSENSE VARIANT—LATE PRESENTATION
RX: DBS USEFUL
DYT6 (THAP1)
NECK AND UPPER LIMB DYSTONIA WITH TREMOR
CAN BECOME GENERALIZED
BIOAMINE DEFECTS
GTPCH1 (AR)
PRESENTATION IN INFANCY
SEIZURES/ INTELLECTUAL DISABILITY
TRUNCAL HYPOTONIA/ LIMB HYPERTONIA
RX: RESPONSIVE TO HIGH-DOSE LEVODOPA
GTPCH1 (AD)
CAN PRESENT AT LATER AGE
EARLY ONSET FOOT DYSTONIA (EQUINOVARUS)
OCCASIONALLY, UL DYSTONIA/ TREMOR
LATER PARKINSONISM WITH POSTURAL TREMOR
OCD/ SPASTICITY/ SCOLIOSIS
DIURNAL FLUCTUATIONS
PHENOTYPES:
BENIGN PARKINSONISM
FOOT DYSTONIA
MYOCLONUS DYSTONIA
SPASTIC PARAPARESIS
RX: EXCELLENT RESPONSE TO LEVODOPA
TYROSINE HYDROXYLASE - TYPE A
CEREBRAL PALSY/ JUVENILE PARKINSONISM
OGC/ UPPER LIMB DYSTONIA
AUTONOMIC DYSFUNCTION
RX: GOOD LEVODOPA RESPONSE
TYROSINE HYDROXYLASE - TYPE B
TREMOR/ PTOSIS/ MENTAL RETARDATION
AUTONOMIC DYSFUNCTION
HYPOTONIA/ DELAYED MILESTONES
RX: GOOD LEVODOPA RESPONSE
BRAIN MINERALIZATION 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
MRI: 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
EYE OF TIGER SIGN
VAC14
CHILDHOOD- ADOLESCENCE
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
PARKINSONISM/ ATAXIA
ALOPECIA./ DIABETES/ HYPOGONADISM
TRIANGULAR FACE/ HYPERTELORISM
KUFOR RAKEB SYNDROME (ATP13A2)
PARK9/ SPG78
COGNITION/ PARKINSONISM/ VSGP
VISUAL HALLUCINATION
LEVODOPA-INDUCED DYSKINESIA
OCULOGYRIC CRISIS
FACIAL-FAUCIAL-FINGER-MYOCLONUS
SPG78: LATE SPASTICITY WITHOUT PARKINSONISM
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
YOUNG WRITERS CRAMP
DYT1 (TORIA)
AGE OF ONSET: 4-64 YRS
INITIALLY ACTION SPECIFIC DYSTONIA
LATER: REST DYSTONIA
WALKING/ WRITING
START IN THE LEG AND THEN INVOLVE THE ARMS
FOOT INVERSION/ EVERSION
KNEE/ HIP FLEXION
DYSTONIC LEG / ARM TREMOR
PHENOTYPES:
BLEPHAROSPASM
WRITER'S CRAMP (LATE-ONSET DYT1)
FOCAL DYSTONIA IN 20%
FLUCTUATING UNILATERAL DYSTONIA MYOCLONUS
GENERALIZED DYSTONIA
DYT3 (TAF1)
PARKINSONISM
ONLY MALES AFFECTED
X-LINKED RECESSIVE
JAW AND NECK DYSTONIA COMMON
LATER BECOME GENERALIZED
UL DYSTONIA (LESS COMMON)
DYT11 (SGCE)
AGE OF ONSET <20 YRS
HEAD/ ARM/ UPPER BODY MYOCLONUS
OCD/ ANXIETY
RX: CLONAZEPAM/ VALPROIC ACID
TRIHEXYPHENIDYL
THALAMIC DBS
GM1 GANGLIOSIDOSIS
TYPE 1 (INFANTILE)
COGNITION/ SEIZURES
CORNEAL OPACITY
TYPE 2 (JUVENILE)
COGNITION/ DYSTONIA
ORGANOMEGALY/ CHERRY RED SPOT
TYPE 3 (ADULT)
DYSTONIA/ SPINAL BONY ABNORMALITY
ANGIOKERATOMA (TRUNK)
LIKE IN FABRY'S DISEASE
GLUT1 (SLC2A1)
CHILD - ADULT-ONSET
PAROXYSMAL/ FIXED
PED/ PNKD/ EPISODIC ATAXIA
RESISTANT EPILEPSY/ MR
DYSTONIA/ ATAXIA
CRISS CROSS GAIT/ SPASTICITY
L2-HYDROXY-GLUTARIC ACIDURIA
MACROCEPHALY
HIGH RISK OF MALIGNANCY
SPASTICITY/ ATAXIA/ DYSTONIA
PARKINSONISM
MRI: HYPERINTENSITY (T2/ FLAIR)
CAUDATE/ PUTAMEN
GLOBUS PALLIDUS/ DENTATE
CENTRIPETAL WHITE MATTER
U-FIBRE INVOLVED FIRST
CEREBELLAR WHITE MATTER
MACROCEPHALY
ABNORMAL DAT SCAN
RX: LEVODOPA/ RIBOFLAVIN
CAN PRESENT AS WRITERS CRAMP
COQ10 DEFICIENCY (ADCK3/ARCA2)
ATAXIA/DYSTONIA
NEUROFERRITINOPATHY
ORO-MANDIBULAR DYSKINESIA (85%)
JAW DYSTONIA/ BLEPHAROSPASM
FOCAL LOWER LIMB CHOREA /DYSTONIA
ACUTE BALLISMUS
LESS COMMON: ATAXIA/ PARKINSONISM/ TICS/TREMOR
RARELY: WRITER'S CRAMP
LIP-SMACKING/ WRITER'S CRAMP
FRONTAL SUBCORTICAL COGNITIVE DYSFUNCTION
DYSTONIC TREMOR UPPER LIMBS
DYT6 (THAP1)
AGE OF ONSET 5-38YRS
NECK AND UPPER LIMB DYSTONIA UPPER LIMB TREMOR
DYSPHONIA
DYT23 (CIZ1)
CERVICAL DYSTONIA
NECK TREMOR
ESSENTIAL TREMOR PHENOTYPE
DYT24 (ANO3)
ESSENTIAL TREMOR PHENOTYPE
CRANIOCERVICAL DYSTONIA
FAST MYOCLONUS
DYT25 (GNAL)
AGE OF ONSET 7-54 YRS
CERVICAL/ CRANIAL DYSTONIA
OROMANDIBULAR/ LARYNX
TREMOR