1. Waardenburg Shah Syndrome: A Case Report
Ngu L, Wong AC, Chan LG
Department of Paediatrics
Sarawak General Hospital
Introduction
Waardenburg Syndrome (WS) is a rare disease with an incidence of 1 in 50,000 live births. It is characterized by congenital hearing loss and changes in pigmentation of the hair, skin and eyes. There are 4 known types of Waardenburg syndrome and they are distinguished by their physical characteristics and genetic cause. Waardenburg Syndrome type IV (WS4) also known as Waardenburg-Shah Syndrome presents with an additional feature of Hirschsprung’s disease. This is an even rarer condition with less 100 cases reported. We will like to highlight the importance to consider the diagnosis of WS4 in an infant with WS and feeding intolerance.
Case Report
Infant S was the first child of a single teenage mother with an uneventful antenatal history. He was born term at 38 weeks gestation via caesarean section for breech presentation. He was unexpectedly depressed at birth with poor apgar score requiring intubation and assisted ventilation. Examination revealed an infant with generalized hypotonia, bilateral congenital talipes equinovarus, undescended left testis, skin hypopigmentation, white forelock (Fig 1) and bilateral bright blue iris (Fig 2) which was suggestive of Waardenburg Syndrome. He did not tolerate early tube feeding and had abdominal distension. Abdominal radiograph showed dilated small bowel with absence of rectal gas. A contrast enema was thereafter done which showed diffuse microcolon with an impression of total aganglionic colon (Fig 3).
He was subsequently transferred to a tertiary centre with paediatric surgery services. A laparotomy performed at D3 of life found dilated small bowel with microcolon and a transition zone 40cm proximal to the ileo-caecal junction. An ileostomy was created. Biopsy of the distal ileostomy site and rectal biopsy revealed aganglionic bowel and therefore confirming the diagnosis of Hirschprung’s disease. He was therefore diagnosed as Waardenburg-Shah Syndrome.
There was problem with initiating feeding with initial non-functioning ileostomy. Feeding was started slowly at day 13 of life with gradual increment and only reaching full feed at day 25 of life. There was subsequently increasing ieostomy losses with feeding resulting in episodes of dehydration and electrolyte imbalances requiring fluid replacement and electrolytes correction. The ileostomy losses reduced when substituting expressed breast milk with extensively hydrolysed formula but he remained to have poor weight gain requiring continued supplemental parenteral nutrition.
He also required prolonged ventilation due to central hypoventilation and was only manage to be extubated to nasal CPAP at D16 of life. Magnetic resonance imaging (MRI) of the brain showed absence of normal T1 hyperintensities at posterior limb of internal capsules; with mild increase in T2 signal intensities involving the white matter at the region posterior and superior to the trigone bilaterally. Features suggest delayed myelination or hypomyelination. A bedside OAE hearing assessment was performed with no signal detected from both ears. Brainstem auditory evoke response (BAER) was scheduled but ultimately unable to be done.
The mother was counseled regarding the overall poor prognosis and decided for conservative management in the event of acute deterioration. The infant eventually died in the NICU due to nosocomial infection at day 84 of life.
Discussion
Diagnostic criteria for Waardenburg syndrome (WS) proposed by the Waardenburg Consortium consist of five major criteria and five minor criteria. Major criteria consist of congenital sensorineural hearing loss, white forelock, hair hypopigmentation, pigmentation abnormality of the iris, dystopia canthorum and affected first degree relative. Minor criteria includes skin hypopigmentation, synophrys, broad/high nasal root, hypoplastic alae nasi and premature graying of the hair. The clinical diagnosis of WS requires at least 2 major criteria or one major and one minor criteria. There was no family history of WS in this case but he fulfilled the clinical features of WS.
Waardenburg Syndrome type IV (WS4), also known as Waardenburg-Shah syndrome, is an audiotory-pigmentary synbdrome characterized by pigmentary abnormalities of the hair, skin and eyes, congenital hearing loss, and Hirschprung’s disease. A laparotomy is usually necessary for small intestinal biopsy to identify level of anganglionosis. The length of the anganglionic segment involved affects the prognosis of the disease. A long segment involvement as in this case carries a poor overall prognosis for the gut.
WS Type IV is an autosomal recessive condition. Several gene alterations have been described in the development of WS Type IV such as endothelin EDN, EDNRB and SOX 10 genes. SOX10 mutation has also been reported to be associated with a unique phenotype of Type IV WS accompanied by peripheral neuropathy and central demyelination which is also described in this case. The genetic study is not available in Malaysia.
Postoperative complications in type IV WS are similar to those seen in short bowel syndromes. These includes fluid electrolyte imbalance, bacterial overgrowth, and TPN and catheter related complications. The mortality is directly related to sepsis and hepatic failure.
Reference
Read and Newton, 1997 and Pingault et al., 2010
Branski D, Denis NR, Neale JM, et al. Hirschsprung's disease and Waardenburg's syndrome. Pediatrics. 1979;63:803–805
K Inoue, K Shilo, et al. Congenital hypomylinatins neuropathy, central dysmyelination and Waardenburg-Hrischprung disease : phenotypes linked by SOX10 mutation. Annal of neurology (6):
A Mahmoudi, M Rami, et al. Shah-Waardenburg Syndrome. Pan Afr Med J.2013;14:60
Fig 1: White forelock
Fig 2: Bilateral blue iris
Fig 3:
Diffuse microcolon on contrast enema