Patient with De Novo Mutation of Waardenburg Syndrome

Background: Waardenburg syndrome (WS) is an auditory-pigmentary syndrome caused by absence of melanocytes. Melanin contributes to skin, hair, and eye color and it plays an essential role in the normal function of the inner ear. Based on the phenotypic or genotypic characteristics, WS is clasificated in four types. The prevalence of WS is estimated to be 1/42,000 and it is responsible for 1% to 3% of cases of profound congenital deafness.

Objective: Describing a clinical case of WS type I with de novo mutation of PAX3 gene that associates other malformations that are not included in this syndrome.

Method: A 2 years old boy with WS type I who associates small ventricular septal defect, epispadias and congenital scoliosis with two hemivertebra. These two last defects are not described in WS clinical features. He has three mayor WS criteria (dystopia cantorum, congenital sensorineural hearing loss, white forelock) and two minor criteria (synofrys and broad and high nasal root with narrow nose), also bilateral blue iris. He has a profound bilateral hearing loss so he wears headphones with bilateral ventilation tubes pending of cochlear implant. Nowadays he is also pending of correction surgery of epispadias. Our patient has a healthy 5 years old brother and parents without WS features. The genetic study of parents was normal so his mutation has arisen de novo in heterozygosis c.667C>T (p.Arg222Ter) in PAX3 gene.

Conclusions: All patients with white forelock, hyperthelorism, iris heterocromia or distopia cantorum should be investigated for hearing loss. Patients with any malformation should be widely studied to rule out other associated malformations. The remarkable finding is that this patient associates abnormalities that we have not found associated with WS in the current literature.