Buenos Aires 01 de Agosto del 2020
Identical Twins are not Identical
Over the past few years it has become clearer that sequencing genes is a first step, but to understand complex diseases the next step is to look at factors that affect gene expression. Copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) interact with known syndrome or disease causing genes. CNVs and SNPs appear to influence single genes and multiple sites to produce complex diseases like Diabetes. Mapping all these SNPs or CNVs and assigning causative effects is in progress.
Every clinician has experienced patients with a known disease living far longer than expected or showing much milder effects than even a sibling. Split Hand syndrome with clefting of all four extremities in an infant can be passed by a parent who only has one shortened metacarpal, but has the same gene. Lack of penetrance or full penetrance of a gene at this time cannot be predicted, but it is assumed that CNVs, SNPs, and methylation may partially control penetrance.
In identical twins microarray studies of gene sequence demonstrates homology, but SNPs and CNVs can be different between the twins. So identical twins may express similar genes differently in regards to timing or severity of a genetic condition.
It is extremely critical for clinicians when offering a prognosis, to note the potential for variation of severity or duration of a known genetic condition. The "mean" is helpful, but it should not be a self-fulfilling prophecy which takes away all hope. Each individual can be unique in the course of their disease because of gene modification, as well as external influences such as hope and attitude. The clinician has the difficult task of balancing pessimism and optimism while presenting the "truth". Absolutes about expression of a genetic disease are becoming harder to understand since individuality occurs at the molecular level even in identical twins.
Understanding the role of CNVs and will be another important breakthrough for prognosis and treatment of genetic disorders.
Bruce Buehler, MD, Pediatrics