We present the first two patients with the syndrome of meningomyelocele and severe Waardenburg syndrome type 3 (WS3) including telecanthus, characteristic facies, pigmentary abnormalities and upper extremity hypoplasia. Both patients possess small de novo interstitial deletions of chromosome 2 (2q35-36.2), the reported localization of PAX3. Deletion of PAX3 was confirmed by fluorescence in situ hybridization (FISH) and by hemizygousity of a PAX3 intragenic dinucleotide repeat polymorphism. Families of both patients showed autosomal dominant inheritance of minor neural crest anomalies, but not Waardenburg syndrome.

These patients represent examples of undiagnosed Waardenburg syndrome in the spina bifida population, offering a partial genetic explanation for these patients' neural tube defects. We address the possibility of a contiguous gene deletion syndrome or an interaction with another inherited neural crest syndrome as seen in these families. This analysis may lead to an explanation of the high incidence of spina bifida in Waardenburg syndrome pedigrees.

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