ESPE Yearbook of Paediatric Endocrinology

shenali.amaratunga@fnmotol.cz Horm Res Paediatr 2022; 95:1–11. doi: 10.1159/000521210

Brief Summary: This review highlights the value of consanguinity in the discovery of novel genes for three endocrine conditions with increasing pathophysiological complexity: congenital hyperinsulinism, monogenic diabetes and short stature.

This review nicely highlights that consanguinity has helped pediatric endocrinologists understand the pathophysiology of relatively common conditions. All medical students learn to ask about consanguinity, which is relatively easy to identify through interview of the patient and their family. It is more common in some regions of the world, including Asia, Africa, and the Middle East. Children of parents who are biologically inter-related have areas of genome homozygosity. However, it may be more difficult to identify whether an increased risk of homozygosity is present between parents who are not closely related. Pemberton et al. (1) introduced the concept of “runs of homozygosity (ROH)” and developed a population-wide method for identifying genomic segments that are sufficiently long to represent ROH. They devised a model-based clustering scheme that partitions the ROH of a population into three classes: short ROH, resulting from the pairing of ancient haplotypes; intermediate ROH, largely reflecting cryptic relatedness within populations or groups of populations; and long ROH, indicating recent consanguinity. This should be kept in mind when assessing recessive conditions in areas where the gene pool may be limited and when consanguinity between parents does not seem to be present.

Reference: 1. Pemberton TJ, Absher D, Feldman MW, Myers RM, Rosenberg NA, Li JZ. Genomic patterns of homozygosity in worldwide human populations. Am J Hum Genet. 2012; 91:275–292. DOI: 10.1016/j.ajhg.2012.06.014.