Dermatology Online Journal
- Author(s): Sankar, Rajesh
- et al.
Shah-Waardenburg syndromeDermatology Consultation, Kalamassery, Ernakulam, India
Dermatology Online Journal 14 (1): 19
A case of Shah-Waardenburg syndrome, a rare variant of Waardenburg syndrome, is presented. Inherited as an autosomal recessive or dominant trait, the disorder presumably results from defective migration of neural crest cells. It clinically manifests with pigmentary anomalies and congenital megacolon.
A 14-month-old boy was brought in with a complaint of white hair on the anterior scalp since birth. Some 2 months prior to presentation he had required resection and anastomosis of the large bowel following intestinal obstruction associated with congenital megacolon. Auditory-evoked responses done during neonatal screening for deafness had not shown any abnormality. On examination, the child had a white forelock arising out of normally pigmented skin. He had a broad nasal root, lateral displacement of the medial canthi, and blue colored irides. A scar resulting from the surgery and the subsequent colostomy was visible over the left upper and middle quadrant of the abdomen.
His father was also born with a white forelock; during his childhood this had turned to normal dark brown hair. He was also operated upon at the age of 2 years for an intestinal obstruction, presumably resulting from congenital megacolon.
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Shah-Waardenburg syndrome is an unusual variant of Waardenburg syndrome that is associated with white forelock, white eyebrows and eyelashes, heterochromic irides, and intestinal obstruction associated with a long-segment Hirschprung disease.
Petrus Johannes Waardenburg initially described the syndrome , which came to be labeled with his name in 1951, citing the following main features:
- White forelock
- Broad nasal root
- Lateral displacement of the medial canthi
- Hypertrichosis of medial part of eyebrows
- Heterochromia irides
- Deaf mutism
In 1981 Krishnakumar N. Shah described the variant of the syndrome exhibited by this case, the association of Waardenburg syndrome with long segment Hirschsprung’s disease . Also known as Waardenburg syndrome type 4, Shah-Waardenburg syndrome is rare but not exceptional, having more than 50 published cases. The disease is inherited either as an autosomal recessive trait, from mutations of endothelin-B receptor (EDNRB) or endothelin-3 (EDN3) genes, or as an autosomal dominant trait when related to SOX10 gene mutations [3, 4]. The other variants of Waardenburg syndrome are autosomal dominant in inheritance. Defective migration of the neural crest cells (i.e., the melanocytes and the neuroblasts contributing the enteric ganglion cells) has been postulated as a cause of this disorder .
Pigmentary abnormalities affecting the skin, hair and the eyes are the hallmark of Waardenburg syndrome [1, 6]. Cutaneous lesions include achromic patches as seen in piebaldism, and occasionally, hyperpigmented macules on normal-looking skin. White forelock or poliosis affecting the anterior scalp may be present at birth, but also may appear later. The poliosis may persist throughout life or may spontaneously become pigmented later . Premature graying also has been reported in patients with Waardenburg syndrome.
Histopathologic examination of the achromic skin shows absent to very few DOPA-positive cells. Melanocytes containing melanosomes surrounded by a clear halo, are seen at the edges of the lesion. Lack of melanocytes in the hair matrix leads to their absence in the cortex, cuticle, and inner root sheath of the hair, resulting in the white forelock.
Pigmentary anomalies affecting the eyes include heterochromic irides (different colored irides), bilateral hypochromic irides (pale blue irides), and pigmentary alterations in the fundus. Other eye abnormalities include dystopia canthorum (wherein the medial canthi are laterally displaced), and synophrys or medial eyebrow flare, with a broad nasal root.
Bowel involvement in Shah-Waardenburg syndrome is characteristic; there is absence of the myenteric (Auerbach) plexus and the submucous (Meissner) plexus with hyperganglionosis and ectopic ganglia in the lamina propria of the long segment . This leads to chronic constipation, intestinal obstruction, and failure to thrive, which usually begins during the time of weaning.
Sensorineural deafness can be present in 50 percent of the cases, presenting at birth or later in life, but mental deficiency is not seen.
The clinical picture of this syndrome is very typical. Treatment requires surgical intervention for the Hirschsprung disease. Proper audiological assessment at birth and at periodic intervals can detect hearing impairment. Only a few patients, ascribed to specific SOX10 mutations, have additional neurological impairment. The white forelock can regress or persist throughout life. Genetic counseling must be provided for families with this disorder, and the occurrence rate depends on the specific molecular etiology.
References1. Waardenburg PJ: A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 1951; 3: 195-253. PubMed
2. K. N. Shah, et al: White forelock, pigmentary disorder of irides, and long segment Hirschprung disease: Possible variant of Waardenburg syndrome. Journal of Pediatrics, St. Louis 1981, 99: 432-435. PubMed
3. P. Edery, T. Attié, Jet al: Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome). Nature Genetics 1996, 12: 442-444. PubMed
4. R. M. W. Hofstra, J. Osinga, et al: A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Nature Genetics 1996; 12: 445-447. PubMed
5. Paige Kaplan, et al: Piebaldism-Waardenburg syndrome: Histopathologic evidence for a neural crest syndrome. American Journal of Medical Genetics 1988; 31: 679-688. PubMed
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8. Shim WK, Derieg M, Powell BR, Hsia YE: Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. J Pediatr Surg 1999; 34: 1853-5. PubMed
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