IVF May Be Linked to Increased Risk of Angelman Syndrome, Study Suggests

Ashraf Malhas, PhD avatar

by Ashraf Malhas, PhD |

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In vitro fertilization (IVF) appears to increase the risk of Angelman syndrome as a result of a genetic mechanism known as an imprinting error, according to a study of IVF pregnancies.

Several studies have indicated that IVF is accompanied by an increased risk of certain conditions with imprinting disorders, such as Angelman, Beckwith-Wiedemann syndrome, and Russell-Silver syndrome. But there have been very few studies exploring Angelman syndrome and IVF.

A small number of of Angelman cases (2-5%) are caused by imprinting errors, cases in which the gene associated with the disease mechanism is not mutated but is instead “switched off” through epigenetic mechanisms. These mechanisms, unlike gene mutations, are reversible and are usually used to fine-tune the activity of a gene.

However, in the case of imprinting errors, these mechanisms lead to the complete loss of gene function.

The study, “Detection of a case of Angelman syndrome caused by an imprinting error in 949 pregnancies analyzed for AS following IVF,” published in the Journal of Assisted Reproduction and Genetics, reported a case of Angelman syndrome in a series of IVF pregnancies, confirming that IVF increases the risk for this disease.

The study included 949 IFV pregnancy cases. Fetal DNA was isolated from cells and analyzed using assays that can detect epigenetic changes associated with imprinting disorders.

Researchers detected one case of Angelman syndrome caused by an imprinting error in a pregnancy of identical twins.

Angelman syndrome has an overall frequency of about 1 in 10,000 to 1 in 20,000 births. Using the highest estimates, the frequency of Angelman syndrome caused by imprinting errors in the general population is therefore expected to be about 1 in 200,000 births.

But in this study, the frequency was 1 in 949 in a group of IVF cases, leading researchers to hypothesize that IFV significantly increases the risks of developing Angelman syndrome as a result of imprinting errors. This association could be due to the clinical procedures undertaken during IVF.

It is important to note, however, that the study is limited by its small sample size, and samples came from a limited number of prenatal centers in the U.S.

Additional studies with larger samples are necessary to further investigate this hypothesis. But according to the researchers, “the risk for an imprinting disorder such as [Angelman syndrome] following IVF could be high enough to warrant prenatal diagnosis and, at a minimum, counseling concerning the risk.”