Waardenburg syndrome iv E70.32

WS4 is the association of Waardenburg syndrome with Hirschsprung's disease

See under Waardenburg syndrome IV

By 2002, only 48 cases had been described in the English literature. The coexistence of WS and Hirschsprung's disease (HD) is quite rare. The incidence of WS is 2/100,000 and of HD 2/10,000, so the probability of the two diseases occurring together is 4 in 1 million, based on the known number of cases. The incidence of congenital deafness is 1/1000, and a coincidental co-occurrence with HD would be expected at a rate of 1 in 5 million

Several gene mutations have been described that play a special role in the development of SWS, such as the genes for endothelins(EDN), EDNRB and SOX10. A SOX10 mutation is now considered an important cause of neurocristopathies including SWS (Chan KK et al. 2003). Other associated gene mutations, such as those of the EDN3 and EDNRB genes, may indicate that disrupted EDN signaling pathways are partly responsible for these syndromes.

There are five main and five secondary criteria for the diagnosis of Waardenburg syndrome. The major criteria include sensorineural hearing loss, a pigmentary disorder of the iris (two different colored eyes or iris bicolor or a characteristic bright blue iris), hypopigmentation of the hair (white forelock or white hair on other parts of the body), dystopia canthorum (lateral displacement of the inner canthi), and a first-degree relative who has already been diagnosed with Waardenburg syndrome.

Less significant criteria include hypopigmentation of the skin (congenital white skin patches), medial eyebrow rash (synophrys), broad nasal root, hypoplasia alae nasi and poliosis.

The clinical diagnosis of WS requires at least 2 major criteria or one major and one minor criterion. The diagnosis of HD in type IV WS patients is made on the basis of history, physical examination, plain abdominal radiograph, barium enema, anorectal manometry, and rectal biopsy. A barium enema is often not diagnostic in young children with extensive aganglionosis, so a laparotomy is required to obtain small bowel biopsy samples to determine the extent of the aganglionosis. The biopsy samples taken from the entire intestinal wall during the operation and the examination of the appendix sample enabled a clear diagnosis to be made and the length of the aganglion segment to be determined.

The length of the affected aganglionic segment influences the clinical course of the disease and is also very important for planning surgical treatment.

1. Ariturk E et al. (1992) A case ofWaardenburg syndrome and aganglionosis. Turk J Pediatr. 34:111-114.
2. Chan KK et al. (2003) Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: differential effects on target gene regulation. J Cell Biochem 3:573-85.
3. Currie ABM et al. (1986) Associated developmental abnormalities of the anterior end of the neural crest: Hirschsprung's disease-Waardenburg's syndrome. J Pediatr Surg 21:248-250.
4. Mahmoudi A et al (2013) Shah-Waardenburg syndrome. Pan Afr Med J 14:60.
5. Toki F et al. (2003) Intestinal aganglionosis associated with theWaardenburg syndrome: report of two cases and review of the literature. Pediatr Surg Int 19:725.
6. Verheij JB et al. (2006) Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. Eur J Paediatr Neuro 1:11-17.