Survey Shows Gaps in Acceptance of Genetic Testing With Family Planning

Parents and relatives of those with Sanfilippo syndrome have a more positive perception of expanded carrier screening (ECS) for pregnancies than the general population, and are more likely to make use of it, according to a survey in the Netherlands.

Preconception expanded carrier screening is a comprehensive genetic test that determines the risk, for a couple planning a pregnancy, of the child being affected by one or more inherited genetic conditions.

The study also showed that genetic knowledge influenced ECS decision making, highlighting the need for appropriate information and counseling to allow for better informed reproductive decisions. That’s true not only for the general population, but also for relatives of patients with severe hereditary disorders.

The study, “Attitudes of relatives of mucopolysaccharidosis type III patients toward preconception expanded carrier screening,” was published in the European Journal of Human Genetics.

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is inherited in an autosomal recessive manner, meaning a child must acquire two defective copies of a disease-associated gene — one from the father and one from the mother — to develop the disease.

While people with only one mutated gene copy are typically healthy, they are called carriers because they can still transmit the mutated gene to their children. If both parents are carriers, their child has a 25% chance of developing the disease.

Carrier screening, preferably before a pregnancy, aims to detect carrier couples of autosomal recessive disorders to help them in making informed reproductive decisions. ECS involves the screening of a larger panel of such diseases, mostly those classified as severe and with a childhood onset (including Sanfilippo syndrome).

“Everyone is [a] carrier for one or several AR [autosomal recessive] disorders,” the researchers wrote, adding that “it is estimated that up to 2 in 100 couples in the general population is a carrier couple of a severe AR disorder.”

Previous studies have suggested that genetic knowledge and experiential knowledge — the knowledge gained from experience with the disease — influence and shape decisions related to genetic testing.

In agreement, studies in patients with an autosomal recessive disorder and their family members have shown that most are in favor of preconception carrier screening for the specific disorder in their family.

Now, researchers set out to compare the attitudes toward universal preconception ECS between parents and relatives of Sanfilippo syndrome patients and the general Dutch population, using an online questionnaire. Universal carrier screening is that offered to the general population, people without a known risk of being a carrier couple.

Parents of all Sanfilippo patients known to Amsterdam UMC’s specialized center were invited to participate in the questionnaire study, and those who agreed were asked to invite their first- and second-degree relatives to take part as well.

The survey included six domains: the intention to undergo ECS, the level of agreement on feelings toward ECS, the perceived benefits and barriers of ECS, the most important reasons in favor of and against ECS, the perceived social influences when considering ECS, and the perceived personal consequences of ECS.

Before the questionnaire, participants were given a brief educational text that included information on AR inheritance, on ECS (and its availably at that medical center), and on the clinical features of Sanfilippo syndrome as an example of the types of disorders included in ECS.

A brief genetic knowledge test (on AR inheritance and ECS) was used to verify if this educational text was understood.

Participants’ answers to the questionnaire were then compared with those previously collected from 781 people (ages 18–45) meant to reflect the general Dutch population. This group underwent identical preparation before answering the same questionnaire.

Perceived severity of Sanfilippo syndrome was also evaluated in both groups of participants.

In total, 58 out of 68 parents (85%) of 46 Sanfilippo patients, and 101 relatives participated in the study. Parents and relatives were significantly older, more often with a lower educational level, more often female, more often in a relationship, and considered less often a (future) pregnancy, compared with the general population.

Results showed that Sanfilippo parents and their relatives scored significantly better on the genetic knowledge test, and showed a higher perception of the disease’s severity than did participants from the general population.

In agreement, parents (84%) and relatives (63%) were significantly more likely to undergo ECS than the general population (31%). Notably, being a parent or a relative of a Sanfilippo patient was the strongest predictor of willingness to undergo ECS, even when controlled for sociodemographic factors.

Significantly more parents and caregivers also perceived more pros than cons of ECS, and agreed that every couple who wants to have children should take the carrier test.

“This study demonstrates a higher positive attitude of persons with genetic and experiential knowledge of a severe and yet untreatable AR disorder toward universal preconception ECS compared with participants of the Dutch general population,” the researchers wrote.

The absence of autosomal recessive disorders in the family was the most frequently selected reason against ECS by parents (37.9%) and participants from the general population (47.6%).

“This shows that even parents and relatives of patients with a very severe AR disorder appear to estimate their chances of being a carrier as low when there is no medical history in the family,” the researchers wrote.

These findings emphasized the importance of appropriate information and genetic counseling for informed reproductive decisions about ECS.

“This is not only important for the general population, but also for families with experiential and genetic knowledge to avoid misconceptions on this complex matter,” the team wrote.