Waardenburg syndrome

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Classification according to ICD-10
Q87.8 Other specified congenital malformation syndromes, not elsewhere classified
ICD-10 online (WHO version 2019)

The Waardenburg syndrome is a congenital, hereditary disease caused by a variable combination of pigmentation disorders of the eyes, the skin and the hair, by hearing loss and malformations of the face ( facial dysmorphism is marked).

Four different forms of Waardenburg syndrome can be distinguished. Except for type IV, the disease is predominantly inherited as an autosomal dominant trait.

Epidemiology

The frequency of Waardenburg syndrome is given as 1: 4500 new cases per year ( incidence ). The Waardenburg syndromes make up about 2% percent of cases of congenital hearing loss.

Forms and causes

According to genetic and clinical criteria, four main types of Waardenburg syndrome (WS) are distinguished (WS1-WS4). The four types can in turn be divided into sub-forms:

Types of Waardenburg Syndrome
Type Synonyms and variants Locus (s)
Type I. WS1 2q35
Type II WSII
WS2A
WS2B
WS2C
WS2D 		3p14.1-p12.3
1p21-p13.3
8p23
8q11
Type III Klein-Waardenburg syndrome
WS3 		2q35
Type IV Waardenburg-Shah-Syndrome
Waardenburg-Hirschsprung-Syndrome
WS4 		13q22, 22q13, 20q13.2-q13.3

The Waardenburg syndromes WS1, WS2 and WS3 are inherited in an autosomal dominant manner; only autosomal recessive inheritance patterns have been demonstrated for WS4.

WS1 and WS3 are caused by mutations in the Pax3 gene. The gene codes, among other things, for a 479 amino acid protein that is involved in the regulation of the transcription factor MITF ( microphthalmia-associated transcription factor ). MITF is involved in the regulation of melanocyte development, which is disturbed in all known Waardenburg syndromes.

The WSIIA is caused by a mutation directly in the MITF gene. In the WSIIB, only the DNA locus is known (WSIIB: 1p21-p13.3, WSIIC) in which mutations occur. The WSIIC is caused by a balanced translocation from chromosome 4 to 8. This means that a section of DNA that is normally found on chromosome 4 is located on chromosome 8 in WSIIC. The very rare WSIID has a mutation in the so-called SNAI2 gene. This is also a transcription factor that is expressed in the naural crest cells during embryonic development. The WSIIE is based on a gene mutation in the SOX10 gene.

In contrast to Waardenburg syndromes 1–3, WS4 is inherited as an autosomal recessive trait. So far, mutations in the endothelin- 3 and endothelin-B receptor genes and the SOX10 gene have been detected.

Clinical picture

Eyelids that have grown together on the nasal side (ankyloblepharon) in Waardenburg-Klein syndrome

The deafness in Waardenburg syndrome is due to defects in the development of tissue in the original neural crest. The disruption of pigment cells, which are also derived from neuronal tissue, mainly affects the iris , eyebrows, and sometimes also the skin and scalp hair, which leads to hypopigmentation . A different coloration of the eyes ( iris heterochromia ) is particularly noticeable , i. H. Affected can z. B. have one blue and one brown eye. Dysplasia in the form of misaligned eyes and malformations of the bony skull are also part of Waardenburg syndrome. This appears in part as a shift in the crease of the eyelid or a lateral shift in the inner corner of both eyes ( Dystopia Canthorum ).

history

Waardenburg syndrome was first described in 1951 by the Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg (1886–1979).

Trivia

  • The investigating FBI agent Deacon Novak and his family from the novel 'Thorn Girl' by Karen Rose have Waardenburg syndrome.
  • In the Münster crime scene episode Hinkebein , the discovery of Waardenburg syndrome (in this case characterized by different colored eyes) both in the daughter of the dead and in the daughter's father, who was not known until then, provides a decisive clue for the conviction of the father as a murderer .
  • The 21st episode "The Signs In The Silence" of the sixth season of the US crime series Bones is about a child who was initially suspected of murder and was born with Waardenburg syndrome. Psychological aspects of dealing with the disease are also dealt with.

Individual evidence

  1. ^ Waardenburg syndrome. (No longer available online.) Orphanet.net , formerly in the original ; Retrieved February 27, 2009 .  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.orphanet.net  
  2. ↑ a b J. Wendler, W. Seidner, U. Eysholdt: Textbook of Phoniatry and Pedaudiology . 4th edition. Thieme-Verlag, 2005, ISBN 3-13-102294-9 , p. 61, (online)
  3. ↑ AL Dourmishev et al.: Waardenburg syndrome. In: International Journal of Dermatology . 1999; 38 (9), pp. 656-663. PMID 10517681
  4. ↑ WAARDENBURG SYNDROME, TYPE I.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ WAARDENBURG SYNDROME, TYPE IIA.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ WAARDENBURG SYNDROME, TYPE IIB.  In: Online Mendelian Inheritance in Man . (English)
  7. ↑ WAARDENBURG SYNDROME, TYPE IIC.  In: Online Mendelian Inheritance in Man . (English)
  8. ↑ WAARDENBURG SYNDROME, TYPE IID.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ WAARDENBURG SYNDROME, TYPE III.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ WAARDENBURG SYNDROME, TYPE IV.  In: Online Mendelian Inheritance in Man . (English)
  11. ^ PJ Waardenburg: A new syndrome combining developmental anomalies of the eyelids, eyebrowns, and nose root with pigmentary defects of the iris and head hear with congenital deafness. In: American Journal of Human Genetics. (1951) 3, pp. 195-253.
  12. ↑ Karen Rose: Thorn Girl . 1st edition. Knaur, Munich 2015, ISBN 978-3-426-65361-6 (Original title: Closer than you think . Translated by Kerstin Winter).
  13. ↑ WORLD: Waardenburg Syndrome: Why the "crime scene" girl had two eye colors . In: THE WORLD . March 12, 2012 ( welt.de [accessed September 11, 2018]).
  14. ↑ https://www.fernsehserien.de/bones-die-knochenjaegerin/haben/6x21-das-schweigende-laemmchen-249961

supporting documents

  • A. Karaman, C. Aliagaoglu: Waardenburg syndrome type 1 . In: Dermacol Online Journal. (2006) 30; 12 (3), p. 21. (case description with images)
  • F. Mouriaux, M. Hamedani, T. Hurbli and others: Waardenburg's syndrome . In: J Fr Ophtalmol. (1999) 22 (7), pp. 799-809. (pdf) French article with a detailed description and pictures