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

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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

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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

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DYT6 (THAP1)

NECK AND UPPER LIMB DYSTONIA WITH TREMOR

CAN BECOME GENERALIZED

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BIOAMINE DEFECTS

GTPCH1 (AR)

PRESENTATION IN INFANCY

SEIZURES/ INTELLECTUAL DISABILITY

TRUNCAL HYPOTONIA/ LIMB HYPERTONIA

RX: RESPONSIVE TO HIGH-DOSE LEVODOPA

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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 

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TYROSINE HYDROXYLASE - TYPE B

TREMOR/ PTOSIS/ MENTAL RETARDATION

AUTONOMIC DYSFUNCTION

HYPOTONIA/ DELAYED MILESTONES

RX: GOOD LEVODOPA RESPONSE 

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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

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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

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FAHN/ SPG35  

SPASTICITY/ DYSTONIA

OPTIC ATROPHY

COGNITION/ EPILEPSY/ VSGP

MRI: BRAIN STEM ATROPHY

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MPAN  

DYSTONIA/ PARKINSONISM

SPASTICITY

BILATERAL OPTIC ATROPHY

AXONAL NEUROPATHY

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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

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COPAN (COASY)

SLOWLY PROGRESSIVE

DYSTONIA/ PARKINSONISM

SPASTICITY/ AXONAL NEUROPATHY

EYE OF TIGER SIGN 

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VAC14

CHILDHOOD- ADOLESCENCE 

COGNITION

FOCAL DYSTONIA/ PARKINSONISM

ATAXIA/ SPASTICITY

RETINITIS PIGMENTOSA

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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

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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

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WOODHOUSE SAKATI SYNDROME (DCAF17)

SPECTRUM: RAPIDLY DISABLING TO MILD SYMPTOMS

COGNITIVE DECLINE

DEAFNESS/ DYSTONIA

PARKINSONISM/ ATAXIA

ALOPECIA./ DIABETES/ HYPOGONADISM

TRIANGULAR FACE/ HYPERTELORISM

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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

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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

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