Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Dermatologic Manifestations of Waardenburg Syndrome Workup

  • Author: Lyubomir A Dourmishev, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Feb 10, 2016
 

Laboratory Studies

Waardenburg syndrome types 1 and 3 are most commonly associated with point mutations in PAX3, and type 2 is associated with MITF point mutations. Multiplex ligation-dependent probe amplification can be used to detect changes in targeted genes.[24]

Next

Other Tests

Partington used the following three interocular distances for determining the presence of dystopia cantorum (The referent value between distance of the medial canthi of the eyelids and the length between the pupils was 0.6 mm.):

  • Between the inner canthal angles
  • The near papillary distance
  • Between the other canthal angles

Arias and Mota developed the W index, as follows, for the diagnosis of lateral displacement of the inner canthi (A W index of more than 2.07 shows dystopy, while an index of less than 1.87 is normal.):

  • W index = X + Y + alb
  • Where X = [a - {0.21119c + 3.909}]/c and Y = [2a - {0.2497b + 3.909}]/b in mm
  • Distance a is between inner canthi; distance b, between pupils; and distance c, between outer canthi.
Previous
Next

Histologic Findings

Histochemical studies in the achromic skin of persons with Waardenburg syndrome show that the melanocytes are absent, or that only a few dihydroxyphenylalanine-positive cells are present.

Ultrastructural observations do not reveal melanocytes, indeterminate dendritic cells, or melanosomes in the keratinocytes of depigmented skin; however, the number of Langerhans cells in the epidermis is normal. The number of melanocytes on the edge of the leukodermas is reduced, and numerous cytoplasmic nuclear abnormalities are noted. Some melanosomes surrounded by a clear halo are found inside of vacuoles. The number of melanocytes in the hypopigmented patches of Waardenburg syndrome is dramatically reduced. These dendritic cells contained poorly melanized melanosomes.

Histopathologic examination of the inner ears of persons with Waardenburg syndrome shows absent organs of Corti, atrophy of the spinal ganglion, and reduced numbers of nerve fibers.

Previous
 
 
Contributor Information and Disclosures
Author

Lyubomir A Dourmishev, MD, PhD Associate Professor, Department of Dermatology and Venereology, Medical University of Sofia, Bulgaria

Lyubomir A Dourmishev, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology

Disclosure: Nothing to disclose.

Coauthor(s)

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Albert C Yan, MD Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.

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 Sep. 3(3):195-253. [Medline].

  2. Tachibana M. Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A. Pigment Cell Res. 1997 Feb-Apr. 10(1-2):25-33. [Medline].

  3. Wildhardt G, Zirn B, Graul-Neumann LM, Wechtenbruch J, Suckfüll M, Buske A, et al. Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics. BMJ Open. 2013. 18;3(3):[Medline].

  4. Zhang H, Luo H, Chen H, Mei L, He C, Jiang L, et al. Functionalanalysis of MITF gene mutations associated with Waardenburg syndrome type 2. FEBS. 30;586(23). 2012:4126-31. [Medline].

  5. Bondurand N, Pingault V, Goerich DE, et al. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. 2000 Aug 12. 9(13):1907-17. [Medline].

  6. Chan KK, Wong CK, Lui VC, Tam PK, Sham MH. Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation. J Cell Biochem. 2003 Oct 15. 90(3):573-85. [Medline].

  7. DeStefano AL, Cupples LA, Arnos KS, et al. Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations. Hum Genet. 1998 May. 102(5):499-506. [Medline].

  8. Dundar M, Lowther G, Colgan J, et al. A case with Waardenburg syndrome presenting with two separate translocations--one reciprocal and one complex. Clin Dysmorphol. 2001 Jan. 10(1):65-6. [Medline].

  9. Morell R, Carey ML, Lalwani AK, Friedman TB, Asher JH Jr. Three mutations in the paired homeodomain of PAX3 that cause Waardenburg syndrome type 1. Hum Hered. 1997 Jan-Feb. 47(1):38-41. [Medline].

  10. Jung HJ, Jin SA, Choi SJ, Lee SC, Yun SJ. A de novo SOX10 mutation in apatient with Waardenburg syndrome type IV. J Am Acad Dermatol. 2013. 68(6):[Medline].

  11. Oshimo T, Fukai K, Abe Y, Hozumi Y, Yokoi T, Tanaka A, et al. Pediatric case report: clinical profile of a patient with PCWH withp.Q377X nonsense mutation in the SOX10 gene. J Dermatol. 2012. 39(12):1022-5. [Medline].

  12. Sznajer Y, Coldea C, Meire F, Delpierre I, Sekhara T, Touraine RL. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease. Am J Med Genet A. 2008 Apr 15. 146A(8):1038-41. [Medline].

  13. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg syndrome. Int J Dermatol. 1999 Sep. 38(9):656-63. [Medline].

  14. Oysu C, Baserer N, Tinaz M. Audiometric manifestations of Waardenburg's syndrome. Ear Nose Throat J. 2000 Sep. 79(9):704-9. [Medline].

  15. Tagra S, Talwar AK, Walia RL, Sidhu P. Waardenburg syndrome. Indian J Dermatol Venereol Leprol. 2006 Jul-Aug. 72(4):326. [Medline].

  16. Shim WK, Derieg M, Powell BR, Hsia YE. Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. J Pediatr Surg. 1999 Dec. 34(12):1853-5. [Medline].

  17. Moore SW, Johnson AG. Hirschsprung's disease: genetic and functional associations of Down's and Waardenburg syndromes. Semin Pediatr Surg. 1998 Aug. 7(3):156-61. [Medline].

  18. Verheij JB, Sival DA, van der Hoeven JH, et al. Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. Eur J Paediatr Neurol. 2006 Jan. 10(1):11-7. [Medline].

  19. Madden C, Halsted MJ, Hopkin RJ, Choo DI, Benton C, Greinwald JH Jr. Temporal bone abnormalities associated with hearing loss in Waardenburg syndrome. Laryngoscope. 2003 Nov. 113(11):2035-41. [Medline].

  20. Chang T, Hashimoto K, Bawle EV. Spontaneous contraction of leukodermic patches in Waardenburg syndrome. J Dermatol. 1993 Nov. 20(11):707-11. [Medline].

  21. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg's syndrome with facial palsy and lingua plicata: is that a new type of disease?. Cutis. 1999 Mar. 63(3):139-41. [Medline].

  22. Webb KM, Smith AJ, Dansby LM, Diskin CJ. Waardenburg syndrome with familial unilateral renal agenesis: a new syndrome variant?. Ther Apher Dial. 2015 Jun. 19(3):296-8. [Medline].

  23. Galasso C, Bombardieri R, Cerminara C, Stranci G, Curatolo P. Anophthalmia-Waardenburg syndrome with expanding phenotype: does neural crest play a role?. J Child Neurol. 2007 Nov. 22(11):1252-5. [Medline].

  24. Milunsky JM, Maher TA, Ito M, Milunsky A. The value of MLPA in Waardenburg syndrome. Genet Test. 2007 Summer. 11(2):179-82. [Medline].

  25. Broomfield SJ, Bruce IA, Henderson L, Ramsden RT, Green KM. Cochlear implantation in children with syndromic deafness. Int J Pediatr Otorhinolaryngol. 2013 Aug. 77 (8):1312-6. [Medline]. [Full Text].

Previous
Next
 
Marked facial asymmetry, lagophthalmos, a drooping right corner of the mouth. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.
Visage in profile demonstrates absence of nasofrontal angle, eyebrow hypertrichosis, upturned nasal tip, and shortened upper lip with a pronounced cupid's bow. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.
Brother and sister with Waardenburg syndrome. Image courtesy of Dourmishev LA et al, Cutis 1999; 63:139-40. Copyright 1999, Quadrant Healthcom, Inc.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.