Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families

Abstract

BackgroundTo date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin.ObjectiveTo present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families.MethodsThe study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating Scale derived from the modified international ataxia rating scale. Molecular genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was performed at the National Health Laboratory Service at Groote Schuur Hospital and the Division of Human Genetics, University of Cape Town, SA. The clinical and radiological features were evaluated in seven families with autosomal dominant cerebellar ataxia. Molecular genetic analysis was completed on individuals representing three of the seven families.ResultsAll affected families were ethnic Zambians from various tribes, originating from three different regions of the country (Eastern, Western and Central province). Thirty-four individuals from four families had phenotypic features of SCA7. SCA7 was confirmed by molecular testing in 10 individuals from 3 of these families. The age of onset of the disease varied from 12 to 59 years. The most prominent phenotypic features in these families were gait and limb ataxia, dysarthria, visual loss, ptosis, ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected members of the SCA7 families had progressive macular degeneration and cerebellar atrophy. All families displayed marked anticipation of age at onset and rate of symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56 repeats. Three additional families were found to have clinical phenotypes associated with autosomal dominant SCA, however, DNA was not available for molecular confirmation. The age of onset of the disease in these families varied from 19 to 53 years. The most common clinical picture in these families included a combination of cerebellar symptoms with slow saccadic eye movements, peripheral neuropathy, dementia and tremor.ConclusionSCA is prevalent in ethnic Zambian families. The SCA7 families in this report had similar clinical presentations to families described in other African countries. In all families, the disease had an autosomal dominant pattern of inheritance across multiple generations. All families disp...

Clinical characterisation and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7

“…Clinically, visual disturbances may precede other symptoms in SCA7, and multimodal imaging may facilitate the observation of retinal change and is bene cial to detect early lesions of ATXN7-related retinopathy. The retinal phenotype in our patients indicating a cone-rod dystrophy generally agrees with previous reports 1,[8][9][10][11] . In our cohort, all the patients complained of progressive bilateral visual loss, and most cases reported visual disturbance earlier than dyskinesia or dysarthria.…”

“…Presenting visual symptoms may include photophobia, dyschromatopsia, decreased vision and hemeralopia 7 . The appearance of the fundus in SCA7 is variable, and the reported phenotypes range from normal appearance, occult macular dystrophy (OMD), macular dystrophy and cone-rod dystrophy 1,[8][9][10][11] . Ocular motor abnormalities may include slowed saccades, saccadic pursuits, saccadic dysmetria and gaze-evoked nystagmus 7 , which are relatively non-speci c for olivopontocerebellar atrophies.…”

“…There have been a number of reports on the visual disturbances in AXTN7-associated retinopathy 1,[8][9][10][11] . However, there is limited data on the ophthalmic clinical spectrum and genetics of SCA7 from the Chinese population.…”

Spinocerebellar ataxia Type 7: clinical and genetic study of a new Moroccan family

“…It is the first Moroccan family with SCA7 in the South of Morocco. There are a few SCA7 reports from Algeria, Angola, Cape Verde, Liberia, Mali, Morocco, South Africa, Tunisia and Zambia [ 6 , 7 ].…”

Nonmotor symptoms in spinocerebellar ataxias (SCAs)

“…Another study of SCA6 patients did not find cognitive abnormalities compared to healthy controls [44]. A series of 19 African patients with SCA7 described dementia in almost half of affected cases, particularly as a late feature [45]. A longitudinal study, however, found only minor cognitive changes in SCA7, comparable to SCA6 [46].…”