Background: Mothers are the main carers for their families, and they have a fundamental need to be knowledgeable of the potential health issues that their Down syndrome children can encounter. Aim: Assess knowledge, attitudes and reported practices of mothers with Down syndrome children. Setting: Nine schools for children with special needs at Kafr El-Sheikh Governorate. Numbers of all children with Down Syndrome affiliated to those schools constitute 120 children. Subjects: Mothers with Down Syndrome children attending schools for children with special needs. Tools: Tool (I): Mothers' Knowledge Structured Interview sheet, Tool (II): Mothers‟ Attitude Scale and Tool (III): Mothers' reported Practices toward their Down Syndrome Children Interview sheet. Results: Less than two-thirds of the studied children aged 5 to less than 10 years, and more than one half of them were male and in primary grades. Less than half of mothers had good knowledge about Down Syndrome compared to more than one tenth for poor knowledge. The majority of mothers had positive attitude toward Down syndrome child and the total mean score of mothers‟ practices were 56.7% for good practices. Conclusion: Study reveals that knowledge about Down syndrome was good among less than half of the mothers, and this was highly correlated with their practices. Also, most of mothers recognized the necessary of information for improving their attitudes toward DS. Recommendations: Provide life skills coaching program for the caregivers of DS children with the updated rearing practices.