The Demographic, Clinical and Genetic Characteristics of Dystrophinopathy Patients: a Single Tertiary Center Experience
Öz
Purpose: Duchenne muscular dystrophy DMD is a common X-linked muscular dystrophy characterized by weakness starting in the proximal muscles of the lower extremity. Follow-up of predicted complications and corticosteroid therapy are important in terms of improving quality of life, prolonging survival, treatment, and prenatal diagnosis and genetic counseling should be administered to the families. Our aim was to present the clinical, laboratory and genetic spectrum of patients presenting to our center.Patients and Methods: Patients aged 0–18, diagnosed with DMD or Becker muscular dystrophy BMD , confirmed genetically between January 2013 and January 2018 and admitted to the pediatric neurology policlinic, were examined retrospectively. Data were obtained for demographic characteristics, laboratory findings, neurological examinations, and other investigations genetic evaluation, and organ dysfunction , and multidisciplinary approaches to pathologies expected to accompany the disease.Results: The data for 24 patients who met the inclusion criteria were recorded. The mean age of the patients was 89 ±59.75 months. The mean age at onset of symptoms was 34.50 ±16.1 months , and the mean age at diagnosis was 43.08 ±29.83 months. The main symptoms were delay in starting walking, toe-walking, pseudohypertrophy, fatigue, and weakness climbing stairs. Five patients 20.8% exhibited asymptomatic creatine kinase elevation on laboratory examination due to upper respiratory tract infection. Electromyography was performed on 7 patients, only 3 of whom were compatible with myopathy, the remainder were evaluated as normal. The most frequent deletion sites were exons 46, 47 and 51. Although the patients’ age groups had limited homogeneity, patients with deletions in exons 46, and 47 had lower gross motor function scores.Conclusion: A multidisciplinary approach is very important in terms of quality of life. In particular, the effective screening of mutations is important in terms of offering the patient new therapeutic options
Anahtar Kelimeler
Kaynakça
- Eagle M, Baudouvin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home ventilation. Neuromuscl Disord 2002;12:926–9. [CrossRef]
- Centers for Disease Control and Prevention (CDC). Prevalence of Duchenne/Becker muscular dystrophy among males aged 5–24 years - four states. MMWR Morb Mortal Wkly Rep 2009;16;58:1119– 22. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5840a1. htm
- Bellayou H, Hamzi K, Rafai MA, Karkouri M, Slassi I, Azeddoug H, Nadifi S. Duchenne and Becker muscular dystrophy: contribution of a molecular and immunohistochemical analysis in diagnosis in Morocco. J Biomed Biotechnol 2009:325210. [CrossRef]
- Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989;45:498–506. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1683519/
- Ryder S, Leadley RM, Armstrong N, Westwood M, S de Kock, Butt T, et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 2017;12:79. [CrossRef]
- Nigro G, Comili Politono L, Bain RJ. The incidence and evaluation of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol 1990;26:271–7. [CrossRef]
- Hayes J, Veyckemans F, Bissonnette B. Duchenne muscular dystrophy: an old anesthesia problem revisited. Paediatr Anaesth 2008;18:100–106. [CrossRef]
- Rohde D, Schmitt HJ, Winterpacht A, Münster T. Duchenne muscular dystrophy and malignant hyperthermia: a genetic study of the ryanodine receptor in 47 patients. Eur J Anaesthesiol 2014;31:341–2. [CrossRef]
- Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, et al. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat 2015;36:395–402. [CrossRef]
- Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010;9:177– 89. [CrossRef]
- Koeks Z, Bladen CL, Salgado D, van Zwet E, Pogoryelova O, McMacken G, et al. Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database. J Neuromuscul Dis 2017;4:293–306. [CrossRef]
- Birnkrant DJ, Bushby KM, Amin RS, Bach JR, Benditt JO, Eagle M, et al. The respiratory management of patients with duchenne muscular dystrophy: a DMD care considerations working group specialty article. Pediatr Pulmonol 2010;45:739–48. [CrossRef]
- Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010;9:77–93. [CrossRef]
- Wahbi K. Cardiac involvement in dystrophinopathies. Arch Pediatr 2015;22:37–41. [CrossRef]
- Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health 2015;51:759–64. [CrossRef]
- Hoogerwaard EM, van der Wouw PA, Wilde AA, Bakker E, Ippel PF, Oosterwijk JC, et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 1999;9:347– 51. [CrossRef]
Distrofinopati Hastalarının Demografik, Klinik ve Genetik Özellikleri: Tek Merkez Üçüncü Basamak Deneyimi
Öz
Amaç: Duchenne musküler distrofisi DMD , X’e bağlı olarak kalıtılan bir musküler distrofidir. Alt ekstremite proksimal kaslarında başlayan güçsüzlük ile karekterizedir. Hayat kalitesinin yükseltilmesi ve sağ kalımın uzatılması açısından, öngörülen komplikasyonların tedavisi ve steroid tedavisi önemli olup, ailelere genetik danışmanlık verilmelidir. Bu çalışmadaki amacımız merkezimize başvuran hastalardaki klinik, labaratuvar, genetik spektrumu ortaya koymaktır.Hastalar ve Yöntem: Çalışmada, Ocak 2013-Ocak 2018 arasında çocuk nörolojisi polikliniğimize başvuran 0–18 yaş arasındaki DMD veya Becker musküler distrofi BMD tanısı almış, tanısı genetik olarak doğrulanmış ve verileri yeterli olan olgular retrospektif olarak incelendi. Hastaların, demografik, labaratuvar, nörolojik muayene ve diğer tetkikler genetik, organ disfonksiyonlarına yönelik değerlendirme ve eşlik etmesi öngörülen patolojilerin multidisipliner yaklaşımına yönelik bilgilere ait veriler elde edildi.Bulgular: Çalışmaya alınma kriterlerine uygun 24 hastanın verileri kaydedildi. Hastaların ortalama yaşı 89 ±59,75 ay idi. Hastaların şikayetlerinin başlama yaşı 34,50 ay ±14,77 ve teşhis konulma yaşı 43,08 ay ±29,83 idi. Başlıca yakınma bulguları arasında, geç yürüme, parmak ucu yürüme, baldırlarda sertleşme, çabuk yorulma, merdiven çıkmada güçsüzlük gelmekte idi. Beş hastanın %20,8 ise asemptomatik kreatin kinaz yükseklikleri dış merkezde üst solunum yolu enfeksiyonu tetkik edilir iken bakılan rastlantısal kreatin kinaz yükseklikleri şeklinde idi. Hastaların 7’sine elektromyografi çekilmiş, bunlardan yalnızca 3 tanesinin sonucu miyopati ile uyumlu olarak gelmiş, geri kalanları ise normal olarak değerlendirilmiştir. Tespit edilen, en sık delesyonların 46, 47 ve 51. ekzonlarda olduğu saptanmıştır. Hastaların yaş gruplarının homojen olmaması kısıtlılık oluştursa da 46,47. ekzonlarda delesyonu olanların daha düşük fonksiyonel kaba motor puanına sahip olduğu sonucuna ulaşılmıştır.Sonuç: Multidisipliner yaklaşım hayat kalitesi bakımından çok önemlidir. Özellikle mutasyonların etkin bir şekilde taranması yeni tedavi seçeneklerinin hastaya sunulması bakımından önemlidir
Anahtar Kelimeler
Kaynakça
- Eagle M, Baudouvin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home ventilation. Neuromuscl Disord 2002;12:926–9. [CrossRef]
- Centers for Disease Control and Prevention (CDC). Prevalence of Duchenne/Becker muscular dystrophy among males aged 5–24 years - four states. MMWR Morb Mortal Wkly Rep 2009;16;58:1119– 22. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5840a1. htm
- Bellayou H, Hamzi K, Rafai MA, Karkouri M, Slassi I, Azeddoug H, Nadifi S. Duchenne and Becker muscular dystrophy: contribution of a molecular and immunohistochemical analysis in diagnosis in Morocco. J Biomed Biotechnol 2009:325210. [CrossRef]
- Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989;45:498–506. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1683519/
- Ryder S, Leadley RM, Armstrong N, Westwood M, S de Kock, Butt T, et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 2017;12:79. [CrossRef]
- Nigro G, Comili Politono L, Bain RJ. The incidence and evaluation of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol 1990;26:271–7. [CrossRef]
- Hayes J, Veyckemans F, Bissonnette B. Duchenne muscular dystrophy: an old anesthesia problem revisited. Paediatr Anaesth 2008;18:100–106. [CrossRef]
- Rohde D, Schmitt HJ, Winterpacht A, Münster T. Duchenne muscular dystrophy and malignant hyperthermia: a genetic study of the ryanodine receptor in 47 patients. Eur J Anaesthesiol 2014;31:341–2. [CrossRef]
- Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, et al. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat 2015;36:395–402. [CrossRef]
- Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010;9:177– 89. [CrossRef]
- Koeks Z, Bladen CL, Salgado D, van Zwet E, Pogoryelova O, McMacken G, et al. Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database. J Neuromuscul Dis 2017;4:293–306. [CrossRef]
- Birnkrant DJ, Bushby KM, Amin RS, Bach JR, Benditt JO, Eagle M, et al. The respiratory management of patients with duchenne muscular dystrophy: a DMD care considerations working group specialty article. Pediatr Pulmonol 2010;45:739–48. [CrossRef]
- Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010;9:77–93. [CrossRef]
- Wahbi K. Cardiac involvement in dystrophinopathies. Arch Pediatr 2015;22:37–41. [CrossRef]
- Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health 2015;51:759–64. [CrossRef]
- Hoogerwaard EM, van der Wouw PA, Wilde AA, Bakker E, Ippel PF, Oosterwijk JC, et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 1999;9:347– 51. [CrossRef]
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Research Article |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Haziran 2020 |
| Yayımlandığı Sayı | Yıl 2020Sayı: 2 |