Waardenburg Syndrome

Abstract

A 58-year-old woman with asthma presented to our hospital after 5 days of coughing and worsening dyspnea. Besides wheezing and mild respiratory distress, physical examination revealed complete heterochromia (a right brown eye and a vivid blue left eye) and dystopia canthorum (lateral displacement of inner canthus of the eyes) (Figure). She had had different colored eyes since birth and has been dyeing her hair since she was 18, because it had become entirely white. The first-born of her three sons had blue eyes and the second one had congenital deafness, white hair, and a blue eye. Her youngest son and her husband did not have any apparent abnormality. The patient told us her deaf son had received a diagnosis of Waardenburg syndrome within his first year of life. She was discharged with no symptoms. Waardenburg syndrome is a group of genetic conditions that can produce sensorineural hearing loss, changes in pigmentation of the hair, skin, and eyes, craniofacial alterations, musculoskeletal limb abnormalities, and Hirschsprung disease.1Pingault V. Ente D. Dastot-Le Moal F. et al.Review and update of mutations causing Waardenburg syndrome.Hum Mutat. 2010; 31: 391-406Crossref PubMed Scopus (422) Google Scholar, 2Ur Rehman H. Heterochromia.CMAJ. 2008; 179: 447-448Crossref PubMed Scopus (8) Google Scholar It accounts for 1% to 3% of all cases of congenital deafness and is usually inherited in an autosomal dominant pattern.1Pingault V. Ente D. Dastot-Le Moal F. et al.Review and update of mutations causing Waardenburg syndrome.Hum Mutat. 2010; 31: 391-406Crossref PubMed Scopus (422) Google Scholar The features of Waardenburg syndrome differ among patients, even among people in the same family, as happened in our case. Mutations in any of the 6 genes involved in this entity disrupt the normal development of melanocytes, leading to atypical pigmentation and various degrees of hearing loss. Although most instances of iris heterochromia are sporadic and have no associated underlying abnormalities,2Ur Rehman H. Heterochromia.CMAJ. 2008; 179: 447-448Crossref PubMed Scopus (8) Google Scholar the present case is a reminder that congenital heterochromia can also occur. In this regard, physical examination plays a conspicuous role in diagnosing Waardenburg syndrome and other inborn pigmentary disorders.