Microdeletion Syndromes

Overview

New high-resolution cytogenetical technique identified an increased number of terminal, interstitial and subtelomericmicrodeletion as the etiology of many syndromes of multiple congenital anomalies, mental retardation andfacial dysmorphy. A loss of contiguous genes shows a high phenotypical variability and at the same time it issignificant for genetic prognosis.1) Variability of clinical features depends on the size and pathogenetic mechanism of underlying deletion;2) Dysmorphic face features are of a characteristic type and can be somatoscopically recognized; 3) Heart defectsand mental retardation are common features of microdeletion syndromes; 4) New mutations represent the mostcommon etiology of microdeletions; only 1 to 10% of mutations are transmitted from the parental gonadal mosaics,from the balanced translocation or from the same microdeletion in parents; 5) Recurrence risk is low, but it may beas high as 50% in individual cases of inherited mutation; 6) Genetic heterogeneity is high and the responsible genescan be located at different chromosomes (e.g. Di George syndrome due to mutation on 22q or 10q) and can alsoresult from microdeletion or point mutation (in the Shprintzen syndrome 70 % represent microdeletion and 30 %point mutation at 22q11, in Rubinstein-Taybi syndrome 10 % cases result from microdeletions and 90% from pointmutations); 7) Population incidence ofmicrodeletions is high (1:4000 to 1:30 000) because their etiologicmechanismis related to the common unequal crossing over; 8) Imprinting plays a role in some cases, e.g. Prader-Willi syndromeresults from nullisomy of paternal 15q12 chromosome, Angelman syndrome is related to that of maternal 15q12chromosome; 9) Prenatal prevention of the high risk familial chromosomal rearrangements is feasible since the 12thgestation week.

Key words:
microdeletion, imprinting, contiguous genes, microdeletion syndromes, genetic prevention.