Abstract
We report a Japanese boy, who showed overlapping clinical features of Miller–Dieker syndrome (lissencephaly and facial dysmorphism) and vertebral defect, anal atresia, cardiac malformation and limb anomalies (VACTERL) association. The overall clinical presentation was much more severe than that normally associated with each disorder, and the infant died on day 100 of life despite aggressive therapy. Fluorescence in situ hybridization using a commercially available LIS1 probe failed to detect a deletion, but chromosomal microarray analysis detected a 2.50-Mb microdeletion in 17p13.3 which involved partially the LIS1 gene, and thus was compatible with Miller–Dieker syndrome. It may represent an example of a combination of two congenital disorders with blended phenotypes explaining unexpectedly severe phenotypes occurring with known chromosomal rearrangements. Conclusion: We report the first case of a combination of Miller–Dieker syndrome and VACTERL association with an unusually severe phenotype.
Similar content being viewed by others
Abbreviations
- MDS:
-
Miller–Dieker syndrome
- FISH:
-
Fluorescence in situ hybridization
- NICU:
-
Neonatal intensive care unit
- CGH:
-
Comparative genomic hybridization
References
Agochukwu NB, Pineda-Alvarez DE, Keaton AA, Warren-Mora N, Raam MS, Kamat A, Chandrasekharappa SC, Solomon BD (2011) Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association. Eur J Med Genet 54:323–328
Aguinaga M, Zenteno JC, Pérez-Cano H, Morán V (2010) Sonic hedgehog mutation analysis in patients with VACTERL association. Am J Med Genet A 152A:781–783
Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH (1993) Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270:2838–2842
Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, OzmoreJR MJB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gécz J, DeLisi LE, Sebat J, King MC, Shaffer LG, Eichler EE (2010) A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet 42:203–209
Izumi K, Kuratsuji G, Ikeda K, Takahashi T, Kosaki K (2007) Partial deletion of LIS1: a pitfall in molecular diagnosis of Miller–Dieker syndrome. Pediatr Neurol 36:258–260
Nagamani SC, Zhang F, Shchelochkov OA, Bi W, Ou Z, Scaglia F, Probst FJ, Shinawi M, Eng C, Hunter JV, Sparagana S, Lagoe E, Fong CT, Pearson M, Doco-Fenzy M, Landais E, Mozelle M, Chinault AC, Patel A, Bacino CA, Sahoo T, Kang SH, Cheung SW, Lupski JR, Stankiewicz P (2009) Microdeletions including YWHAE in the Miller–Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. J Med Genet 46:825–833
Naito Y, Kimura T, Aramaki M, Izumi K, Okada Y, Suzuki H, Takahashi T, Kosaki K (2009) Caudal regression and tracheoesophageal malformation induced by adriamycin: a novel chick model of VATER association. Pediatr Res 65:607–612
Quan L, Smith DW (1973) The VATER association. Vertebral defects, anal atresia, T-E fistula with esophageal atresia, radial and renal dysplasia: a spectrum of associated defects. J Pediatr 82:104–107
Solomon BD, Bear KA, Kimonis V, de Klein A, Scott DA, Shaw-Smith C, Tibboel D, Reutter H, Giampietro PF (2012) Clinical geneticists' views of VACTERL/VATER association. Am J Med Genet A 158A:3087–3100
Veltman JA, Brunner HG (2010) Understanding variable expressivity in microdeletion syndromes. Nat Genet 42:192–193
Acknowledgments
We would like to thank Dr. Nobuhiro Suzumori at the Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Nagoya City University, for his helpful advice.
Conflict of interest
The authors have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ueda, H., Sugiura, T., Takeshita, S. et al. Combination of Miller–Dieker syndrome and VACTERL association causes extremely severe clinical presentation. Eur J Pediatr 173, 1541–1544 (2014). https://doi.org/10.1007/s00431-013-2099-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-013-2099-z