On the website of Decipher, an updated list of all microdeletion and microduplication syndromes can be consulted.
More and more microduplication and microdeletion syndromes have been identified over the last few years, with the growing use of aCGH in research and clinical practice. They can be classified based on several criteria:
Recurrence criterion.
Recurrent CNVs
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1.
Pös O, Radvanszky J, Buglyó G, Pös Z, Rusnakova D, Nagy B, et al. DNA copy number variation: Main characteristics, evolutionary significance, and pathological aspects. Biomedical Journal [Internet]. 2021 Oct 1 [cited 2022 Aug 17];44(5):548–59. Available from: https://www.sciencedirect.com/science/article/pii/S2319417021000093
- They are flanked by short repetitive regions (LCRs, low copy repeats), which frequently give rise to breakpoints by NAHR (non-allelic homologous recombination).
- Multiple unrelated individuals share the same breakpoints.
- They are usually de novo.
- They occur more frequently than expected by the mutation rate, which is why they are comparatively more frequent.
Non-recurrent CNVs.
- They usually give rise to more variable phenotypes.
- They have different breakpoints for each individual/family, which have occurred randomly throughout the genome, resulting in deletion-duplication when repair mechanisms (NHEJ, non-homologous end-joining) have intervened.
- They are usually inherited, so the breakpoints will be characteristic of each family.
- There is a shared region in all individuals with the same syndrome (SRO, smallest region of overlap), which harbors the genes with phenotypic impact.
- They are less frequent.
Penetrance criterion
Complete penetrance CNVs
- They are "classic" syndromes, which were described based on the identification of the clinical phenotype.
- They are usually named with an eponym referring to the author who first described them.
- They tend to be "de novo", since the impact they have on individuals prevents their reproduction.
- Hover your mouse over the image to search for some of the different classic microdeletion syndromes.
Incomplete penetrance CNVs
- They are usually named after the chromosomal region they affect.
- They are "new" syndromes, most frequently identified through the implementation of molecular diagnostic techniques (aCGH).
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1.
Rosenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG. Estimates of penetrance for recurrent pathogenic copy-number variations. Genetics in Medicine [Internet]. 2013 [cited 2018 July 16];15(6):478–81. Available from: http://www.nature.com/articles/gim2012164
- They have incomplete penetrance, so there are asymptomatic carrier individuals, and familial transmission occurs more frequently from an individual who was unaware of their condition.
- In addition, the coexistence of multiple pathogenic variants in the same individual is more frequent.
