Klein-Waardenburg syndrome

Classification according to ICD-10
E70.3	Albinism
Q87.8	Other specified congenital malformation syndromes, not elsewhere classified
ICD-10 online (WHO version 2019)

The Klein – Waardenburg syndrome is a very rare congenital form of the Waardenburg syndrome with the main features of inner ear hearing loss , pigment anomalies , facial dysmorphism and additional malformation of the limbs .

Synonyms are: Waardenburg-Klein syndrome; van der Hoeve-Waardenburg-Klein syndrome; Waardenburg syndrome type III; Waardenburg syndrome type 3 (WS3); Klein Syndrome; Waardenburg syndrome with extremity abnormalities; english White forelock (poliosis) syndrome with multiple congenital malformations

The names refer to the author of the first description from 1947 and 1950 by the Geneva human geneticist and ophthalmologist David Klein (1908–1993) and from 1951 by Petrus Johannes Waardenburg .

A description by Jan van der Hoeve dates back to 1913 .

distribution

The frequency is given as 1–2 / 100,000, inheritance is autosomal dominant .

root cause

The disease are heterozygous or homozygous mutations in PAX3 - gene on chromosome 2 locus q36.1 basis.

Clinical manifestations

Clinical criteria are:

Skeletal malformations of the arm with hypoplasia , flexion contracture , fusion of carpal bones, syndactylia
sensorineural hearing loss to inner ear deafness
Pigmentation disorders of the iris ( iris heterochromia ), hair and skin, piebaldism
slight facial dysmorphism such as pseudo hypertelorism , laterally displaced inner corners of the eye and tear points (dystopia canthorum), hyperplasia of the eyebrows medially with synophrysis, including the bony parts of the nose, anomalies in the position of the jaw and teeth
Short stature
Brachycephaly
Clarity
Hair anomalies with deep frontal hairline

A lighter form is also known as "Mende syndrome". Homozygous forms are more affected than heterozygous forms.

diagnosis

The diagnosis is based on the clinical findings and can be confirmed by detecting the mutation.

therapy

So far, only symptomatic treatment is possible. The course is very different.

literature

M. Tekin, JN Bodurtha, WE Nance, A. Pandya: Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome? In: Clinical genetics. Volume 60, Number 4, October 2001, pp. 301-304, doi: 10.1034 / j.1399-0004.2001.600408.x , PMID 11683776 .
H. Piechowiak, C. Wasmer, FD Göbel: The Klein-Waardenburg syndrome. Report on three cases from a family with a literature review. In: Laryngology, Rhinology, Otology. Volume 64, Number 4, April 1985, pp. 194-197, PMID 4010406 .

Individual evidence

↑ ^a ^b Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
↑ ^a ^b ^c ^d Waardenburg syndrome type 3. In: Orphanet (database for rare diseases).
↑ D. Klein: Albinisme partiel (leucisme) accompagné de surdi-mutité, d'ostéo-myodysplasie, de raideurs articulaires congénitales multiples et d'autres malformations congénitales. In: Archive of the Julius Klaus Foundation for Heredity Research, Social Anthropology and Racial Hygiene. Volume 22, Number 3-4, 1947, pp. 336-342, PMID 18910900 .
↑ D. Klein: Albinisme partiel (leucisme) avec surdi-mutite, blepharophimosis et dysplasie myo-osteo-articulaire. In: Helvetica Paediatrica Acta Vol. 5, pp. 38-58, 1950.
^ Who named it David Klein
^ 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.
↑ J. Vam der Hoeve: Eye anomalies in congenital-familial deafness and in labyrinth disease. In. Clinical Monthly Ophthalmology Vol. 15, 1913, pp. 461–479
↑ Encyclopedia Dermatology
↑ Waardenburg syndrome, type 3. In: Online Mendelian Inheritance in Man . (English)
↑ CF Hoth, A. Milunsky, N. Lipsky, R. Sheffer, SK Clarren, CT Baldwin: Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I ( WS-I). In: American Journal of Human Genetics . Volume 52, Number 3, March 1993, pp. 455-462, PMID 8447316 , PMC 1682157 (free full text).

Web links

Rare Diseases

[Leiber-1] Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .

[Orpha-2] Waardenburg syndrome type 3. In: Orphanet (database for rare diseases).

[3] D. Klein: Albinisme partiel (leucisme) accompagné de surdi-mutité, d'ostéo-myodysplasie, de raideurs articulaires congénitales multiples et d'autres malformations congénitales. In: Archive of the Julius Klaus Foundation for Heredity Research, Social Anthropology and Racial Hygiene. Volume 22, Number 3-4, 1947, pp. 336-342, PMID 18910900 .

[4] D. Klein: Albinisme partiel (leucisme) avec surdi-mutite, blepharophimosis et dysplasie myo-osteo-articulaire. In: Helvetica Paediatrica Acta Vol. 5, pp. 38-58, 1950.

[5] Who named it David Klein

[6] 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.

[7] J. Vam der Hoeve: Eye anomalies in congenital-familial deafness and in labyrinth disease. In. Clinical Monthly Ophthalmology Vol. 15, 1913, pp. 461–479

[Altmeyer-8] Encyclopedia Dermatology

[9] Waardenburg syndrome, type 3. In: Online Mendelian Inheritance in Man . (English)

[10] CF Hoth, A. Milunsky, N. Lipsky, R. Sheffer, SK Clarren, CT Baldwin: Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I ( WS-I). In: American Journal of Human Genetics . Volume 52, Number 3, March 1993, pp. 455-462, PMID 8447316 , PMC 1682157 (free full text).