Velo-Cardial-Facial Syndrome: A Model for Understanding Microdeletion Disorders, ed

The recognition of velo-cardio-facial syndrome as a specific congenital malformation syndrome is a relatively recent development for so common a disorder. The syndrome has appeared in the medical literature either as a specific and distinct diagnostic entity or as part of a discussion of broader symptoms (such as immune compromise, heart anomalies, or speech disorders) since the 1950s, but the majority of interest in the disorder did not develop until the 1990s. The earliest descriptions of the disorder were based on specific symptomatic presentations to clinicians who found the problems to be common among their caseloads. In 1978, in collaboration with a number of my colleagues, I specifically described ‘‘velocardio-facial syndrome’’ (a label I personally constructed) as a genetically caused multiple anomaly syndrome in 12 unrelated cases and one mother–daughter pair (Shprintzen et al., 1978). However, an earlier paper had already reported VCFS as a distinct syndrome in a single family that drew interest because of the presence of congenital heart anomalies and cognitive impairment (Strong, 1968), and descriptions of patients with VCFS from a symptomatic perspective can be found nearly 50 years ago in the Czechoslovakian medical literature (Sedlačková, 1955). Before going further, it would be useful for those readers who are not clinical geneticists or dysmorphologists to understand what the word ‘‘syndrome’’ connotes. Syndrome is defined as multiple anomalies in the same individual with all of those anomalies having a single cause (Smith, 1982; Shprintzen, 1997). This definition was agreed on by an International Working Group in order to differentiate the root causes of multiple anomaly disorders (Smith, 1982). Outside of the discipline of clinical genetics, the term ‘‘syndrome’’ is often applied in medicine to groupings of symptoms that do not meet the requirements for a multiple anomaly syndrome, such as postviral syndrome or AIDS (acquired immune deficiency syndrome). Familiar groupings of clinical findings are often referred to as syndromes consistent with the Greek roots for the word syndrome: syn meaning together and dramein meaning to run, or roughly translated as things that run together. However, as will be discussed later, not all things that run together meet the stricter criteria for syndrome in a genetic sense.