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Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020)
Background Muscular dystrophies (MD) and myopathies are a distinct group of clinically and genetically heterogeneous inherited muscle diseases. They cause muscle weakness often with cardiac, pulmonary, and musculoskeletal dysfunction, leading to reduced longevity. MDs and myopathies present across a...
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| Language: | English |
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Department of Paediatrics and Child Health
2022
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| _version_ | 1867613314401435648 |
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| access_status_str | Open Access |
| author | Oshi, Mohammed Mohammed Ahmed |
| author2 | Wilmhurst, Jo |
| author_browse | Oshi, Mohammed Mohammed Ahmed Wilmhurst, Jo |
| author_facet | Wilmhurst, Jo Oshi, Mohammed Mohammed Ahmed |
| author_sort | Oshi, Mohammed Mohammed Ahmed |
| collection | Thesis |
| description | Background Muscular dystrophies (MD) and myopathies are a distinct group of clinically and genetically heterogeneous inherited muscle diseases. They cause muscle weakness often with cardiac, pulmonary, and musculoskeletal dysfunction, leading to reduced longevity. MDs and myopathies present across all life stages. Delineation of this condition and specifically the subgroups with additional connective tissue involvement is poorly described in subSaharan African populations. Aim To delineate the phenotypic, and where possible genotypic expression, of muscular dystrophies and myopathies with connective tissue involvement in an African setting. Methods A retrospective cohort study was undertaken of children with muscular dystrophy / myopathy and connective tissue involvement who attend a dedicated neuromuscular service. Patient demographics, diagnosis and clinical profile was collated. Patients were allocated into two groups, congenial /infantile and childhood, based on age of onset. Muscle biopsy characteristics, biochemical findings, and where available, genetic analysis were captured. Based on the combined findings children were categorised into connective tissue variant groups i.e., Collagen 6 related myopathies, Rigid Spine Syndrome (SELENON phenotype), LMNA-related, ACTA1 related myopathies, MDC1A, and a subgroup who could not be categorised. Descriptive statistics and categorical variables were compared to evaluate primary study questions. Ethical approval was obtained by the University of Cape Town Human Research Ethics Committee (HREC:549/2019). Families gave informed consent prior to enrolment. Results A total of 57 children were reviewed, 50 of whom met the inclusion criteria of connective tissue spectrum in the setting of muscle disease (female to male ratio 1.3:1). There was a predominance in children from African ancestries, followed by those of European descent. 31/50 (62%) presented in the congenital-infantile age period, the remainder presented after 2 years of age. Children with congenital/infantile onset were more likely to lose independent ambulation compared to children with childhood onset (5/8, 62% vs 3/8 38%). Scoliosis complicated the course in 29/50 (58%) children, again affecting congenital/infantile onset children more when compared to the childhood onset group (19/29, 65%, vs 10/29,35%); (p=0.003), and spinal rigidity was more prevalent in the congenital/infantile onset compared to the childhood group, (8/11 (73%) vs 3/11 (27%)). The childhood group were statistically more at risk of suffering compromising respiratory muscle dysfunction (32/45, 71%, vs 13/45,29%) ;(p=0.04 ). Genetic diagnosis was available for 9 patients. Based on this and the combined phenotypes n=17 were considered part of the Collagen 6 group, n=7 Rigid Spine Syndrome and n=14 LMNA spectrum, n=3 under the ACTA1 mutation expression, n=2 LAMA2 and the remaining 7 could not be categorized or did not fall under one of the main groupings. Conclusion This study confirmed expression of this subgroup of muscular diseases with connective tissue involvement within the SSA population. The burden of disease from these conditions is across multiple systems and significant, requiring specialized care. Early recognition and referral to neuromuscular centre, would improve the potential outcomes for these children with collaborative multidisciplinary team. Serum creatine kinase (CK) levels and clinical markers such as rigid spine, dropped head, and skin laxity could be used in resource limited settings for probable and possible phenotype. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/36097 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:34:10.861Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Department of Paediatrics and Child Health |
| publisherStr | Department of Paediatrics and Child Health |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/36097 Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) Oshi, Mohammed Mohammed Ahmed Wilmhurst, Jo Paediatrics Neurology Background Muscular dystrophies (MD) and myopathies are a distinct group of clinically and genetically heterogeneous inherited muscle diseases. They cause muscle weakness often with cardiac, pulmonary, and musculoskeletal dysfunction, leading to reduced longevity. MDs and myopathies present across all life stages. Delineation of this condition and specifically the subgroups with additional connective tissue involvement is poorly described in subSaharan African populations. Aim To delineate the phenotypic, and where possible genotypic expression, of muscular dystrophies and myopathies with connective tissue involvement in an African setting. Methods A retrospective cohort study was undertaken of children with muscular dystrophy / myopathy and connective tissue involvement who attend a dedicated neuromuscular service. Patient demographics, diagnosis and clinical profile was collated. Patients were allocated into two groups, congenial /infantile and childhood, based on age of onset. Muscle biopsy characteristics, biochemical findings, and where available, genetic analysis were captured. Based on the combined findings children were categorised into connective tissue variant groups i.e., Collagen 6 related myopathies, Rigid Spine Syndrome (SELENON phenotype), LMNA-related, ACTA1 related myopathies, MDC1A, and a subgroup who could not be categorised. Descriptive statistics and categorical variables were compared to evaluate primary study questions. Ethical approval was obtained by the University of Cape Town Human Research Ethics Committee (HREC:549/2019). Families gave informed consent prior to enrolment. Results A total of 57 children were reviewed, 50 of whom met the inclusion criteria of connective tissue spectrum in the setting of muscle disease (female to male ratio 1.3:1). There was a predominance in children from African ancestries, followed by those of European descent. 31/50 (62%) presented in the congenital-infantile age period, the remainder presented after 2 years of age. Children with congenital/infantile onset were more likely to lose independent ambulation compared to children with childhood onset (5/8, 62% vs 3/8 38%). Scoliosis complicated the course in 29/50 (58%) children, again affecting congenital/infantile onset children more when compared to the childhood onset group (19/29, 65%, vs 10/29,35%); (p=0.003), and spinal rigidity was more prevalent in the congenital/infantile onset compared to the childhood group, (8/11 (73%) vs 3/11 (27%)). The childhood group were statistically more at risk of suffering compromising respiratory muscle dysfunction (32/45, 71%, vs 13/45,29%) ;(p=0.04 ). Genetic diagnosis was available for 9 patients. Based on this and the combined phenotypes n=17 were considered part of the Collagen 6 group, n=7 Rigid Spine Syndrome and n=14 LMNA spectrum, n=3 under the ACTA1 mutation expression, n=2 LAMA2 and the remaining 7 could not be categorized or did not fall under one of the main groupings. Conclusion This study confirmed expression of this subgroup of muscular diseases with connective tissue involvement within the SSA population. The burden of disease from these conditions is across multiple systems and significant, requiring specialized care. Early recognition and referral to neuromuscular centre, would improve the potential outcomes for these children with collaborative multidisciplinary team. Serum creatine kinase (CK) levels and clinical markers such as rigid spine, dropped head, and skin laxity could be used in resource limited settings for probable and possible phenotype. 2022-03-15T12:11:00Z 2022-03-15T12:11:00Z 2021 2022-03-14T11:08:58Z Master Thesis Masters MPhil http://hdl.handle.net/11427/36097 eng application/pdf Department of Paediatrics and Child Health Faculty of Health Sciences |
| spellingShingle | Paediatrics Neurology Oshi, Mohammed Mohammed Ahmed Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| thesis_degree_str | Master's |
| title | Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| title_full | Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| title_fullStr | Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| title_full_unstemmed | Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| title_short | Delineation of the genotype and phenotype of children presenting with dystrophies, excluding dystrophinophathies, in the Western Cape of South Africa. (2019-2020) |
| title_sort | delineation of the genotype and phenotype of children presenting with dystrophies excluding dystrophinophathies in the western cape of south africa 2019 2020 |
| topic | Paediatrics Neurology |
| url | http://hdl.handle.net/11427/36097 |
| work_keys_str_mv | AT oshimohammedmohammedahmed delineationofthegenotypeandphenotypeofchildrenpresentingwithdystrophiesexcludingdystrophinophathiesinthewesterncapeofsouthafrica20192020 |