The Miller-Dieker syndrome (MDS) is a severe neurological disorder characterized by lissencephaly, facial dysmorphies, global developmental delay and severe seizures. A deletion at 17p13.3, including the lissencephaly gene (LIS1), is usually present as part of a contiguous gene syndrome. Around 20% of case LSI1 gene is resulting from inherited balanced translocation. We present the case of a family with cryptic t(12;17) translocation identified by FISH in two generations. The proband had clinical features of MDS. The parents reported a paternal aunt deceased as a young infant due to “uncontrolled seizures and severe developmental delay. The GTG analysis of proband suggested deletion at 17p13.3 that was confirmed by FISH. The parental investigation by FISH revealed a paternal translocation involving regions 12qter and 17p13.3. This familial chromosomal rearrangement associated to MDS has modified the genetic counseling of the couple. From a very low risk of recurrence on the cases associated to a de novo del17p13.3, to a much higher risk, since it was associated to a familial translocation. This risk of recurrence, considering meiotic segregation of balanced translocation involving the 17p13.3 region is relatively high (12%) which alone would justify prenatal diagnosis. Classical and molecular cytogenetic investigations in the fetal sample were normal reassuring the couple as to a normal baby with neither 17p13.3 deletion nor carrier of the paternal translocation. This rare case identified by FISH demonstrate the need of providing molecular cytogenetic analysis for other family members; since, criptical balanced rearrangements may segregate undetected. This case evidences the importance of molecular study of parents of children with microdeletions, which could considerably improve the certainties regarding genetic counseling.
| Published in | International Journal of Genetics and Genomics (Volume 7, Issue 3) |
| DOI | 10.11648/j.ijgg.20190703.12 |
| Page(s) | 50-54 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2019. Published by Science Publishing Group |
Miller Dieker Syndrome, Cryptic Translocation, Microdeletion, Prenatal Diagnosis, Genetic Couseling
| [1] | Reiner O, Carrozzo R, Shen Y et al. Isolation of a Miller‐Dieker lissencephaly gene containing G protein beta‐subunit‐like repeats. Nature 1993: 364: 717–721. |
| [2] | Dobyns, W. B., Truwit, C. L., Ross, M. E., Matsumoto, N., Pilz, D. T., Ledbetter, D. H., Gleeson, J. G., Walsh, C. A., Barkovich, A. J. Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly. Neurology 1999; 53: 270-277. |
| [3] | Chong SS, Pack SD, Roschke AV, Tanigami A, Carrozzo R, Smith AC, Dobyns WB, Ledbetter DH. A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3. Hum Mol Genet 1997; 6: 147–155. |
| [4] | Lo Nigro, C., Chong, S. S., Smith, A. C. M., Dobyns, W. B., Carrozzo, R., Ledbetter, D. H. Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Hum. Molec. Genet. 1997; 6: 157-164. Blazejewski SM, Bennison SA, Smith TH and Toyo-oka K. Neurodevelopmental Genetic Diseases Associated With Microdeletions and Microduplications of Chromosome 17p13.3. Front. Genet 2018; 9: 80. |
| [5] | Pollin, T. I., Dobyns, W. B., Crowe, C. A., Ledbetter, D. H., Bailey-Wilson, J. E., Smith, A. C. M. Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3. Am. J. Med. Genet 1999; 85: 369-375. |
| [6] | Shaffer, L. G. et al. An International System for Human Cytogenetic Nomenclature. Basel: Karger 20132016. |
| [7] | Kato, M., Dobyns, W. B. Lissencephaly and the molecular basis of neuronal migration. Hum. Molec. Genet. 12 (R1) 2003; R89-R96. |
| [8] | Fry AE, Cushion TD, Pilz DT. The genetics of lissencephaly. Am J Med Genet Part C Semin Med Genet, 2014, 166C: 198–210. |
| [9] | Cardoso, C., Leventer, R. J., Dowling, J. J., Ward, H. L., Chung, J., Petras, K. S., Roseberry, J. A., Weiss, A. M., Das, S., Martin, C. L., Pilz, D. T., Dobyns, W. B., Ledbetter, D. H. Clinical and molecular basis of classical lissencephaly: mutations in the LIS1 gene (PAFAH1B1). Hum. Mutat 2002; 19: 4-15. |
| [10] | Cardoso, C., Leventer, R. J., Ward, H. L., Toyo-oka, K., Chung, J., Gross, A., Martin, C. L., Allanson, J., Pilz, D. T., Olney, A. H., Mutchinick, O. M., Hirotsune, S., Wynshaw-Boris, A., Dobyns, W. B., Ledbetter, D. H. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am. J. Hum. Genet 2003; 72: 918-930. |
| [11] | Pilz, D. T., Matsumoto, N., Minnerath, S., Mills, P., Gleeson, J. G., Allen, K. M., Walsh, C. A., Barkovich, A. J., Dobyns, W. B., Ledbetter, D. H., Ross, M. E. LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum. Molec. Genet. 7 1998; 2029-2037. |
| [12] | Thomas MA, Duncan AM, Bardin C, Kaloustian VM. Lissencephaly with der(17)t(17;20)(p13.3; p12.2)mat. Am J Med Genet A 2004; 124A: 292-5. |
| [13] | Van Zelderen-Bhola SL, Breslau-Siderius EJ, Beverstock GC, Stolte-Dijkstra I, de Vries LS, Stoutenbeek P, et al. Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3; q13.3) detected by fluorescence in situ hybridization. Prenat Diagn 1997; 17: 173-9. |
| [14] | Grosso S, Fichera M, Galesi O, Luciano D, Pucci L, Giardini F, et al. Bilateral periventricular nodular heterotopia and lissencephaly in an infant with unbalanced t(12;17)(q24.31; p13.3) translocation. Dev Med Child Neurol 2008; 50: 473-6. |
| [15] | Pollin TI, Dobyns WB, Crowe CA, Ledbetter DH, Bailey-Wilson JE, Smith AC. Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3. Am J Med Genet 1999: 85: 369–375. |
APA Style
Elenice Ferreira Bastos, Carlos Roberto da Fonseca, Ingrid Bendas Feres Lima, Maria de Jesus Esteves Camilo, Kleber da Silva Figueiredo, et al. (2019). Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome. International Journal of Genetics and Genomics, 7(3), 50-54. https://doi.org/10.11648/j.ijgg.20190703.12
ACS Style
Elenice Ferreira Bastos; Carlos Roberto da Fonseca; Ingrid Bendas Feres Lima; Maria de Jesus Esteves Camilo; Kleber da Silva Figueiredo, et al. Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome. Int. J. Genet. Genomics 2019, 7(3), 50-54. doi: 10.11648/j.ijgg.20190703.12
AMA Style
Elenice Ferreira Bastos, Carlos Roberto da Fonseca, Ingrid Bendas Feres Lima, Maria de Jesus Esteves Camilo, Kleber da Silva Figueiredo, et al. Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome. Int J Genet Genomics. 2019;7(3):50-54. doi: 10.11648/j.ijgg.20190703.12
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ijgg.20190703.12,
author = {Elenice Ferreira Bastos and Carlos Roberto da Fonseca and Ingrid Bendas Feres Lima and Maria de Jesus Esteves Camilo and Kleber da Silva Figueiredo and Anna Luiza Vaz Serrão and Sara Fabíola da Silva Oliveira and Lucia de Fatima Marques de Moraes and Juan Clinton Llerena Jr.},
title = {Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome},
journal = {International Journal of Genetics and Genomics},
volume = {7},
number = {3},
pages = {50-54},
doi = {10.11648/j.ijgg.20190703.12},
url = {https://doi.org/10.11648/j.ijgg.20190703.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20190703.12},
abstract = {The Miller-Dieker syndrome (MDS) is a severe neurological disorder characterized by lissencephaly, facial dysmorphies, global developmental delay and severe seizures. A deletion at 17p13.3, including the lissencephaly gene (LIS1), is usually present as part of a contiguous gene syndrome. Around 20% of case LSI1 gene is resulting from inherited balanced translocation. We present the case of a family with cryptic t(12;17) translocation identified by FISH in two generations. The proband had clinical features of MDS. The parents reported a paternal aunt deceased as a young infant due to “uncontrolled seizures and severe developmental delay. The GTG analysis of proband suggested deletion at 17p13.3 that was confirmed by FISH. The parental investigation by FISH revealed a paternal translocation involving regions 12qter and 17p13.3. This familial chromosomal rearrangement associated to MDS has modified the genetic counseling of the couple. From a very low risk of recurrence on the cases associated to a de novo del17p13.3, to a much higher risk, since it was associated to a familial translocation. This risk of recurrence, considering meiotic segregation of balanced translocation involving the 17p13.3 region is relatively high (12%) which alone would justify prenatal diagnosis. Classical and molecular cytogenetic investigations in the fetal sample were normal reassuring the couple as to a normal baby with neither 17p13.3 deletion nor carrier of the paternal translocation. This rare case identified by FISH demonstrate the need of providing molecular cytogenetic analysis for other family members; since, criptical balanced rearrangements may segregate undetected. This case evidences the importance of molecular study of parents of children with microdeletions, which could considerably improve the certainties regarding genetic counseling.},
year = {2019}
}
TY - JOUR T1 - Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome AU - Elenice Ferreira Bastos AU - Carlos Roberto da Fonseca AU - Ingrid Bendas Feres Lima AU - Maria de Jesus Esteves Camilo AU - Kleber da Silva Figueiredo AU - Anna Luiza Vaz Serrão AU - Sara Fabíola da Silva Oliveira AU - Lucia de Fatima Marques de Moraes AU - Juan Clinton Llerena Jr. Y1 - 2019/07/31 PY - 2019 N1 - https://doi.org/10.11648/j.ijgg.20190703.12 DO - 10.11648/j.ijgg.20190703.12 T2 - International Journal of Genetics and Genomics JF - International Journal of Genetics and Genomics JO - International Journal of Genetics and Genomics SP - 50 EP - 54 PB - Science Publishing Group SN - 2376-7359 UR - https://doi.org/10.11648/j.ijgg.20190703.12 AB - The Miller-Dieker syndrome (MDS) is a severe neurological disorder characterized by lissencephaly, facial dysmorphies, global developmental delay and severe seizures. A deletion at 17p13.3, including the lissencephaly gene (LIS1), is usually present as part of a contiguous gene syndrome. Around 20% of case LSI1 gene is resulting from inherited balanced translocation. We present the case of a family with cryptic t(12;17) translocation identified by FISH in two generations. The proband had clinical features of MDS. The parents reported a paternal aunt deceased as a young infant due to “uncontrolled seizures and severe developmental delay. The GTG analysis of proband suggested deletion at 17p13.3 that was confirmed by FISH. The parental investigation by FISH revealed a paternal translocation involving regions 12qter and 17p13.3. This familial chromosomal rearrangement associated to MDS has modified the genetic counseling of the couple. From a very low risk of recurrence on the cases associated to a de novo del17p13.3, to a much higher risk, since it was associated to a familial translocation. This risk of recurrence, considering meiotic segregation of balanced translocation involving the 17p13.3 region is relatively high (12%) which alone would justify prenatal diagnosis. Classical and molecular cytogenetic investigations in the fetal sample were normal reassuring the couple as to a normal baby with neither 17p13.3 deletion nor carrier of the paternal translocation. This rare case identified by FISH demonstrate the need of providing molecular cytogenetic analysis for other family members; since, criptical balanced rearrangements may segregate undetected. This case evidences the importance of molecular study of parents of children with microdeletions, which could considerably improve the certainties regarding genetic counseling. VL - 7 IS - 3 ER -
Information
Email: