Waardenburg syndrome

Don’t it make my blue eyes brown: heterochromia and other abnormalities of the iris

“…38,40 The results of this study were published in a seminal paper in the American Journal of Human Genetics in 1951 41 and define the syndrome now known as Waardenburg syndrome type-I, which had six main features: lateral displacement of the medial canthi combined with dystopia of the lacrimal punctum and blepharophimosis; prominent broad nasal root; hypertrichosis of the medial part of the eyebrows, white Eye forelock, heterochromia iridis; and deaf-mutism. 40,41 There are now four recognised variants of Waardenburg syndrome (types I-IV) all of which are inherited by an autosomal dominant trait, with the exception of Waardenburg syndrome type-IV, which appears to have a mostly autosomal recessive mode of inheritance. 38 Mutations of the PAX3 gene have been implicated in Waardenburg syndrome types I and III, whereas approximately 15% of type-II have mutations of the MITF gene.…”

“…38 Mutations of the PAX3 gene have been implicated in Waardenburg syndrome types I and III, whereas approximately 15% of type-II have mutations of the MITF gene. 40 Mutations of the endothelin-3 (EDN3), endothelin receptor-B (EDNRB), and SOX10 genes have been found in patients with Waardenburg syndrome type-IV. 40,42 PAX3, MITF, and SOX10 are transcription factors and EDNRB and EDN3 are signalling molecules, all of which appear to have a role in the development of melanocytes from primitive neural crest cells.…”

“…40 Mutations of the endothelin-3 (EDN3), endothelin receptor-B (EDNRB), and SOX10 genes have been found in patients with Waardenburg syndrome type-IV. 40,42 PAX3, MITF, and SOX10 are transcription factors and EDNRB and EDN3 are signalling molecules, all of which appear to have a role in the development of melanocytes from primitive neural crest cells. 43,44 Three types of pigmentary disturbance of the iris have been observed in Waardenburg syndrome and include complete heterochromia iridis, partial, or segmental heterochromia (Figure 1a), which maybe unilateral or bilateral, and bilateral isohypochromia iridis (pale blue eyes).…”

“…43,44 Three types of pigmentary disturbance of the iris have been observed in Waardenburg syndrome and include complete heterochromia iridis, partial, or segmental heterochromia (Figure 1a), which maybe unilateral or bilateral, and bilateral isohypochromia iridis (pale blue eyes). 38,40 Iris heterochromia, either partial or complete, is found in between 21 and 28% of individuals with Waardenburg syndrome 40 and appears to be most common in the type-II variant, with a reported frequency of 47%. 45 Isohypochromia iridis has a reported incidence of 14.9-42%.…”

“…45 Isohypochromia iridis has a reported incidence of 14.9-42%. 40 Histopathological studies of the irides of patients with Waardenburg syndrome are limited. Mullaney et al 46 described the light and electron microscopic findings of the irides in a patient with the type-II variant of Waardenburg syndrome.…”