CLINICAL CHARACTERISTICS: Spinocerebellar ataxia type 38 (SCA38) is characterized as a pure cerebellar ataxia with symptoms typically manifesting in the fourth decade of life. The most common presenting features are nystagmus and slowly progressive gait ataxia. As the disease progresses, cerebellar symptoms (limb ataxia, dysarthria, dysphagia, diplopia on the horizontal line) may emerge, and affected individuals may experience sensory loss. In the later stages of the condition, ophthalmoparesis followed by ophthalmoplegia may occur. Features that distinguish SCA38 from other spinocerebellar ataxias include pes cavus without paresis, hyposmia, hearing loss, and anxiety disorder. Dementia and extrapyramidal signs are not common features of SCA38. Brain imaging typically demonstrates cerebellar atrophy mainly affecting the vermis without atrophy of the cerebral cortex and a normal appearance of the brain stem. With disease progression, nerve conduction velocities and electromyography demonstrate a sensory and motor axonal polyneuropathy in all four extremities. Life span is apparently not decreased. DIAGNOSIS/TESTING: The diagnosis of SCA38 is established in a proband with progressive gait ataxia and a heterozygous pathogenic variant in ELOVL5 identified by molecular genetic testing. MANAGEMENT: Treatment of manifestations: Management remains supportive and may include physical therapy to ameliorate coordination difficulties; crutches and walkers; home adaptations to avoid falls or accommodate motorized chairs; speech/language therapy; weighted utensils; hearing aids for those with hearing loss; and standard therapy for anxiety. Prevention of secondary complications: Weight control, as obesity can exacerbate difficulties with ambulation and mobility; vitamin supplements for those with reduced caloric intake. Surveillance: Annual examination by a physician who is experienced in movement disorders and ataxia. Agents/circumstances to avoid: Alcohol and medications known to affect cerebellar function. Therapies under investigation: Docosahexaenoic acid (DHA) supplementation (600 mg/day) may improve clinical symptoms and cerebellar hypometabolism; no data on the effectiveness of DHA in postponing signs and symptoms of SCA38 in asymptomatic individuals with a heterozygous pathogenic variant in ELOVL5 have been published. GENETIC COUNSELING: Spinocerebellar ataxia type 38 (SCA38) is inherited in an autosomal dominant manner. All reported individuals diagnosed with SCA38 have an affected parent. The offspring of an affected individual are at 50% risk of inheriting the ELOVL5 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known; however, requests for prenatal diagnosis of adult-onset diseases are uncommon and require careful genetic counseling.

Spinocerebellar Ataxia Type 38.

Alfredo Brusco;Eleonora Di Gregorio;
2019

Abstract

CLINICAL CHARACTERISTICS: Spinocerebellar ataxia type 38 (SCA38) is characterized as a pure cerebellar ataxia with symptoms typically manifesting in the fourth decade of life. The most common presenting features are nystagmus and slowly progressive gait ataxia. As the disease progresses, cerebellar symptoms (limb ataxia, dysarthria, dysphagia, diplopia on the horizontal line) may emerge, and affected individuals may experience sensory loss. In the later stages of the condition, ophthalmoparesis followed by ophthalmoplegia may occur. Features that distinguish SCA38 from other spinocerebellar ataxias include pes cavus without paresis, hyposmia, hearing loss, and anxiety disorder. Dementia and extrapyramidal signs are not common features of SCA38. Brain imaging typically demonstrates cerebellar atrophy mainly affecting the vermis without atrophy of the cerebral cortex and a normal appearance of the brain stem. With disease progression, nerve conduction velocities and electromyography demonstrate a sensory and motor axonal polyneuropathy in all four extremities. Life span is apparently not decreased. DIAGNOSIS/TESTING: The diagnosis of SCA38 is established in a proband with progressive gait ataxia and a heterozygous pathogenic variant in ELOVL5 identified by molecular genetic testing. MANAGEMENT: Treatment of manifestations: Management remains supportive and may include physical therapy to ameliorate coordination difficulties; crutches and walkers; home adaptations to avoid falls or accommodate motorized chairs; speech/language therapy; weighted utensils; hearing aids for those with hearing loss; and standard therapy for anxiety. Prevention of secondary complications: Weight control, as obesity can exacerbate difficulties with ambulation and mobility; vitamin supplements for those with reduced caloric intake. Surveillance: Annual examination by a physician who is experienced in movement disorders and ataxia. Agents/circumstances to avoid: Alcohol and medications known to affect cerebellar function. Therapies under investigation: Docosahexaenoic acid (DHA) supplementation (600 mg/day) may improve clinical symptoms and cerebellar hypometabolism; no data on the effectiveness of DHA in postponing signs and symptoms of SCA38 in asymptomatic individuals with a heterozygous pathogenic variant in ELOVL5 have been published. GENETIC COUNSELING: Spinocerebellar ataxia type 38 (SCA38) is inherited in an autosomal dominant manner. All reported individuals diagnosed with SCA38 have an affected parent. The offspring of an affected individual are at 50% risk of inheriting the ELOVL5 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known; however, requests for prenatal diagnosis of adult-onset diseases are uncommon and require careful genetic counseling.
GeneReviews
Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A
1
12
https://www.ncbi.nlm.nih.gov/books/
Ataxia, ELOVL5
Alfredo Brusco, Eleonora Di Gregorio, Barbara Borroni
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1706457
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