Síndrome de Angelman: causa frequentemente não reconhecida de deficiência mental e epilepsia. relato de caso

Fridman, Cintia; Kok, Fernando; Diament, Aron; Koiffmann, Célia P.

doi:10.1590/S0004-282X1997000200025

Resumos

Os autores descrevem um caso típico de síndrome de Angelman. A paciente apresenta atraso de desenvolvimento neuropsicomotor, deficiência mental, macrostomia, dentes espaçados, convulsões, ausência de fala, andar com a base alargada e instável, crises de risos. Os estudos citogenéticos e moleculares revelaram deleção do segmento 15q11ql3 de origem materna, confirmando o diagnóstico clínico de síndrome de Angelman.

síndrome de Angelman; cromossomo 15; imprinting genômico

The authors describe the case of a typical Angelman syndrome patient. The proband presents developmental delay, mental retardation, macrostomia, wide-spaced teeth, seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic and molecular studies showed a maternal deletion of 15q11q13. These results are in agreement with the clinical diagnosis of Angelman syndrome.

Angelman syndrome; chromosome 15; genomic imprinting

Síndrome de Angelman: causa frequentemente não reconhecida de deficiência mental e epilepsia. relato de caso

Angelman syndrome: a frequently undiagnosed cause of mental retardation and epilepsy. case report

Cintia Fridman^I; Fernando Kok^II; Aron Diament^III; Célia P. Koiffmann^IV

^IUnidade de Aconselhamento Genético do Departamento de Biologia do Instituto de Biociências da Universidade de São Paulo (IBUSP): Mestre em Biologia/Genética

^IIServiço de Neurologia Infantil da Clínica Neurológica do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP): Médico Assistente

^IIIServiço de Neurologia Infantil da Clínica Neurológica do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP): Chefe do Serviço

^IVUnidade de Aconselhamento Genético do Departamento de Biologia do Instituto de Biociências da Universidade de São Paulo (IBUSP): Professor Doutor

RESUMO

Os autores descrevem um caso típico de síndrome de Angelman. A paciente apresenta atraso de desenvolvimento neuropsicomotor, deficiência mental, macrostomia, dentes espaçados, convulsões, ausência de fala, andar com a base alargada e instável, crises de risos. Os estudos citogenéticos e moleculares revelaram deleção do segmento 15q11ql3 de origem materna, confirmando o diagnóstico clínico de síndrome de Angelman.

Palavras-chave: síndrome de Angelman, cromossomo 15, imprinting genômico.

ABSTRACT

The authors describe the case of a typical Angelman syndrome patient. The proband presents developmental delay, mental retardation, macrostomia, wide-spaced teeth, seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic and molecular studies showed a maternal deletion of 15q11q13. These results are in agreement with the clinical diagnosis of Angelman syndrome.

Key-words: Angelman syndrome, chromosome 15, genomic imprinting.

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AGRADECIMENTOS

O presente trabalho foi realizado com suporte financeiro da FAPESP e do CNPq.

Aceite: 28-fevereiro-1997.

Cintia Fridman - Unidade de Aconselhamento Genético, IBUSP - Caixa Postal 11461 - 05422-970 São Paulo SP - Brasil. E-mail: cfiidman@usp.br

1. Angelman H. "Puppet" children: a report on three cases. Develop Med Child Neurol 1965;7:681 -688.
2. Bottani A, Robinson WP, DeLozier-Blanchet CD, Engel E, Morris MA, Schmitt B, Thun-Hohenstein L, Schinzel A. Angelman syndrome due to paternal uniparental disomy of chromosome 15: a milder phenotype? Am J Med Genet 1994-,51:35-40.
3. Boyd SG, Harden A, Patton MA. The EEG in early diagnosis of the Angelman (happy puppet) syndrome. Eur J Pediatr 1988;147:508-513.2
4. Buiting K, Saitoh S, Gross S, Dittrich B, Schwartz S, Nicholls RD, Horsthemke B. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting center on human chromosome 15. Nature Genet 1995;9:395-400.
5. Chan C-TJ, Clayton-Smith J, Cheng X-J, Buxton J, Webb T, Pembrey ME, Malcolm S. Molecular mechanisms in Angelman syndrome: a survey of 93 patients. J Med Genet 1993;30:895-902.
6. Clayton-Smith J. Angelman's syndrome. Arch Dis Childh 1992,67:889-890.
7. Clayton-Smith J, Pembrey ME. Angelman syndrome. J Med Genet 1992;29:412-415.
8. Freeman SB, May KM, Pettay D, Fernhoff PM, Hassold TJ. Paternal uniparental disomy in a child with a balanced 15,15 translocation and Angelman syndrome. Am J Med Genet 1993;45:625-630.
9. Fridman C. Estudo genético-clínico de síndromes associadas à região 15q11-13, São Paulo, 1995. Dissertação de Mestrado, Departamento de Biologia, Instituto de Biociências da Universidade de São Paulo.
10. Fryburg JS, Breg WR, Lindgren V. Diagnosis of Angelman syndrome in infants. Am J Med Genet 1991;38:58-64.
11. Gillessen-Kaesbach G, Albrecht B, Passarge E, Horsthemke B. Further patient with Angelman syndrome due to paternal disomy of chromosome 15 and a milder phenotype. Am J Med Genet 1995;56:328-329.
12. Knoll JHM, Glatt KA. Nicholls RD, Malcolm S, Lalande M. Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. Am J Hum Genet 1991;48:16-21.
13. Knoll JHM, Nicholls RD, Magenis RE, Graham JM Jr, Laiande M, Latt SA. Angelman and Prader-Willi syndromes shares a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet 1989;32:285-290.
14. Magenis RE, Brown MG, Lacy DA, Budden S, LaFranchi S. Is Angelman syndrome an alternative result of del (15)(q11q13)? Am J Med Genet 1987;28:829-838.
15. Magenis RE, Toth-Fejel S. Allen U, Black M, Brown MG, Budden S, Cohen R, Friedman JM, Kalousek D, Zonana J, Lacy D, LaFranchi S, Lahr M, Macfarlane J, Williams CPS. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am J Med Genet 1990;35:333-349.
16. Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, Armour JAL, Jeffreys AJ, Pembrey ME. Uniparental paternal disomy in Angelman's syndrome. Lancet 1991 ;337:694-697.
17. Nicholls RD. Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: a review. Am J Med Genet 1993;46:16-25.
18. Nicholls RD. New insights reveal complex mechanisms involved in genomic imprinting. Am J Hum Genet 1994;54:733-740.
19. Nicholls RD, Pai GS, Gottlieb W, Cantú ES. Paternal uniparental disomy of chromosome 15 in a child with Angclman syndrome. Ann Neurol 1992;32:512-518.
20. Pembrey M. Fenncll SJ, Van Den Berghe J, Fitchett M, Summers D, Butler L, Clarke C, Griffiths M, Thompson E, Super M, Baraitser M. The association of Angelman's syndrome with deletions within 15q11-13. J Med Genet 1989;26:73-77.
21. Reis A, Dittrich B, Greger V, Buiting K, Lalande M, Gillessen-Kaesbach G, Anvret M, Horsthemke B. Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. Am J Hum Genet 1994:54:741-747.
22. Robb SA, Pohl KRE. Baraitser M, Wilson J, Brett EM. The 'happy puppet' syndrome of Angelman: review of the clinical features. Arch Dis Childh 1989;64:83-86.
23. Saitoh S, Buiting K, Rogan PK, Buxton JL, Driscoll DJ, Arnemann J, Konig R, Malcolm S, Horsthemke B, Nicholls RD. Minimal definition of the imprinting center and fixation of a chromosome 15q1l-ql3 epigenotype by imprinting mutations. Proc Natl Acad Sci USA 1996;93:7811 -7815.
24. Smects DFCM, Hamel BCJ, Nelen MR. Smeets HJM, Smits APT, Ropers H-H, van Oast BA. Prader-Willi syndrome and Angelman syndrome in cousins from a family with translocation between chromosomes 6 and 15. N Engl JMed 1992;326:807-811.
25. Webb T, Malcolm S, Pembrey ME, Clayton-Smith J. Inheritance of parental chromosomes 15 in Angelman syndrome: implications for the family. Genetic Counseling 1993;4:1 -6.
26. Williams CA, Angelman H, Clayton-Smith J, Driscoll DJ, Hendrickson JE, Knoll JHM, Magenis RE. Schinzel A, WagstaffJ, Whidden EM, Zori RT. Angelman syndrome: consensus for diagnostic criteria. Am J Med Genet 1995:56:237-238.
27. Willems PJ. Dijkstra I, Brouwer OF, Smit GPA. Recurrence risk in Angelman ("happy puppet") syndrome. Am J Med Genet 1987;27:773-780.
28. Zori RT, Hendrickson J, Woolven S, Whidden EM, Gray B, Williams CA. Angelman syndrome: clinical profile. J Child Neurol 1992:7:270-280.

Datas de Publicação

Publicação nesta coleção
10 Nov 2010
Data do Fascículo
Jun 1997

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Angelman H. "Puppet" children: a report on three cases. Develop Med Child Neurol 1965;7:681 -688.

[2] 2. Bottani A, Robinson WP, DeLozier-Blanchet CD, Engel E, Morris MA, Schmitt B, Thun-Hohenstein L, Schinzel A. Angelman syndrome due to paternal uniparental disomy of chromosome 15: a milder phenotype? Am J Med Genet 1994-,51:35-40.

[3] 3. Boyd SG, Harden A, Patton MA. The EEG in early diagnosis of the Angelman (happy puppet) syndrome. Eur J Pediatr 1988;147:508-513.2

[4] 4. Buiting K, Saitoh S, Gross S, Dittrich B, Schwartz S, Nicholls RD, Horsthemke B. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting center on human chromosome 15. Nature Genet 1995;9:395-400.

[5] 5. Chan C-TJ, Clayton-Smith J, Cheng X-J, Buxton J, Webb T, Pembrey ME, Malcolm S. Molecular mechanisms in Angelman syndrome: a survey of 93 patients. J Med Genet 1993;30:895-902.

[6] 6. Clayton-Smith J. Angelman's syndrome. Arch Dis Childh 1992,67:889-890.

[7] 7. Clayton-Smith J, Pembrey ME. Angelman syndrome. J Med Genet 1992;29:412-415.

[8] 8. Freeman SB, May KM, Pettay D, Fernhoff PM, Hassold TJ. Paternal uniparental disomy in a child with a balanced 15,15 translocation and Angelman syndrome. Am J Med Genet 1993;45:625-630.

[9] 9. Fridman C. Estudo genético-clínico de síndromes associadas à região 15q11-13, São Paulo, 1995. Dissertação de Mestrado, Departamento de Biologia, Instituto de Biociências da Universidade de São Paulo.

[10] 10. Fryburg JS, Breg WR, Lindgren V. Diagnosis of Angelman syndrome in infants. Am J Med Genet 1991;38:58-64.

[11] 11. Gillessen-Kaesbach G, Albrecht B, Passarge E, Horsthemke B. Further patient with Angelman syndrome due to paternal disomy of chromosome 15 and a milder phenotype. Am J Med Genet 1995;56:328-329.

[12] 12. Knoll JHM, Glatt KA. Nicholls RD, Malcolm S, Lalande M. Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. Am J Hum Genet 1991;48:16-21.

[13] 13. Knoll JHM, Nicholls RD, Magenis RE, Graham JM Jr, Laiande M, Latt SA. Angelman and Prader-Willi syndromes shares a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet 1989;32:285-290.

[14] 14. Magenis RE, Brown MG, Lacy DA, Budden S, LaFranchi S. Is Angelman syndrome an alternative result of del (15)(q11q13)? Am J Med Genet 1987;28:829-838.

[15] 15. Magenis RE, Toth-Fejel S. Allen U, Black M, Brown MG, Budden S, Cohen R, Friedman JM, Kalousek D, Zonana J, Lacy D, LaFranchi S, Lahr M, Macfarlane J, Williams CPS. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am J Med Genet 1990;35:333-349.

[16] 16. Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, Armour JAL, Jeffreys AJ, Pembrey ME. Uniparental paternal disomy in Angelman's syndrome. Lancet 1991 ;337:694-697.

[17] 17. Nicholls RD. Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: a review. Am J Med Genet 1993;46:16-25.

[18] 18. Nicholls RD. New insights reveal complex mechanisms involved in genomic imprinting. Am J Hum Genet 1994;54:733-740.

[19] 19. Nicholls RD, Pai GS, Gottlieb W, Cantú ES. Paternal uniparental disomy of chromosome 15 in a child with Angclman syndrome. Ann Neurol 1992;32:512-518.

[20] 20. Pembrey M. Fenncll SJ, Van Den Berghe J, Fitchett M, Summers D, Butler L, Clarke C, Griffiths M, Thompson E, Super M, Baraitser M. The association of Angelman's syndrome with deletions within 15q11-13. J Med Genet 1989;26:73-77.

[21] 21. Reis A, Dittrich B, Greger V, Buiting K, Lalande M, Gillessen-Kaesbach G, Anvret M, Horsthemke B. Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. Am J Hum Genet 1994:54:741-747.

[22] 22. Robb SA, Pohl KRE. Baraitser M, Wilson J, Brett EM. The 'happy puppet' syndrome of Angelman: review of the clinical features. Arch Dis Childh 1989;64:83-86.

[23] 23. Saitoh S, Buiting K, Rogan PK, Buxton JL, Driscoll DJ, Arnemann J, Konig R, Malcolm S, Horsthemke B, Nicholls RD. Minimal definition of the imprinting center and fixation of a chromosome 15q1l-ql3 epigenotype by imprinting mutations. Proc Natl Acad Sci USA 1996;93:7811 -7815.

[24] 24. Smects DFCM, Hamel BCJ, Nelen MR. Smeets HJM, Smits APT, Ropers H-H, van Oast BA. Prader-Willi syndrome and Angelman syndrome in cousins from a family with translocation between chromosomes 6 and 15. N Engl JMed 1992;326:807-811.

[25] 25. Webb T, Malcolm S, Pembrey ME, Clayton-Smith J. Inheritance of parental chromosomes 15 in Angelman syndrome: implications for the family. Genetic Counseling 1993;4:1 -6.

[26] 26. Williams CA, Angelman H, Clayton-Smith J, Driscoll DJ, Hendrickson JE, Knoll JHM, Magenis RE. Schinzel A, WagstaffJ, Whidden EM, Zori RT. Angelman syndrome: consensus for diagnostic criteria. Am J Med Genet 1995:56:237-238.

[27] 27. Willems PJ. Dijkstra I, Brouwer OF, Smit GPA. Recurrence risk in Angelman ("happy puppet") syndrome. Am J Med Genet 1987;27:773-780.

[28] 28. Zori RT, Hendrickson J, Woolven S, Whidden EM, Gray B, Williams CA. Angelman syndrome: clinical profile. J Child Neurol 1992:7:270-280.