Case of Waardenburg Shah syndrome in a family with review of literature

Abstract

Waardenburg syndrome is a rare disease characterized by sensorineural deafness in association with pigmentary defects. Depending on additional symptoms, WS have been classified into four types. Waardenburg syndrome type 4, also called as Waardenburg Shah Syndrome is a very rare congenital disorder with astounding variable clinical expression, characterized by pigmentary abnormalities of the hair (A white forelock of hair, premature graying) and pigmentary changes of the iris such as heterochromia or homochromia irides, sensorineural deafness and Hirschsprung disease. Three genes have been bestowed so far in consociation with EDNRB, EDN3, and SOX10 genes. The pattern of inheritance is multifarious with the SOX10 mutation affiliation with autosomal dominant inheritance whereas the EDNRB and EDN3 genes are passed down in an autosomally recessive pattern.

MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome

“…Type 3 shows abnormalities of arms and hands in addition to typical features of WS [ 7 ]. Type 4 presents symptoms of both WS and Hirschsprung disease, an intestinal disorder with severe constipation or blockage of the intestine [ 16 ]. In this study, the proband showed WS features with 1.75 W index which was less than 1.95 (The most significant difference between WS type 1 and type 2 is dystopia canthorum.…”

Waardenburg Syndrome Type-II in Twin Siblings: An Unusual Audio-Pigmentary Disorder

“…WS can be recognized by some specific clinical features that appear after birth; not all affected individuals possess all the clinical features [2]. It has four clinical subtypes based on the mutant gene and characteristic morphology [10]. These morphological features are broad nasal root, white forelock, the difference in the colour of eyes, congenital leukoderma, and sensorineural deafness [10].…”

“…It has four clinical subtypes based on the mutant gene and characteristic morphology [10]. These morphological features are broad nasal root, white forelock, the difference in the colour of eyes, congenital leukoderma, and sensorineural deafness [10]. It is a clinical diagnosis, and Waardenburg consortium proposed diagnostic criteria.…”

“…Our cases had four major criteria (white forelock, heterochromia, sensorineural hearing loss, first degree relative with WS), and one minor criterion to establish the diagnosis of WS-II. Most clinical features of WS-II except sensorineural deafness are benign in nature and do not need active intervention but severe deafness can be a serious problem [10]. An early diagnosis with social and vocational training and rehabilitation depending upon the extent of involvement remains the only rescue for these patients [5].…”

Frameshift variant in MITF gene in a large family with Waardenburg syndrome type II and a co-segregation of a C2orf74 variant

“…Genotype-phenotype correlation between a causative gene mutation and various clinical features in WS are largely unclear. Until recently, mutations in EDN3 (20q13.32), EDNRB (13q22.3), MITF (3p14p13), PAX3 (2q36.1), SNAI2 (8q11.21), and SOX10 (22q13.1) have been reported in isolated patients as well as in families segregating WS [6][7][8]. For an instance, mutations of PAX3 gene is recognized as a key indicator for the clinical features of WS1 and WS3, and mutations in MITF, SOX10, and SNAI2 genes are identified in WS2.…”