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Spinocereballar Ataxia +

Spinocereballar Ataxia +. Excerpts from Dr Hedera’s Ataxia Lecture (I took pictures of his slides during lecture and transcribed) Winter 2014. SCA 1. Caused by CAG expansion in the ATXN1/ataxin-1 gene Typical age of onset is in the 4 th decade

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Spinocereballar Ataxia +

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  1. Spinocereballar Ataxia + Excerpts from DrHedera’s Ataxia Lecture (I took pictures of his slides during lecture and transcribed) Winter 2014

  2. SCA 1 • Caused by CAG expansion in the ATXN1/ataxin-1 gene • Typical age of onset is in the 4th decade • Typical clinical features: bulbar signs, corticospinal signs, parkinsonism • AD, gene on 6p23 • 6% of all AD cerebellar ataxias

  3. SCA 2 • Caused by CAG expansion in the ATXN2/ataxin-2 gene • Typical age of onset is in the 4th decade • Typical clinical features: slow horizontal saccades, neuropathy, dementia • Some patients may have PD-like disease (almost impossible to differentiate from PD) • AD, gene on 12q24 • 13% of all AD cerebellar ataxias

  4. SCA 3 • Aka Machado-Joseph disease • Caused by CAG expansion in the ATXN3/ataxin-3 gene (MJD protein 1) • Typical age of onset is in the 4th decade • Great imitator • Several subtypes known: spastic ataxia, parkinsonism, hereditary spastic paraplegia, peripheral neuropathy • AD, gene on 14q24.3-q31 • 23% of all AD cerebellar ataxia

  5. SCA 6 • Caused by CAG expansion in the CACNA1A/voltage-dependent P/Q-type calcium channel alpha-1 subunit • Point mutation in the same gene can cause episodic ataxia EA2 • Typical onset is in the 6th decade • The vast majority have pure cerebellar ataxia • Parkinsonism is relatively rare • AD, gene on 19p13

  6. SCA 7 • Caused by CAG expansion in the ATXN7/ataxin-7 gene • Typical age of onset is in the 4th decade • Retinal degeneration is the hallmark • AD, gene on 3p21.1-p12

  7. SCA 10 • Caused by the abnormal ATTCT pentanucleotide repeat expansion in ATXN10 gene • Characterized by slowly progressive cerebellar ataxia • Typical age of onset is in the 4th decade • Exclusively found in Latin American populations, particularly those with Amerindian admixture • Epilepsy and dementia are common

  8. SCA 14 • Caused by mutations in the PRKCG/protein kinase C gamma type gene • Typical features include slowly progressive cerebellar ataxia, axial myoclonus, cognitive impairment, tremor and sensory loss • Parkinsonian features are common • Episodic axial myoclonus manifest as irregular tremulous movements of the trunk and head lasting minutes to hours is common

  9. SCA 17 • Caused by CAG/CAA repeat expansion in the TBP gene • Characterized by ataxia, dementia and involuntary movements, including chorea and dystonia • Psychiatric symptoms, pyramidal signs and rigidity are common • Typical age of onset is in the 5th decade

  10. DRPLA • Dentatorubralpallidoluysian atrophy is another type of CAG expansion disorder in the ATN1 gene • The age of onset is from 1 to 62 years with a mean age of onset of 30 years. The clinical presentation varies depending on the age of onset. • The cardinal features in adults are ataxia, choreoathetosis, psychiatric disturbances and dementia • Cardinal features in children are progressive intellectual deterioration, behavioral changes, myoclonus and epilepsy • DRPLA in a large AA family in North Carolina was referred to as Haw River syndrome

  11. Spastic ataxia • Several types of SCA have signs of pyramidal tract lesion (SCA 1, 2, 3, 7), but ataxia is dominant and this usually does not represent a diagnostic dilemma • Few patients with MJD/SCA3 with “pure” spastic paraparesis have been reported • Clinical analysis of these patients demonstrated prominent extraocular movement abnormalities that are absent in HSP, PLS and ALS

  12. Friedreich ataxia • Most common type of ataxia (2-4/100,000) • Typical clinical picture consists of ataxia, areflexia with upgoing toes, neuropathy with distal weakness (and hammartoes) • Also has systemic manifestations (cardiomyopathy, diabetes, scoliosis) • Recently patients with typical mutation (homozygous GAA expansion in the first intron) presenting with “pure” spastic paraplegia have been reported • Distal weakness and signs of sensor neuropathy may suggest this dx, but are non-specific • Consider genetic testing in patients with apparently sporadic ataxia or spastic paraparesis or with possibility of autosomal recessive inheritence because of the need for cardiac and endocrine care

  13. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) • FMR1 related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and FMR1-related primary ovarian insufficiency (POI) • FXTAS occurs in males (and some females) who have a FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor • All individuals with FXTAS have MR1 premutationtrinucleotide repeats ranging from 55 to ~200 • A definite dx of FXTAS requires the presence of a premutation in FMR1 and white lesions on MRI in the middle cerebellar peduncle and/or brainstem (the major neuroradiologic sign) with either intention tremor or gait ataxia (the two major clinical signs) • Other minor neuroradiologic criteria include MRI white matter lesions in the cerebral white matter or moderate to generalized atrophy • Other minor clinical criteria include parkinsonism, moderate to severe working memory deficits, or executive cognitive function deficits

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