RESUMEN
We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy-Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis.
Asunto(s)
Trastornos de los Cromosomas/genética , Síndrome de Dandy-Walker/genética , Holoprosencefalia/genética , Encéfalo/patología , Deleción Cromosómica , Trastornos de los Cromosomas/complicaciones , Trastornos de los Cromosomas/patología , Cromosomas Humanos Par 13/genética , Proteínas de Unión al ADN , Síndrome de Dandy-Walker/complicaciones , Síndrome de Dandy-Walker/patología , Femenino , Eliminación de Gen , Holoprosencefalia/complicaciones , Holoprosencefalia/patología , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
The authors report two cases of the rare concurrence of intestinal aganglionosis and Waardenburg syndrome in Japanese infants. The patients were a 1-month-old girl and a 3-month-old boy at diagnosis, and both of them had either short segment or ultra-short segment aganglionosis. A review of 48 cases in the literature showed that the extent of the aganglionic segment is quite variable, from nearly total to ultra-short. The clinical features of aganglionosis in Waardenburg syndrome would appear to bear similarity in sex ratio and the extent of aganglionosis with those of Hirschsprung's disease associated with Ondine's curse, another type of neurocristopathy.