Waardenburg syndrome with extended aganglionosis: report of 3 new cases

Karaca, İrfan; Türk, Emin; Ortaç, Ragıp; Kandirici, Aliye

doi:10.1016/j.jpedsurg.2009.02.057

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…The extent of the intestinal aganglionosis and the phenotypic manifestations are variable, and could lead to severe occlusion in neonates [Karaca et al, 2009]. A few patients present with an intestinal phenotype not related to HD (chronic intestinal pseudoobstruction: obstruction without an identified cause or obstacle) [Valenzuela et al, 1995].…”

Section: Clinical Features and Classificationmentioning

confidence: 99%

Review and update of mutations causing Waardenburg syndrome

et al. 2010

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Waardenburg syndrome (WS) is characterized by the association of pigmentation abnormalities, including depigmented patches of the skin and hair, vivid blue eyes or heterochromia irides, and sensorineural hearing loss. However, other features such as dystopia canthorum, musculoskeletal abnormalities of the limbs, Hirschsprung disease, or neurological defects are found in subsets of patients and used for the clinical classification of WS. Six genes are involved in this syndrome: PAX3 (encoding the paired box 3 transcription factor), MITF (microphthalmia-associated transcription factor), EDN3 (endothelin 3), EDNRB (endothelin receptor type B), SOX10 (encoding the Sry bOX10 transcription factor), and SNAI2 (snail homolog 2), with different frequencies. In this review we provide an update on all WS genes and set up mutation databases, summarize molecular and functional data available for each of them, and discuss the applications in diagnostics and genetic counseling.

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Section: Clinical Features and Classificationmentioning

confidence: 99%

Review and update of mutations causing Waardenburg syndrome

et al. 2010

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“…WS4 is rare, with an incidence of ∼1/40,000–1/50,000 live-births, and occurs in all races. To the best of our knowledge, there are only 74 WS4 cases described (2012) in the English literature [2], [3], [4], [5], [6], [7], [8]. WS4 can occur sporadically or it segregates in families in an autosomal dominant or recessive inheritance pattern with reduced penetrance [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia

et al. 2013

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We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4). WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs) using Illumina-HumanOmni2.5-Beadchip and for coding sequence mutations in WS4 genes (EDN3, EDNRB, or SOX10) and in the main HSCR gene (RET). Confocal microscopy and immunoblotting were used to assess the functional impact of the mutations. A heterozygous A/G transition in EDNRB was identified in 4 affected and 3 unaffected individuals. While in EDNRB isoforms 1 and 2 (cellular receptor) the transition results in the abolishment of translation initiation (M1V), in isoform 3 (only in the cytosol) the replacement occurs at Met91 (M91V) and is predicted benign. Another heterozygous transition (c.-248G/A; -predicted to affect translation efficiency-) in the 5′-untranslated region of EDN3 (EDNRB ligand) was detected in all affected individuals but not in healthy carriers of the EDNRB mutation. Also, a de novo CNVs encompassing DACH1 was identified in the patient with heterochromia iridum and HSCRSince the EDNRB and EDN3 variants only coexist in affected individuals, HSCR could be due to the joint effect of mutations in genes of the same pathway. Iris heterochromia could be due to an independent genetic event and would account for the additional phenotype within the family.

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“…Although the length of the involved intestinal segment varies in this syndrome, most patients have total colonic aganglionosis with or without small-bowel involvement [2,7]. The baby had total colonic aganglionosis with extended small-bowel involvement (ileum).…”

Section: Discussionmentioning

confidence: 99%