DOI QR코드

DOI QR Code

The first Korean case of Waardenburg-Shah syndrome with novel endothelin receptor type B mutations

  • Lee, Eun Sun (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine) ;
  • Ko, Jung Min (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine) ;
  • Moon, Jin Su (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine)
  • Received : 2017.12.12
  • Accepted : 2017.12.18
  • Published : 2017.12.31

Abstract

Waardenburg syndrome (WS) is a rare genetic disorder, including clinical features of pigmentary abnormalities of irides, skin, hair and sensorineural hearing loss and facial dysmorphism. Among the four types, WS type IV (Waardenburg-Shah syndrome) additionally represents Hirschsprung's disease. Mutations in the SOX10, END3, or EDNRB genes are known to cause WS type IV. Here, we report a 6 year-old girl who was diagnosed as WS type IV by typical clinical manifestations, including skin hypopigmentation, heterochromia of both irides, unilateral sensorineural hearing loss, mild developmental delay and Hirschsprung's disease. The diagnosis was confirmed by molecular genetic analysis of EDNRB. Two novel EDNRB mutations were identified, and each mutation was segregated from each of her parents. During the follow-up period, the patient underwent a surgery for spleen torsion and was medically managed due to recurrent enterocolitis. Also, she suffered from impaired immunity including Hirschsprung's associated enterocolitis.

Keywords

References

  1. Waardenburg PJ. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 1951;3:195-253.
  2. Nayak CS, Isaacson G. Worldwide distribution of Waardenburg syndrome. Ann Otol Rhinol Laryngol 2003;112:817-20. https://doi.org/10.1177/000348940311200913
  3. Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Hum Mutat 2010;31:391-406. https://doi.org/10.1002/humu.21211
  4. Sharma K, Arora A. Waardenburg syndrome: a case study of two patients. Indian J Otolaryngol Head Neck Surg 2015;67:324-8. https://doi.org/10.1007/s12070-015-0870-3
  5. McCallion AS, Chakravarti A. EDNRB/EDN3 and Hirschsprung disease type II. Pigment Cell Res 2001;14:161-9. https://doi.org/10.1034/j.1600-0749.2001.140305.x
  6. Shah KN, Dalal SJ, Desai MP, Sheth PN, Joshi NC, Ambani LM. White forelock, pigmentary disorder of irides, and long segment Hirschsprung disease: possible variant of Waardenburg syndrome. J Pediatr 1981;99:432-5. https://doi.org/10.1016/S0022-3476(81)80339-3
  7. Doubaj Y, Pingault V, Elalaoui SC, Ratbi I, Azouz M, Zerhouni H, et al. A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome. Mol Syndromol 2015;6:44-9.
  8. Arai H, Nakao K, Takaya K, Hosoda K, Ogawa Y, Nakanishi S, et al. The human endothelin-B receptor gene. Structural organization and chromosomal assignment. J Biol Chem 1993;268:3463-70.
  9. Tuysuz B, Collin A, Arapoglu M, Suyugul N. Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. Am J Med Genet A 2009;149A:2290-5. https://doi.org/10.1002/ajmg.a.33031
  10. Puffenberger EG, Kauffman ER, Bolk S, Matise TC, Washington SS, Angrist M, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet 1994;3:1217-25. https://doi.org/10.1093/hmg/3.8.1217
  11. Sangkhathat S, Chiengkriwate P, Kusafuka T, Patrapinyokul S, Fukuzawa M. Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease. Pediatr Surg Int 2005;21:960-3. https://doi.org/10.1007/s00383-005-1553-z
  12. Brown S, Gersen S, Anyane-Yeboa K, Warburton D. Preliminary definition of a "critical region" of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am J Med Genet 1993;45:52-9. https://doi.org/10.1002/ajmg.1320450115
  13. Garcia-Rodriguez E, Garcia-Garcia E, Perez-Sanchez A, Pavon-Delgado A. A new observation of 13q deletion syndrome: severe undescribed features. Genet Couns 2015;26:213-7.
  14. Demehri FR, Halaweish IF, Coran AG, Teitelbaum DH. Hirschsprungassociated enterocolitis: pathogenesis, treatment and prevention. Pediatr Surg Int 2013;29:873-81. https://doi.org/10.1007/s00383-013-3353-1
  15. Gosain A, Barlow-Anacker AJ, Erickson CS, Pierre JF, Heneghan AF, Epstein ML, et al. Impaired cellular immunity in the murine neural crest conditional deletion of endothelin receptor-B model of Hirschsprung's disease. PLoS One 2015;10:e0128822. https://doi.org/10.1371/journal.pone.0128822
  16. Gosain A, Brinkman AS. Hirschsprung's associated enterocolitis. Curr Opin Pediatr 2015;27:364-9. https://doi.org/10.1097/MOP.0000000000000210