Waardenburg syndrome

The estimated prevalence is 1/20,000-1/40,000 in the general population. Waardenburg syndrome is identified in approximately 3% of individuals with congenital deafness.

Waardenburg syndrome is inherited in an autosomal dominantor recessive manner, depending on the gene involved. In case of autosomal dominant inheritance, each child of an affected individual has a 50% chance of inheriting the pathogenic variant. In case of autosomal recessive inheritance, both parents of an affected individual are typically heterozygous carriers; the recurrence risk for siblings is 25% in each pregnancy. Carrier testing of at-risk relatives requires prior identification of the familial pathogenic variants. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

The clinical diagnosis of Waardenburg syndrome is established by the Waardenburg Consortium criteria (1992), which require two major criteria or one major plus two minor criteria. Meeting these criteria constitutes the clinical diagnosis.

Main differential diagnoses include:

• Piebaldism: white forelock and patchy congenital hypopigmentation with hyperpigmented borders; dystopia canthorum is absent and sensorineural deafness is only rarely described; KIT, SNAI2
• Tietz syndrome: generalised hypopigmentation with profound congenital sensorineural deafness, distinguished from the patchy depigmentation of Waardenburg syndrome; MITF

• Establishing the diagnosis: molecular genetic testing identifies the underlying pathogenic variant and confirms the clinical diagnosis at the molecular level.
• Specific and individualised clinical management: identification of the causative gene and variant informs management decisions and supportive care, which are decided by the treating physicians in consultation with the affected individual, and is a prerequisite for targeted medical care.
• Family member testing: once the familial pathogenic variant is known, predictive testing can be offered to at-risk relatives, supporting genetic counselling and informed reproductive decision-making.

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• Li W, Mei L, Chen H, Cai X, Liu Y, Men M, et al. New genotypes and phenotypes in patients with 3 subtypes of Waardenburg syndrome identified by diagnostic next-generation sequencing. Neural Plast. 2019;2019:7143458. doi:10.1155/2019/7143458. PMID:; PMCID: PMC6415303.
• 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(4):391-406. doi:10.1002/humu.21211. PMID:.
• Farrer LA, Grundfast KM, Amos J, Arnos KS, Asher JH Jr, Beighton P, et al. Waardenburg syndrome type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet. 1992;50(5):902-13. PMID:; PMCID: PMC1682585.