A case of inversion of chromosome 4 and an unbalanced transloca- tion between the short arm of chromosome 4 and long arm of chromosome 18 in a girl: evolution of clinical and electroencephalographic manifestations

We report a case of a girl with a chromosomal disorder that has never been described in the literature: inversion of chromosome 4 with an unbalanced translocation between the short arm of chromosome 4 and long arm of chromosome 18. Clinical manifestations of this syndrome included severe growth retardation, very slow weight gain, optic nerve hypoplasia, pronounced delay in mental and motor development, and epilepsy with focal hemiclonic fever-related seizures of varying location. The patient has multiple stigmas of dysembryogenesis, but no abnormalities in the development of internal organs. The somatic status is complicated by chronic liquid aspiration and sleep apnea. Magnetic resonance imaging has demonstrated agenesis of the corpus callosum. In this article, we have summarized the results of clinical observation and electroencephalography findings obtained during several years. The type of epilepsy in this girl does not match Wolf–Hirschhorn syndrome (which is determined by her karyotype), but is similar to epilepsy in patients with aberrations of the long arm of chromosome 18.

1. Beaujard M.P., Jouannic J.M., Bessières B. et al. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf–Hirschhorn syndrome phenotype. Prenat Diagn 2005;25(6):451–5.

2. Chen C.P., Su Y.N., Chen Y.Y. et al. Wolf–Hirschhorn (4p–) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion. Taiwan J Obstet Gynecol 2011;50(4):506–11. DOI: 10.1016/j.tjog.2011.10.019.

3. Hirsch B., Baldinger S. Pericentric inversion of chromosome 4 giving rise to dup(4p) and dup(4q) recombinants within a single kindred. Am J Med Genet 1993;45(1):5–8.

4. Malvestiti F., Benedicenti F., De Toffol S. et al. Recombinant chromosome 4 from a familial pericentric inversion: prenatal and adulthood wolf-hirschhorn phenotypes. Case Rep Genet 2013;2013:306098. DOI: 10.1155/2013/306098.

5. Paskulin G.A., Riegel M., Cotter P.D. et al. Inv dup del(4) (:p13→p16.3::p16.3→qter) in a girl without typical manifestations of Wolf–Hirschhorn syndrome. Am J Med Genet A 2009;149A(6):1302–7. DOI: 10.1002/ajmg.a.32888.

6. Puig M., Casillas S., Villatoro S., Cáceres M. Human inversions and their functional consequences. Brief Funct Genomics 2015;14(5):369–79. DOI: 10.1093/bfgp/elv020.

7. Stipoljev F., Stanojevic M., Kurjak A. Familial pericentric inversion of chromosome 4: inv(4)(p16.1q12). Clin Genet 2002:61:386–8.

8. Verrotti A., Carelli A., di Genova L., Striano P. Epilepsy and chromosome 18 abnormalities: A review. Seizure 2015;32:78–8. DOI: 10.1016/j.seizure.2015.09.013.

9. Villa A., Urioste M., Carrascosa M.C. et al. Pericentric inversions of chromosome 4: report of a new family and review of the literature. Clin Genet 1995;48(5):255–60.

10. Zollino M., Murdolo M., Marangi G. et al. On the nosology and pathogenesis of Wolf–Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Clin Genet C 2008;148(4):257–69.