SCA20 is an autosomal dominant adult-onset disorder characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia (summary by Knight et al., 2004).
For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 ... SCA20 is an autosomal dominant adult-onset disorder characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia (summary by Knight et al., 2004). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Knight et al. (2004) reported a family of Anglo-Celtic origin with a relatively pure form of autosomal dominant spinocerebellar ataxia. Fourteen affected members were examined. The age at onset ranged from 19 to 64 years (mean and median ... Knight et al. (2004) reported a family of Anglo-Celtic origin with a relatively pure form of autosomal dominant spinocerebellar ataxia. Fourteen affected members were examined. The age at onset ranged from 19 to 64 years (mean and median both 46.5 years), with an average 10-year earlier onset in the children of affected parents. The most common presenting symptom was dysarthria (in 9 of 14 patients) due to spasmodic dysphonia, which was not associated with laryngeal muscle paralysis. Dysarthria and dysphonia were followed by gait ataxia in 7 patients and upper limb ataxia in 2. There was slow disease progression, with only 1 affected member becoming wheelchair-dependent after 40 years of symptoms. Other variable features included mild pyramidal signs, hypermetric saccades, and mild nystagmus. Palatal tremor or myoclonus was apparent in 10 patients. CT scan showed pronounced dentate calcification in 9 of 9 patients who were imaged. Direct testing for CAG and ATTCT repeat expansions was negative. Coutinho et al. (2006) reported 6 Portuguese families in which a total of 19 individuals were affected with autosomal dominant spinocerebellar ataxia and spasmodic coughing episodes. Paroxysmal coughing attacks first occurred at 25 to 55 years of age, whereas signs of cerebellar ataxia developed later at 40 to 65 years of age. In most patients, the coughing came in bursts without clear precipitating factors, occurred daily, and lasted several minutes. The coughing episodes tended to decrease in frequency and severity with age and after the onset of cerebellar ataxia. There was no evidence of respiratory diseases, allergies, or gastric complaints. Ten patients with long-standing disease had downbeat nystagmus, and 1 patient had dentate calcifications. Coutinho et al. (2006) suggested that the disorder in these families may be similar to that reported by Knight et al. (2004) and may result from dysfunction of cerebellar neural networks that influence breathing and coughing reflexes.
Clinical information on spinocerebellar ataxia type 20 (SCA20) derives from studies of the index pedigree, an Australian family of Anglo-Celtic descent [Knight et al 2004]. ...
DiagnosisClinical DiagnosisClinical information on spinocerebellar ataxia type 20 (SCA20) derives from studies of the index pedigree, an Australian family of Anglo-Celtic descent [Knight et al 2004]. The diagnosis should be considered in individuals with a slowly progressive ataxia without sensory features who have the following findings:Onset with dysarthria that may be of abrupt onset, rather than with gait ataxia (seen in ~66%) Palatal tremor (in ~66%) Family history consistent with autosomal dominant inheritance Additional findings may include the following: Hypermetric horizontal saccades (without nystagmus or disturbance of vestibulo-ocular reflex gain) in about half Mild hyperreflexia (typically without spasticity or extensor plantar responses) in a minority Postural tremor of arms with or without involvement of the head (seen in a minority; may be the first symptom) NeuroimagingCT scan (Figure 1) shows pronounced dentate calcification, typically without concomitant pallidal calcification, at an early stage of the illness (≤3 years from onset).MRI (Figure 2) shows mild to moderate pan cerebellar atrophy, with low dentate signal on T1 and T2-weighted sequences (consistent with calcification) and normal cerebrum and brain stem (apart from increased inferior olivary T2 signal in some, as a correlate of palatal tremor). FigureFigure 1 III:12. CT scan showing heavy dentate calcification and pan cerebellar atrophy in a 62-year-old individual with mild ataxia; three years after symptom onset III:16. CT scan slices at two levels of the dentate showing heavy dentate (more...)FigureFigure 2. MRI axial proton density images showing (a) inferior olivary hypertrophy and (b) low dentate signal consistent with dentate calcification in a 54-year-old individual 16 years after onset Note: Roman:arabic numeral combinations refer (more...)Neurophysiology. Nerve conduction studies are normal. TestingIndices of calcium metabolism (serum concentrations of calcium, phosphate, magnesium, alkaline phosphatase, parathyroid hormone, 25-hydroxy vitamin D) are normal.Molecular Genetic TestingLocus. Knight et al [2008] reported a 260-kb duplication of 11q12.2-11q12.3 as the probable cause of SCA20 in the index family. The locus for SCA20 lies within the pericentromeric region of chromosome 11. The gene is unknown. Although the candidate region includes SPTBN2 (the gene in which mutation is responsible for SCA5), SPTBN2 mutations have been excluded as the cause of SCA20 [Lorenzo et al 2006].Table 1. Summary of Molecular Genetic Testing Used in Spinocerebellar Ataxia Type 20View in own windowGene SymbolTest MethodMutations DetectedMutation Detection FrequencyTest AvailabilityUnknownLinkage analysisN/A N/A Research only Direct DNA 1260-kb duplicationUnknownN/A = not applicable1. Direct DNA methods may include mutation analysis, mutation scanning, sequence analysis, or other means of molecular genetic testing.Testing StrategyTo confirm/establish the diagnosis in a proband. Because the gene in which mutations cause SCA20 has not been identified, the diagnosis of SCA20 is based on clinical findings. Genetically Related (Allelic) DisordersNo genetically related disorders are known.
Clinical information on spinocerebellar ataxia type 20 (SCA20) is based on the index pedigree, an Australian family of Anglo-Celtic descent that is the only family with SCA20 reported to date [Knight et al 2004, Storey et al 2005]. ...
Natural HistoryClinical information on spinocerebellar ataxia type 20 (SCA20) is based on the index pedigree, an Australian family of Anglo-Celtic descent that is the only family with SCA20 reported to date [Knight et al 2004, Storey et al 2005]. The 16 affected family members had onset between age 19 and 64 years (mean 47). SCA20 presents with dysarthria without ataxia in a majority (10/16); the dysarthria may be of abrupt (2/16) or subacute (1/16) onset. It often combines the clinical appearance of spasmodic adductor dysphonia with cerebellar dysarthria. Other initial symptoms were dysarthria with simultaneous gait ataxia (2/16), gait ataxia alone (2/16), upper limb kinetic and isometric tremor (1/16), and episodic vertigo (1/16).Progression of SCA20, as judged by cross-sectional data, appears to be relatively slow; all affected members of this family were able to walk with or without gait aids except one, who became wheelchair dependent after 40 years of symptoms. Another required a feeding gastrostomy after 15 years of symptoms. The clinical picture usually (10/16) includes palatal tremor ("myoclonus") without ear click, although this finding can be subtle. Gaze-evoked nystagmus is unusual (3/16). In two it was impersistent; in another affected individual persistent down-beating nystagmus was evident. Saccades are typically hypermetric into down gaze (10/16) and horizontally (8/16). The vestibulo-ocular reflex gain, as judged by dynamic vs static visual acuity, is normal, correlating with absence of movement-induced oscillopsia. Minor pyramidal signs (brisk knee jerks, crossed adductor spread) are seen in a minority (5/16), but none have spastic tone or extensor plantar responses. Postural and kinetic tremor of the upper limbs, the presenting feature in one individual, was evident in only one other family member. Only one displayed intention tremor (as distinct from dysmetria and dyssynergia) on the finger/nose test.Other extrapyramidal features (apart from slowing of repetitive movements without movement decay) are absent. None had a history of cognitive decline.
The differential diagnosis of spinocerebellar ataxia type 20 (SCA20) is essentially that of its component features, as the constellation of progressive, dominantly inherited ataxia, early dentate calcification, and (often) palatal tremor is distinctive....
Differential DiagnosisThe differential diagnosis of spinocerebellar ataxia type 20 (SCA20) is essentially that of its component features, as the constellation of progressive, dominantly inherited ataxia, early dentate calcification, and (often) palatal tremor is distinctive.Inherited ataxia. See Ataxia Overview. Dentate calcification appears early in SCA20; it was seen in five affected individuals who had been symptomatic for five years or less. While dentate calcification is common in the general population with increasing age, affecting 0.7% of those older than age 65 years in one study [Harrington et al 1981], it rarely occurs in the absence of basal ganglia calcification (as it did in 9/11 individuals in the family with SCA20). Hyperparathyroidism and pseudohypoparathyroidism with basal ganglia (and dentate) calcification may be dominantly inherited, and can be excluded on biochemical testing. Dentatorubral-pallidoluysian atrophy can include pallidal microcalcification in the Haw River phenotype. Dominant "familial idiopathic brain calcification" (OMIM 213600) (see Familial Idiopathic Basal Ganglia Calcification) has been reported in several families, but basal ganglia calcification dominates, and the clinical presentation includes cognitive decline and parkinsonism rather than ataxia. Palatal tremor ("myoclonus") may be seen in the following situations, while dentate calcification is not: In conjunction with progressive ataxia in sporadic (i.e., not inherited) cases, possibly representing a unique degenerative syndrome [Sperling & Herrmann 1985] Rarely, in multiple system atrophy-cerebellar type (MSAC) In early adult-onset Alexander disease, in which bulbar palsy and spastic tetraparesis are also seen. Inheritance is autosomal dominant. In a dominant branchial myoclonus syndrome with ataxia [de Yebenes et al 1988], which may be a phenotypic variant of adult-onset Alexander disease Dysphonia (which is apparent in SCA20 rather than confirmed on formal voice analysis) may also be seen with ataxia and motor neuropathy [Barbieri et al 2001]; this latter syndrome appears to be inherited in an autosomal recessive manner. The presence of motor neuropathy and the absence of dentate calcification and palatal tremor also serve to distinguish this syndrome from SCA20. Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to , an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).
To establish the extent of disease in an individual diagnosed with spinocerebellar ataxia type 20 (SCA20), the following evaluations are recommended:...
ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease in an individual diagnosed with spinocerebellar ataxia type 20 (SCA20), the following evaluations are recommended:Careful clinical and neurologic evaluation Speech assessment Treatment of ManifestationsAffected persons should be followed by a neurologist with consultation from physiatrists and physical and occupational therapists.Although neither exercise nor physical therapy has been shown to stem the progression of incoordination or muscle weakness, individuals should maintain activity. Canes and walkers help prevent falls. Modification of the home with such conveniences as grab bars, raised toilet seats, and ramps to accommodate motorized chairs may be necessary. Speech therapy and communication devices such as writing pads and computer-based devices may benefit those with dysarthria or dysphonia. Weighted eating utensils and dressing hooks help maintain a sense of independence. Weight control is important because obesity can exacerbate difficulties with ambulation and mobility. When dysphagia becomes troublesome, videofluoroscopic swallow evaluation can identify the consistency of food least likely to trigger aspiration.Prevention of Secondary ComplicationsSecondary complications are unlikely in the early years of the disease. Later, prevention of falls via appropriate gait aids and home modifications, and (if falls are frequent) a personal alarm system may be required. To limit the likelihood of fractures resulting from falls, bone density should be estimated and osteoporosis treated if present.Vitamin supplements are recommended, particularly if caloric intake is reduced. Weight control is important because obesity can exacerbate difficulties with ambulation and mobility. SurveillanceThe following are appropriate:Periodic speech assessment if dysphagia becomes a problem Routine follow up with a neurologist about every two years or as needed Agents/Circumstances to AvoidAffected individuals should avoid alcohol as well as medications known to cause nerve damage (e.g., isoniazid).Therapies Under InvestigationSearch ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.OtherTremor-controlling drugs do not work well for cerebellar tremors. Education for affected individuals and their families is the cornerstone of management.
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....
Molecular GeneticsInformation in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.Table A. Spinocerebellar Ataxia Type 20: Genes and DatabasesView in own windowLocus NameGene SymbolChromosomal LocusProtein NameSCA20Unknown11p13-q11UnknownData are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.Table B. OMIM Entries for Spinocerebellar Ataxia Type 20 (View All in OMIM) View in own window 608687SPINOCEREBELLAR ATAXIA 20; SCA20Normal allelic variants. None identifiedPathologic allelic variants. The 260-kb duplicated segment reported by Knight et al [2008] includes ten known and two unknown genes. It was not found in 1,129 control samples, suggesting that it is not merely a copy number variant. Normal gene product. One of the known genes in the duplicated region, DAGLA, is potentially an attractive candidate as it is highly expressed in murine Purkinje cells. Abnormal gene product. It is presumed that, if the duplication is indeed causative, the mechanism would be a gene dosage effect, with 150% of the normal level of product from a gene or genes within the duplicated segment resulting in cerebellar dysfunction. Other examples of a pathogenic effect from increased gene dosage include Parkinson disease from α-synuclein duplications and Alzheimer disease from trisomy 21 (and therefore effective “duplication” of APP).