Absence makes the search grow longer.

In this issue of the Journal, Casaubon and coworkers report mapping of the gene for Andermann syndrome or autosomal recessive agenesis of the corpus callosum and peripheral neuropathy to a 5-cM region in chromosome 15q13-15 (Casaubon et al. 1996).

Abstract

And longer. Much longer than for other brain malformations such as lissencephaly, holoprosencephaly, and even neural tube defects. The heterogeneity of agenesis of the corpus callosum (ACC) is so great that it will take decades rather than years to sort it out. And yet the genes responsible for ACC are an important part of the divine recipe for the human brain and should provide important insight regarding both normal and abnormal development of the brain. They are well worth the hunt. In this issue of the Journal, Casaubon and coworkers from McGill University in Montreal report mapping of the gene for Andermann syndrome (Andermann and Andermann 1994) or autosomal recessive agenesis of the corpus callosum and peripheral neuropathy (ACCPN) to a 5-cM region in chromosome 15q13-15 (Casaubon et al. 1996). While it may turn out to be simple coincidence, this region also proves to be one of several in which structural chromosome rearrangements have been associated with ACC. It therefore seems an opportune time to review the current status of the genetic map of ACC. ACC is among the most common brain malformatiops observed in humans, with an estimated incidence of 0.5 per 10,000 on the basis of autopsy series (Myrianthopoulos 1977), although other estimates have varied from 0.05 to 70 per 10,000 (Jeret et al. 1986). The prevalence in children with developmental disabilities is much higher, possibly as high as 230 per 10,000 (Jeret et al. 1986). ACC occurs as an isolated malformation and as one component of many different malformation syndromes. The basis for the extreme causal heterogeneity is best understood by reviewing the embryology of the corpus callosum, which shows that several different mechanisms can result in ACC.