NON-TRADITIONAL FORMS OF INHERITANCE THAT ARE RELEVANT FOR PEDIATRIC ENDOCRINOLOGY

Abstract

Developments in molecular genetics have made it possible to recognize many new mechanisms of disease. These are particularly important to the pediatric endocrinologist since they explain a number of observations and disorders.Mosaicism is seen frequently in disorders of growth. It explains many cases of intrauterine growth retardation, asymmetry, overgrowth and cancer. Patchy disorders such as McCune Albright are being recognized to have patches of abnormal cells interspersed with normal cells. Depending on the distribution of those cells, various systems may be involved to different degrees.Imprinting (parental origin effect) has been recognized as playing a role in a number of disorders of growth including Prader Willi, Weidemann Beckwith and pseudohypoparathyroidism. Specific growth factors may have expression from only one parent.Uniparcntat disomy occurs when both chromosomes of a pair come from only one parent. This situation appears to be much more common than previously suspected and may explain both the occurrence of autosomal recessive disorders and disorders having to do with growth, behaviour and survival.These previously unrecognized mechanisms appear to be relatively common explanations for disease processes. They can account for transgenerational effects and for the non-penetrance and variability which has been observed in the past. It is important to consider them as possible explanations for rare and unusual disorders.