This chapter reviews the archetypical chromosome disorder, namely Down syndrome (DS; trisomy 21), and the various different chromosomal forms that may be the basis of it: standard trisomy 21, translocation trisomy, both de novo and inherited, and other rare forms. The concept of dosage imbalance as the basis of the pathogenesis is reviewed, and the “DS critical region” on chromosome 21 is examined. Reproductive risks associated with each of these DS types are discussed. The chapter considers the other full autosomal trisomies, T13 and T18, and also (mosaic) T9. Triploidy, as the basis of hydatidiform mole, is reviewed. Also reviewed are the influence of parental, mostly maternal, age, in the genesis of these aneuploidies, and the effect of secular change on these observations. Tables provide precise age-related risk figures for recurrence risk of T21 and more general figures for other trisomies.
Localised Dominant Dystrophic Epidermolysis Bullosa with a Novel de Novo Mutation in COL7A1 Diagnosed by Next-generation Sequencing