Piebaldism‐Waardenburg syndrome: Histopathologic evidence for a neural crest syndrome

Abstract

Piebaldism, an autosomal dominant trait, is characterized by patchy hypopigmentation of the face, anterior chest, abdomen, and limbs, heterochromia/bicolored irises, congenital megacolon, and deafness. A 4-month-old Inuit (Eskimo) boy with these manifestations also had left pulmonic artery stenosis, ocular ptosis, and unilateral duplication of the renal collecting system. Evidence is presented for both qualitative and quantitative derangement of neural crest derivatives in this syndrome. Histologically, hypoganglionosis, hyperganglionosis, and ectopic ganglia in lamina propria (neuronal colonic dysplasia [NCD]) were documented in the rectum. The appendix, proximal to the clinical transition zone, showed similar dysplasia. In the hypopigmented skin, multiple microscopic sections were devoid of melanocytes, with no melanin in adjacent basal cells. The hyperpigmented skin contained melanin throughout the basal layer, but the melanocytes were unevenly distributed. Most tissues affected in this boy are of neural crest origin; pathogenesis could be due to faulty migration along the established pathways involving either the borders (basal laminae) or the components of the extracellular matrix (fibronectin, cytotactin, laminin, glycosaminoglycans, and collagen). The similarities between piebaldism and the Waardenburg syndromes are discussed.

Hirschsprung disease, associated syndromes, and genetics: a review

“…A SOX10 mutation has been reported in one of these families60; (2) Black locks-Albinism-Deafness Syndrome (BADS, MIM 227010) with TCA-HSCR reported in one case61; (3) aganglionic megacolon associated with familial piebaldism (MIM 172800)62 63; (4) HSCR and profound congenital deafness but with no other WS features has also been reported 64…”

Hirschsprung disease, associated syndromes and genetics: a review

“…Related syndromes associating pigmentary anomalies and HSCR include: (1) Yemenite deaf-blind hypopigmentation syndrome (MIM 601706), a SOX10 mutation having been reported in one of these families153; (2) Black Locks-Albinism-Deafness syndrome (BADS, MIM 227010) with TCA-HSCR in one case169; (3) aganglionic megacolon associated with familial piebaldism (MIM 172800)170 171; (4) HSCR and profound congenital deafness but with no other WS features has also been reported 229…”

Waardenburg syndrome associated with bilateral renal anomaly

“…Management of the patient depends on the characteristics of the renal anomaly as presented previously and in our case. Duplicated collecting system such as in the first reported case [2] does not require treatment if it is not associated with another anomaly as vesico-ureteral reflux or UPJ obstruction. Nephrectomy was the choice of treatment of multicystic dysplastic kidney in the second report [3] and right nephrectomy was performed in the present case because it did not show any function in mercaptoacetyltriglycine dynamic scintigraphy and had a dimercaptosuccinic acid technetium Tc 99m uptake of 4%.…”

“…The association of Waardenburg syndrome and renal anomaly is extremely rare and was reported only in a newborn and in an infant [2,3]. The third case of Waardenburg syndrome type I with renal anomalies is presented here, with special emphasis on diagnosis and prognosis.…”