Dominant Spinocerebellar Ataxia (SCA): General³⁵

• Częstość występowania: ~1 to 5 per 100,000

• Średni początek objawów: 3 dekada życia

• Typy mutacji:

• CAG - powtórzenia

• Coding: SCA1; SCA2; SCA3; SCA6; SCA7; SCA17; DRPLA

• Non-coding: SCA12

• Other repeats

• CTG: SCA8

• ATTCT: SCA10

• Other mutations

• PRKCG: SCA14

• FGF14: SCA27

Dominant Spinocerebellar Ataxia (SCA): Differential diagnosis

• Dominant SCA syndromes have many overlapping signs: Difficult to distinguish on clinical grounds

• Najczęstsze objawy we wszystkich typach: Gait ataxia; Dysarthria

• Cechy w niektórych ataksjach: zaburzenia gałkoruchowe; objawy pozapiramidowe; nerwy obwodowe ; Napady.

• Features with some predictive value for specific gene defects

• SCA: Clinical syndromes

• SCA1: Hypermetric saccades; Wzmożenie odruchów głębokich; zaburzenia funkcji wykonawczych; Evoked motor potentials with Long conduction times; OPCA

• SCA2: Slow saccadic velocity; Parkinsonism; Myoclonus or action tremor; zanik mostu (OPCA); KUBA

• SCA3/Machado-Joseph: oczopląs wywołany spojrzeniem; Prominent spasticity; Polyneuropathy; BRAZYLIA & PORTUGALIA

• SCA4: Cerebellar syndrome; Sensory neuropathy; Pyramidal signs

• SCA5: czysty zespół móżdżkowy; objawy opuszkowe; wczesny początek; powolny postęp.

• SCA6: Pure cerebellar syndrome; Lack of family history; Late onset > 50

• SCA7: Pigmentary retinopathy; Hearing loss; Onset in 1st decade

• SCA8: Cerebellar syndrome; Late spasticity; Mild sensory neuropathy

• SCA10: Pure cerebellar syndrome ± Seizures, complex partial; Mexico

• SCA11: Pure cerebellar syndrome; Hyperreflexia; Benign course

• SCA12: Tremor (Early arm); Hyperreflexia; Dementia; Cortical & Cerebellar atrophy

• SCA13: Early childhood onset; Mental retardation

• SCA14: Ataxia; Myoclonus (with early onset); Cognitive decline

• SCA15: Pure cerebellar; Slow progression

• SCA16: Drżenie rak i głowy,

• SCA17: Dysfagia; otępienie; Napady nieświadomości; Extrapyramidal signs

• SCA18: Muscle atrophy; Sensory loss

• SCA19: Cognitive impairment, mild; Myoclonus

• SCA20: Palatal tremor; Dysphonia

• SCA21: Extrapyramidal features

• SCA22: Pure cerebellar syndrome; Slow progression; Hyporeflexia

• SCA23: Ataxia; Sensory loss; Pyramidal signs

• SCA25: Sensory neuropathy; Severe cerebellar atrophy

• SCA26: Pure cerebellar syndrome

• SCA27: Tremor; Dyskinesia; Psychiatric episodes

• SCA28: Oftalmoplegia

• DRPLA: Mioklonie & Padaczka (Onset < 20 years); Choreoathetosis, Dementia, Psychosis (Onset > 20 years); OPCA

• NOTE: Friedreich ataxia may present as a late onset, chronic idiopathic ataxia syndrome

• Polyneuropathy in SCA: aksonalna; czuciowa lub czuciowo - motoryczna

• SCA1: 42%; More with more CAG repeats

• SCA2: 80%

• SCA3: 54%; More with fewer CAG repeats

• SCA4: Sensory loss

• SCA7: 0%

• SCA8: Mild sensory neuropathy

• SCA12: Subclinical; 80%

• SCA14: Vibratory loss

• SCA27: Mild axonal sensory neuropathy

• SCA18: Motor-Sensory

• SCA25: Sensory neuropathy

• Tendon reflexes reduced or absent: SCA 2, 4, 19, 21, 22, Older adult onset SCA 2

• Also see

• Ataxia, Rigidity & Peripheral Neuropathy

• Sensory-Motor Neuropathy + Ataxia

• Other typical clinical features¹⁶

SCA SYNDROMES: DIAGNOSTIC TESTING^35
Clinical sign	1° Testing	2° Testing
Cerebellar ataxia, Pure	SCA6, SCA5	SCA11, SCA14, SCA15, SCA16, SCA22
Spasticity	SCA3	SCA1, SCA7
Peripheral neuropathy	SCA3, SCA4, SCA18, SCA25	SCA1
Cortical disorders
Dementia	SCA17, DRPLA	SCA2, SCA13, SCA19, SCA21
Psychosis	DRPLA, SCA17	SCA3, SCA27 (Episodic)
Epilepsy	SCA10, DRPLA	SCA17
Movement disorders
Chorea	DRPLA, SCA17	SCA1 (Late stage)
Myoclonus	DRPLA	SCA2, SCA19
Tremor	SCA2, SCA8, SCA12	SCA16, SCA21, SCA27
Parkinsonism	SCA3, SCA12	SCA2, SCA21
Dystonia	SCA3	SCA17
Ocular disorders
Ophthalmoplegia	SCA3, SCA2, SCA1
Slow saccades	SCA2	SCA1, SCA3, SCA7, SCA17
Pigmentary retinopathy	SCA7

• Age at onset

• Young adult: SCA 1, 2, 3, 21

• Older adult: SCA 6

• Childhood: SCA 2, 7, 13, SCA27, DRPLA, 25

• Anticipation

• Some SCA: 1, 2, 3, 6, 7, 8, 10, 12, 17, 22 & DRPLA

• More prominent in SCA 7 & DRPLA

• Normal lifespan: SCA 6, 11

• Eye

• Slow saccades

• Early/prominent: SCA 2, 7

• Late: SCA 1, 3, 28

• Very rarely: SCA 6

• Downbeat nystagmus: SCA 6; EA 2

• Maculopathy: SCA 7

• Palatal tremor: SCA 20

• UMN signs

• Common: SCA 1, 3, 7, 12

• Some: SCA 6, 8

• Rarely: SCA 2

• Extrapyramidal

• Akinesia/rigidity/dystonia: SCA 3, 21; SCA 12 (Akinesia)

• Wczesna pląsawica - dominująca: DRPLA; Rarely SCA 2

• Dyskinezy: SCA 27

• mioklonie

• często: SCA 2, 14

• rzadko: SCA 1, 3, 6, 7, 19

• Dysfonia: SCA 20

• Drżenie rak i głowy: SCA 12, 16, 19, 27

• korowe

• Opóźnienie rozwoju: SCA 13, 21; 27

• Zaburzenia poznawcze: SCA 1, 2, 3, 12, 13, 19, 21

• padaczka

• W wieku dorosłym: SCA 10

• Początek w dzieciństwie: DRPLA, SCA 7

• Demencja

• powszechna: DRPLA; SCA17

• o wczesnym początku: SCA 2, 7

• najstarsi pacjenci: SCA 12

• Zajęcie mostu: SCA 1, 2, 3

Dominant Spinocerebellar Ataxia (SCA): Symptomatic Classification

• ADCA I

• Cerebellar syndrome + Other CNS (Pyramidal, Extrapyramidal, Ophthalmoplegia, & Dementia)

• SCA1; SCA2; SCA3; SCA4; SCA8; SCA12; SCA17; SCA27; SCA28

• ADCA II

• Cerebellar syndrome + Pigmentary maculopathy

• SCA7

• ADCA III

• "Pure" cerebellar syndrome ± Mild pyramidal signs

• SCA5; SCA6; SCA10; SCA11; SCA14; SCA15; SCA22; SCA26; SCA NLa

• Other

• SCA13

Dominant Spinocerebellar Ataxia (SCA): CAG repeat disorders

• Ataxias: SCA1; SCA2; SCA3; SCA6; SCA7; SCA12; SCA17; DRPLA

• Clinical correlations with CAG repeat expansion size

CAG REPEAT EXPANSION SIZE

Small

Medium

Large

SCA1		Ataxia Reflexes increased	Spasticity
SCA2	Tremor: Postural	Ataxia Reflexes reduced	Ataxia; Chorea; Dementia
SCA3	Neuropathy (Axonal)	Ataxia; Nystagmus
SCA6	Ataxia: Episodic	Ataxia
SCA7	Ataxia	Ataxia Macular degeneration	Visual loss before ataxia

SCA SYNDROMES: DIAGNOSTIC TESTING^35
Clinical sign		1° Testing	2° Testing
Cerebellar ataxia, Pure		SCA6, SCA5	SCA11, SCA14, SCA15, SCA16, SCA22
Spasticity		SCA3	SCA1, SCA7
Peripheral neuropathy		SCA3, SCA4, SCA18, SCA25	SCA1
Cortical disorders
Dementia		SCA17, DRPLA	SCA2, SCA13, SCA19, SCA21
Psychosis		DRPLA, SCA17	SCA3, SCA27 (Episodic)
Epilepsy		SCA10, DRPLA	SCA17
Movement disorders
Chorea		DRPLA, SCA17	SCA1 (Late stage)
Myoclonus		DRPLA	SCA2, SCA19
Tremor		SCA2, SCA8, SCA12	SCA16, SCA21, SCA27
Parkinsonism		SCA3, SCA12	SCA2, SCA21
Dystonia		SCA3	SCA17
Ocular disorders Ocular disorders Ophthalmoplegia SCA3, SCA2, SCA1 Slow saccades SCA2 SCA1, SCA3, SCA7, SCA17 Pigmentary retinopathy SCA7
Ophthalmoplegia	SCA3, SCA2, SCA1
Slow saccades	SCA2		SCA1, SCA3, SCA7, SCA17
Pigmentary retinopathy	SCA7

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