International Journal of Infertility & Fetal Medicine

Register      Login

VOLUME 12 , ISSUE 3 ( September-December, 2021 ) > List of Articles

Original Article

Phenotypic Features and Inheritance Pattern of Emanuel Syndrome: An Indian Perspective

Vandana Kamath, Vivi M Srivastava, Mary P Chacko, Yuvarani S, Samuel P Oommen, Beena Koshy

Keywords : der(22)t(11,22)(q23,q11.2),t(11,22), Emanuel syndrome, Inheritance, Low copy repeats quality of life

Citation Information : Kamath V, Srivastava VM, Chacko MP, S Y, Oommen SP, Koshy B. Phenotypic Features and Inheritance Pattern of Emanuel Syndrome: An Indian Perspective. Int J Infertil Fetal Med 2021; 12 (3):60-65.

DOI: 10.5005/jp-journals-10016-1228

License: CC BY-NC 4.0

Published Online: 30-09-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Aim and objective: To study the phenotypic features and inheritance patterns in children diagnosed with Emanuel syndrome (ES). Materials and methods: All children who underwent cytogenetic analysis at the Christian Medical College, Vellore and whose karyotypes showed the supernumerary chromosome 22 derived from an unbalanced translocation (11;22)(q23;q11.2) were included. Karyotypes of family members were retrieved from hospital records. Metaphases were obtained from phytohemagglutinin-stimulated peripheral blood cultured using standard protocols. At least 20 Giemsa-banded metaphases were analyzed and reported in accordance with the International System for Human Cytogenomic Nomenclature. The clinical features and imaging findings were retrieved from our medical records. The karyotype findings of parents and family history including the obstetric history of all mothers were recorded. Results: There were eight children, three girls and five boys, all of whom were from unrelated families. The age at presentation ranged from 8 months to 8 years of age. Three families presented with significant family history in the form of previous sibling deaths, recurrent abortions in the mother, and maternal siblings’ death. All eight children presented with global developmental delay. Preauricular sinus was found in six children (6/8,75%), while microcephaly and hypotonia in five each (5/8,62.5%). More than half of our children presented with structural cardiac and brain malformations. In three children, the der(22) was found to have originated from a maternal source of the t(11;22). All three mothers who harbored this translocation were phenotypically normal. Conclusion: The characteristic clinical features of ES found in our study included preauricular sinus, microcephaly, hypotonia, cardiac defects, and structural brain malformations. The maternal source of the t(11;22) was the commonest mode of inheritance among children diagnosed with ES. Clinical significance: Emanuel syndrome is a rare syndrome and it is extremely important to identify the phenotypic features of this clinical entity since early intervention can aid in appropriate counselling and offering prenatal testing. The majority of children diagnosed with ES were found to have inherited this genetic defect due to a translocation (11;22) running in the family. Hence, a clear understanding of the reproductive outcomes of the t(11;22) is of vital importance in counseling the family members and offering prenatal testing.

  1. Carter MT, St. Pierre SA, Zackai EH, et al. Phenotypic delineation of Emanuel syndrome (supernumerary derivative 22 syndrome): clinical features of 63 individuals. Am J Med Genet Part A 2009;149A(8):1712–1721. DOI: 10.1002/ajmg.a.32957.
  2. Fraccaro M, Lindsten J, Ford CE, et al. The 11q;22q translocation: a European collaborative analysis of 43 cases. Hum Genet 1980;56(1):21–51. DOI: 10.1007/BF00281567.
  3. Iselius L, Lindsten J, Aurias A, et al. The 11q;22q translocation: a collaborative study of 20 new cases and analysis of 110 families. Hum Genet 1983;64(4):343–355. DOI: 10.1007/BF00292366.
  4. Zackai EH, Emanuel BS. Site-specific reciprocal translocation, t(11;22) (q23;q11), in several unrelated families with 3:1 meiotic disjunction. Am J Med Genet 1980;7(4):507–521. DOI: 10.1002/ajmg.1320070412.
  5. McGowan-Jordan J, Simon A, Schmid M. An International System for Human Cytogenomic Nomenclature (2016). Basel: S. Karger; 2016. pp. 37–38.
  6. Arsham MS, Barch MJ, Lawce HJ. The AGT cytogenetics laboratory manual. 4th ed., New Jersey: John Wiley & Sons, vol. 98–108, 2016. pp. 280–281.
  7. Uchida IA, Ray M, McRae KN, et al. Familial occurrence of trisomy 22. Am J Hum Genet 1968;20(2):107–118.
  8. Penchaszadeh VB, Coco R. Trisomy 22: two new cases and delineation of the phenotype. J Med Genet 1975;12(2):193–199. DOI: 10.1136/jmg.12.2.193.
  9. Alfi OS, Sanger RG, Donnell GM. Trisomy 22: a clinically identifiable syndrome. Birth Defects Orig Artic Ser 1975;11(5):241–245.
  10. Kessel E, Pfeiffer RA. 47,XY,+der(11;22)(q23;q12) following balanced translocation t(11;22)(q23;q12)mat. Remarks on the problem of trisomy 22. Hum Genet 1977;37(1):111–116. DOI: 10.1007/BF00293781.
  11. Shaikh TH, Budarf ML, Celle L, et al. Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families. Am J Hum Genet 1999;65(6):1595–1607. DOI: 10.1086/302666.
  12. Emanuel BS, Zackai EH, Aronson MM, et al. Abnormal chromosome 22 and recurrence of trisomy-22 syndrome. J Med Genet 1976;13(6):501–506. DOI: 10.1136/jmg.13.6.501.
  13. Medne L, Zackai EH, Emanuel BS. Emanuel Syndrome. Gene Reviews at Gene Tests: Medical Genetics Information Resource (database online). Apr 202007 [December 22, 2008].
  14. Gardner RJM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. 4th ed., New York: Oxford; 2012. pp. 102–107.
  15. Armstrong SJ, Goldman ASH, Speed RM, et al. Meiotic studies of a human male carrier of the common translocation, t(11;22), suggests postzygotic selection rather than preferential 3:1 MI segregation as the cause of liveborn offspring with an unbalanced translocation. Am J Hum Genet 2000;67(3):601–609. DOI: 10.1086/303052.
  16. Mc Clatchey KD. Clinical laboratory medicine. 2nd ed., Lippincot Williams & Wilkins, Issue 1 2002. p. 622. DOI: 10.1080/15548627.2015.1100356.
  17. Kurahashi H, Inagaki H, Ohye T, et al. The constitutional t(11;22): implications for a novel mechanism responsible for gross chromosomal rearrangements. Clin Genet 2010;78(4):299–309. DOI: 10.1111/j.1399-0004.2010.01445.x.
  18. Kurahashi H, Emanuel B. Unexpectedly high rate of de novo constitutional t(11;22) translocations in sperm from normal males. Nat Genet 2001(29):139–140. DOI: 10.1038/ng1001-139.
  19. Kurahashi H, Shaikh TH, Zackai EH, et al. Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22). Am J Hum Genet 2000;67(3):763–768. DOI: 10.1086/303054.
  20. Inagaki H, Ohye T, Kogo H, et al. Chromosomal instability mediated by non-B DNA: cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans. Genome Res 2009;19(2):191–198. DOI: 10.1101/gr.079244.108.
  21. Puliti A, Rizzato C, Conti V, et al. Low-copy repeats on chromosome 22q11.2 show replication timing switches, DNA flexibility peaks and stree inducible asynchrony, sharing instability features with fragile sites. Mutat Res 2010;686(1-2):74–83. DOI: 10.1016/j.mrfmmm.2010.01.021.
  22. Kamath V, Srivastava VM, Yuvarani S, et al., The Constitutional Balanced Translocation t(11;22)(q23;q11.2)-An Indian Account.
  23. Lin AL, Bernar J, Chin AJ, et al. Congenital heart disease in supernumerary der(22), t(11;22) syndrome. Clin Genet 1986;29(4):269–275. DOI: 10.1111/j.1399-0004.1986.tb01254.x.
  24. Giraud F, Mattei JF, Mattei MG, et al. Trisomie partielle 11q et translocation familiale 11-22. Humangenetik 1975;28(4):343–347.
  25. Pallotta E, Fusilli P, Ehresmann T, et al. Cerebral defects confirm midline developmental field disturbances in supernumerary der(22),t(11;22) syndrome. Clin Genet 1996;50(5):411–416. DOI: 10.1111/j.1399-0004.1996.tb02398.x.
  26. Pihko H, Therman E, Uchida IA. Partial 11q trisomy syndrome. Hum Genet 1981;58(2):129–134. DOI: 10.1007/BF00278696.
  27. McDermid HE, Duncan AM, Brasch KR, et al. Characterization of the supernumerary chromosome in cat eye syndrome. Science 1986;232(4750):646–648. DOI: 10.1126/science.3961499.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.