Öz
Autism affects approximately 1/100 people. The main problems in this disease, in which genetic factors play important causative roles appear in areas of social interactions, language acquisition and communication skills. Stereotypical movements and serious limitation in interests are seen in the majority of patients. Intellectual deficiency seen in 75% of the patients requires life-long social and educational support, therefore causes a serious health concern. Data obtained from research studies for delineating autism etiology revealed significant correlations between autism and some cytogenetic aberrations in almost every chromosome. Recent technical advances in molecular genetics facilitated evaluations in a finer level and thus caused the identification of significant associations between autism and genomic copy number variations. In addition to some chromosomal abnormalities revealed via conventional cytogenetic analyses and various copy number variations detected through molecular methods, many genetic syndromes caused by single gene mutations have autism signs. Delineation of etiopathogenesis has major implications in the planning of a treatment strategy and genetic counseling related with disease course and recurrence risk. Cytogenetic and molecular tests for autism diagnosis must be performed according to the results of algorithms formed with genetic details and genetic abnormalities and syndromes related with autism must be ruled out in differential diagnosis. Thus, the prevention of potential complications and the onset of appropriate therapy can be possible. Conclusively, medical management of autistic patients must be handled by a team approach and this team must consist of clinicians appropriate for the patient’s age, psychologist/pedagogue, physiotherapist, speech therapist and a medical geneticist.
Anahtar Kelimeler
Kaynakça
- Akçakın M. [Development defining in autism spectrum disorders]. Turkiye Klinikleri J Pediatr Sci 2007;3(3):14-24.
- American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association.
- Atladottir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends in reported diagnoses of childhood neuropsychiatric disorders. Arch Pediatr Adolesc Med 2007;161:193-8.
- Bhandari A, Sandlow JI, Brannigan RE. Androlog summary: Risks to offspring associated with advanced paternal age. J Androl 2011;32(2):121-2.
- Carter AS, Black DO, Tewani S, Connoly CE, Kadlec MB, Tager-Flusberh H. Sex differences in toddlers with autism spectrum disorders. J Autism Dev Disord 2007;37:86-97.
- Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children. JAMA 2001;285:3093-9.
- DiCicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C, et al. The developmental neurobiology of autism spectrum disorder. J Neurosci 2006;26(26):6897-906.
- Erden G, Akçakın M, Gümüş Doğan D, Öztürk Erdem İ. [Pediatricians and autism: Difficulties in Diagnosis]. Turkiye Klinikleri J Pediatr Sci 2010;19(1):9-15.
- Fitzpatrick M. The end of the road for the campaign against MMR. Br J Gen Pract 2007;57(541):679.
- Gillberg C, Gillberg C, Rastam M, ,Wentz E. The Asperger syndrome (and high-functioning autism) diagnostic interview (ASDI): a preliminary study of a new structured clinical interview. Autism 2001;5(1):57-66.
- Gurrieri F. Working up autism: The practical role of medical genetics. Am J Med Genet 2012;160C:104
- Hogart A, Wu D, LaSalle JM, Schanen NC. The comorbidity of autism with the genomic disorders of chromosome 15q2-q13. Neurobiol Dis 2010;38(2):181-91.
- Howlin P, Goode S, Hotton J, Rutter M. Adult outcome for children with autism. J Child Psychol Psychiatr 2004;45(2):212-29.
- Jacquemont ML, Sanlaville D, Redon R, Raoul O, Cormier-Daire V, Lyonnet S, et al. Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet 2006;43:843-9.
- Knoester M, Helmerhost FM, van der Westerlaken LAJ, Walther FJ, Veen S, on behalf of the Leiden Artificial Reproductive Techniques Follow-Up Project (L-art-FUP). Matched follow-up study of 58-year-old ICSI singletons: child behaviour, parenting stress, and child (health-related) quality of life. Hum Repr 2007;22(12):3098-107.
- Kogan MD, Blumberg SJ, Schieve LA, Boyle CA, Perrin JM, Ghandour RM, et al. Prevalance of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics 2009;124:1395-404.
- Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008;82:477-88.
- Miles JH, McCathren RB, Stichte J, Shinawi M. Autism spectrum Disorders. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. Gene Reviews TM [Internet]. Seattle (WA): University of Washington, Seattle;1993-. 2003 Aug 27 [Updated 2010 Apr 13].
- Miles JH. Autism spectrum disorders – A genetics review. Genet Med 2011;13(4):278-94.
- Miller MT, Strömland K, Ventura L, Johansson M, Bandim JM, Gillberg C. Autism with ophthalmologic malformations: The plot thickens. Trans Am Ophthalmol Soc 2004;102:107-21.
- Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L. Recurrence risk for autism spectrum disorders: A baby siblings research consortium study. Pediatrics 2011;128(3):e488-93.
- Pickles A, Starr E, Kazak S, Bolton P, Papanikolaou K, Bailey A, et al. Variable expression of the autism broader phenotype: Findings from extended pedigrees. J Child Psychol Psychiarty 2000;41(4):491-502.
- Reddy KS. Cytogenetic abnormalities and fragile-x syndrome in autistic spectrum disorder. BMC Med Genet 2005;6:3 doi:10.1186/1471-2350-6-3.
- Schattuck PT. Diagnostic substitution and changing autism prevalance. Pediatrics 2006;117:1438-40.
- Sebat J, Lakshmi B, Malhotra D, Troge J, LeseMartin C, Walsh T, et al. Strong association of de novo copy number mutations with autism. Science 2007;316(5823):445-9.
- Shinawi M, Schaaf CP, Bhaat SS, Xia Z, Patel A, Cheung SW, et al. A small recurrent deletion within 15q3 is associated with a range of neurodevelopmental phenotypes. Nat Genet 2009;41(12):1269-71.
- Voineagu I. Gene expression studies in autism: Moving from the genome to the transcriptome and beyond. Neurobiol Dis 2012;45:69-75.
- Williams EL, Casanova MF. Above genetics: lessons from cerebral development in autism. Transl Neurosci 2011;2(2):106-20.
Öz
Otizm yaklaşık yüz kişiden birini etkilemektedir. Oluşum nedenleri arasında genetik etmenlerin önemli rol oynadığı bu hastalıktaki temel problemler, sosyal ilişkiler, dil gelişimi ve iletişim becerilerinde kendini göstermektedir. Hastaların büyük kısmında tekrarlayıcı hareketler ve ilgi alanlarında ciddi kısıtlılık söz konusudur. Otizmli hastaların %75’inde gözlenen entellektüel yetersizlik, yaşam boyu önemli düzeyde sosyal ve eğitsel desteğe gereksinim yarattığından ciddi bir toplumsal sağlık problemi oluşturmaktadır. Otizm etyolojisinin aydınlatılmasına yönelik çalışmalardan elde edilen verilerde, hemen hemen tüm kromozomlarda gözlenen bazı sitogenetik düzensizlikler ile otizm arasında anlamlı bağlantılar bulunduğu gösterilmiştir. Son yıllarda moleküler genetikte yaşanan teknolojik ilerlemeler daha ince düzeyde değerlendirmeler yapılmasına olanak sağlamış ve bununla birlikte genomdaki çeşitli kopya sayısı değişikliklerinin otizmle önemli ilişkisi bulunduğu belirlenmiştir. Konvansiyonel sitogenetik analizlerle belirlenebilen bazı kromozom anomalileri, moleküler yöntemlerle gözlenebilen çeşitli kopya sayısı değişikliklerinin otizmle ilişkilendirilmesinin yanısıra tek gen mutasyonlarının neden olduğu genetik sendromların çoğunda da otizm belirtileri bulunmaktadır. Etyopatogenezin aydınlatılması uygun tedavinin planlanması, hastalığın seyri ve tekrarlama riskiyle ilişkili genetik danışma verilmesi açısından büyük önem taşımaktadır. Otizm tanısında kullanılacak sitogenetik ve moleküler testler genetik ayrıntılardan oluşturulmuş belli algoritmaların sonucuna göre uygulanmalı, ayırıcı tanıda genetik düzensizlikler ve otizmle ilişkili sendromlar belirlenmelidir. Böylece hem potansiyel komplikasyonların önüne geçmek, hem de uygun tedavinin başlatılması mümkün olabilir. Sonuç olarak, otizm hastalarına tıbbi yaklaşım bir ekip tarafından yapılmalı ve bu ekibin içinde hasta yaş gurubuna uygun klinisyen, psikolog/pedagog, fizyoterapist, konuşma terapistinin yanısıra tıbbi genetik uzmanları bulunmalıdır.
Anahtar Kelimeler
Kaynakça
- Akçakın M. [Development defining in autism spectrum disorders]. Turkiye Klinikleri J Pediatr Sci 2007;3(3):14-24.
- American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association.
- Atladottir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends in reported diagnoses of childhood neuropsychiatric disorders. Arch Pediatr Adolesc Med 2007;161:193-8.
- Bhandari A, Sandlow JI, Brannigan RE. Androlog summary: Risks to offspring associated with advanced paternal age. J Androl 2011;32(2):121-2.
- Carter AS, Black DO, Tewani S, Connoly CE, Kadlec MB, Tager-Flusberh H. Sex differences in toddlers with autism spectrum disorders. J Autism Dev Disord 2007;37:86-97.
- Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children. JAMA 2001;285:3093-9.
- DiCicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C, et al. The developmental neurobiology of autism spectrum disorder. J Neurosci 2006;26(26):6897-906.
- Erden G, Akçakın M, Gümüş Doğan D, Öztürk Erdem İ. [Pediatricians and autism: Difficulties in Diagnosis]. Turkiye Klinikleri J Pediatr Sci 2010;19(1):9-15.
- Fitzpatrick M. The end of the road for the campaign against MMR. Br J Gen Pract 2007;57(541):679.
- Gillberg C, Gillberg C, Rastam M, ,Wentz E. The Asperger syndrome (and high-functioning autism) diagnostic interview (ASDI): a preliminary study of a new structured clinical interview. Autism 2001;5(1):57-66.
- Gurrieri F. Working up autism: The practical role of medical genetics. Am J Med Genet 2012;160C:104
- Hogart A, Wu D, LaSalle JM, Schanen NC. The comorbidity of autism with the genomic disorders of chromosome 15q2-q13. Neurobiol Dis 2010;38(2):181-91.
- Howlin P, Goode S, Hotton J, Rutter M. Adult outcome for children with autism. J Child Psychol Psychiatr 2004;45(2):212-29.
- Jacquemont ML, Sanlaville D, Redon R, Raoul O, Cormier-Daire V, Lyonnet S, et al. Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet 2006;43:843-9.
- Knoester M, Helmerhost FM, van der Westerlaken LAJ, Walther FJ, Veen S, on behalf of the Leiden Artificial Reproductive Techniques Follow-Up Project (L-art-FUP). Matched follow-up study of 58-year-old ICSI singletons: child behaviour, parenting stress, and child (health-related) quality of life. Hum Repr 2007;22(12):3098-107.
- Kogan MD, Blumberg SJ, Schieve LA, Boyle CA, Perrin JM, Ghandour RM, et al. Prevalance of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics 2009;124:1395-404.
- Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008;82:477-88.
- Miles JH, McCathren RB, Stichte J, Shinawi M. Autism spectrum Disorders. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. Gene Reviews TM [Internet]. Seattle (WA): University of Washington, Seattle;1993-. 2003 Aug 27 [Updated 2010 Apr 13].
- Miles JH. Autism spectrum disorders – A genetics review. Genet Med 2011;13(4):278-94.
- Miller MT, Strömland K, Ventura L, Johansson M, Bandim JM, Gillberg C. Autism with ophthalmologic malformations: The plot thickens. Trans Am Ophthalmol Soc 2004;102:107-21.
- Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L. Recurrence risk for autism spectrum disorders: A baby siblings research consortium study. Pediatrics 2011;128(3):e488-93.
- Pickles A, Starr E, Kazak S, Bolton P, Papanikolaou K, Bailey A, et al. Variable expression of the autism broader phenotype: Findings from extended pedigrees. J Child Psychol Psychiarty 2000;41(4):491-502.
- Reddy KS. Cytogenetic abnormalities and fragile-x syndrome in autistic spectrum disorder. BMC Med Genet 2005;6:3 doi:10.1186/1471-2350-6-3.
- Schattuck PT. Diagnostic substitution and changing autism prevalance. Pediatrics 2006;117:1438-40.
- Sebat J, Lakshmi B, Malhotra D, Troge J, LeseMartin C, Walsh T, et al. Strong association of de novo copy number mutations with autism. Science 2007;316(5823):445-9.
- Shinawi M, Schaaf CP, Bhaat SS, Xia Z, Patel A, Cheung SW, et al. A small recurrent deletion within 15q3 is associated with a range of neurodevelopmental phenotypes. Nat Genet 2009;41(12):1269-71.
- Voineagu I. Gene expression studies in autism: Moving from the genome to the transcriptome and beyond. Neurobiol Dis 2012;45:69-75.
- Williams EL, Casanova MF. Above genetics: lessons from cerebral development in autism. Transl Neurosci 2011;2(2):106-20.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Derleme |
| Yazarlar | |
| Yayımlanma Tarihi | 21 Mayıs 2014 |
| Gönderilme Tarihi | 1 Ekim 2012 |
| Yayımlandığı Sayı | Yıl 2013 Cilt: 76 Sayı: 4 |
Kaynak Göster
Contact information and address
Addressi: İ.Ü. İstanbul Tıp Fakültesi Dekanlığı, Turgut Özal Cad. 34093 Çapa, Fatih, İstanbul, TÜRKİYE
Email: itfdergisi@istanbul.edu.tr
Phone: +90 212 414 21 61