Clinical characteristics: Waardenburg syndrome type I (WS1) is an auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin along with dystopia canthorum (lateral displacement of the inner canthi). The hearing loss in WS1, observed in approximately 60% of affected individuals, is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. Most commonly, hearing loss in WS1 is bilateral and profound (>100 dB). The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs.
Diagnosis/testing: The diagnosis of WS1 is established in most individuals by physical examination for clinical criteria including: sensorineural hearing loss, pigmentary changes in the hair and eyes, dystopia canthorum identified by calculation of the W index, and specific facial features. Identification of a heterozygous PAX3 pathogenic variant by molecular genetic testing establishes the diagnosis if clinical features are inconclusive.
Management: Treatment of manifestations: Management of the hearing loss depends on its severity; cochlear implantation has been successfully used in individuals with WS1.
Evaluation of relatives at risk: If the family-specific PAX3 pathogenic variant is known, molecular genetic testing of relatives at risk allows for early screening of those at risk for hearing loss.
Pregnancy management: Folic acid supplementation in pregnancy is recommended for women at increased risk of having a child with WS1 because of the possibly increased risk for neural tube defects associated with WS1.
Genetic counseling: Waardenburg syndrome type I (WS1) is inherited in an autosomal dominant manner. The majority of probands have an affected parent. A minority of probands do not have an affected parent and are presumed to have WS1 as a result of a de novo pathogenic variant. Offspring of an individual with WS1 have a 50% chance of inheriting the pathogenic variant. If the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk may be available from a clinical laboratory that offers either testing for this disease/gene or custom prenatal testing. Although this testing can determine whether the fetus has inherited the PAX3 pathogenic variant, it cannot determine the clinical manifestations or their severity.
Copyright © 1993-2023, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.