CORTICAL/ SUBCORTICAL
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
PARTINGTON SYNDROME (ARX)
X-LINKED RECESSIVE
ONSET NFANCY/CHILDHOOD
MENTAL RETARDATION/ DYSTONIA
GAUCHER DISEASE (GBA)
GD1: ADULT GD
VARIED AGE PRESENTATION
COGNITION/ PARKINSONISM
TREMOR/ ATAXIA
INCREASED RISK FOR PD (10x)
POOR RESPONSE TO LEVODOPA
NO EYE MOVEMENT ABNORMALITY
ACUTE PAINFUL BONE CRISIS
LAB: ANAEMIA/ PANCYTOPENIA
THROMBOCYTOPENIA
HEPATOSPLENOMEGALY
GD3: JUVENILE GD
AGE OF ONSET <10 YRS
HSGP (EARLY) / VSGP (LATE)
CONVERGENT SQUINT (VI NERVE PALSY)
COGNITION/ EPILEPSY/
PROGRESSIVE MYOCLONIC EPILEPSY
FACE/ LIMB DYSTONIA
ATAXIA/ SPASTICITY
PELIZAEUS MERZBACHER (PLP1)
SPASTIC ATAXIA
SPG2: PURE SPASTIC PARAPARESIS
MULTIFOCAL DEMYELINATING NEUROPATHY
COGNITION/ TITUBATION
DYSTONIA/ CHOREA OF EXTREMITIES
HEAD AND UPPER LIMB TREMOR
SURVIVAL TILL LATE ADULTHOOD
MRI: HYPOMYELINATION
INTERNAL CAPSULE/ OPTIC RADIATION
PROXIMAL CORONAL RADIATA
CEREBELLAR ATROPHY
BASAL GANGLIA
LYSOSOMAL (BG)
NIEMANN PICK C DISEASE
VSGP/ GELASTIC CATAPLEXY
ATAXIA/ DYSTONIA/ CHOREA
HEPATOSPLEENOMEGALY
THROMBOCYTOPENIA
GM1 GANGLIOSIDOSIS
TYPE 3 (ADULT)
DYSTONIA/ PARKINSONISM
WRITERS CRAMP
DYSTONIA/ SPINAL BONY ABNORMALITY
ANGIOKERATOMA (TRUNK) LIKE IN FABRY'S DISEASE
PRIMARY DYSTONIA
H-ABC/ DYT4 (TUBB4)
HYPOMYELINATION WITH ATROPHY OF BASAL GANGLIA NAD CEREBELLUM
DYSTONIA/ ATAXIA/ COGNITION
WHISPERING DYSPHONIA
MICROCEPHALY/ SPASTICITY
AMINOACIDURIA
L2 H-GLUTARIC ACIDURIA
MACROCEPHALY
HIGH RISK OF MALIGNANCY
SPASTICITY/ ATAXIA/ DYSTONIA
IMAGING: ABNORMAL DAT SCAN
RX: LEVODOPA/ RIBOFLAVIN
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
>15 : WERNICKE LIKE PHENOTYPE
SYSTEMIC
AICARDI GOUTIERES DISEASE
(AGS 17 / TREX1/IFIH1)
CHILBLAINS
ENCEPHALOPATHY/ MICROCEPHALY
GENERALIZED DYSTONIA
MRI: SYMMETRICAL BASAL GANGLIA
AND BRAIN CALCIFICATIONS
RX: STN DBS MAY BEUSEFUL
CEREBELLUM/ CEREBELLAR AFFERENTS
SCA 17 (TBP CAG REPEAT)
PSYCHIATRIC SYMPTOMS/ DEMENTIA
ATAXIA/ SPASTICITY/ CHOREA
PARKINSONISM
AUTONOMIC DYSFUNCTION
SUPRANUCLEAR GAZE PALSY
PHENOTYPE
PSP/ MSA/ HUNTINGTON'S DISEASE
SCA48/ SCAR16 (STUB1)
ATAXIA/ COGNITION
EXECUTIVE DYSFUNCTION
PSYCHIATRIC SYMPTOMS
HYPOGONADISM
OPHTHALMOPARESIS
DYSTONIA/ SPASTICITY/ CHOREA
MRI: DENTATE HYPERINTENSITY (T2)
CRAB SIGN
POSTERIOR VERMIS ATROPHY
METABOLIC/ INFECTIONS
WHIPPLE'S DISEASE
OCULOMASTICATORY SKELETAL MYORHYTHMIA
DEMENTIA/ SUPRANUCLEAR OPHTHALMOPLEGIA
MENINGITIS/ CONFUSION/ HEADACHES
PSP PHENOTYPE: PARKINSONISM, UPGAZE RESTRICTION
VERTICAL SACCADE SLOWING
CONVERGENT DIVERGENT NYSTAGMUS (1HZ)
MYOCLONUS/ CHOREA/ MYORHYTHMIA (40%)
ATAXIA (10%)
ARTHRALGIA/ DIARRHOEA/ WEIGHT LOSS
LYMPHADENOPATHY
CAN PRESENT WITHOUT GI SYMPTOMS
DIAGNOSIS:
DUODENAL BIOPSY
CSF: PAS MACROPHAGES/ NORMAL CYTOLOGY(90%)
TROPHERYMA WHIPPLEI PCR: CSF/ BIOPSY
MRI:
FOCAL/ MULTIFOCAL WM LESIONS IN MES TEMPORAL LOBE/ THALAMUS/ HYPOTHALAMUS/ MIDBRAIN
PERIVENTRICULAR WMH/ PACHYMENINGITIS (10%)
CEREBRAL ATROPHY
RX:
TMP-SMX, DOXYCYCLINE/ 3RD GEN CEPHALOSPORINS
BRAIN MINERALIZATION
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
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
LIP-SMACKING/ WRITER'S CRAMP
FRONTAL SUBCORTICAL COGNITIVE DYSFUNCTION
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
WOODHOUSE SAKATI SYNDROME (DCAF17)
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/ ARRHYTHMIAS
SCL30A10/ SCL39A14 (MN TRANSPORTER)
HYPERMANGANESEMIA
BEHAVIORAL CHANGES
PARKINSONISM/ DYSTONIA
SPASTIC PARAPARESIS/ FINE TREMOR
COCKWALK:
TOE WALK/ ERECT SPINE/ ELBOW FLEXED
ALSO SEEN IN SCA3/ PKAN
LAB: POLYCYTHEMIA/ CIRRHOSIS (SCL30A10)
MRI: GPI HYPERINTENSITY (T1)
RX: CHELATION WITH EDTA/ D -PENICILLAMINE
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
