OBJECTIVE
Expanded carrier screening (ECS) is rising in popularity because of its application
in a diverse population, its decreasing cost, and efficiency.
1
However, it has traditionally been used to assess fetal risk. The next generation
sequencing ECS panel offered at our academic medical center consists of 283 genes
associated with hereditary disorders. Of those, 20 (7.1%) are autosomal recessive
conditions, notable for variable expression of the clinical phenotype in heterozygous
carriers, which may increase maternal risk for malignancy, bleeding, cardiovascular,
or rheumatologic disease. Another 21 (7.4%) are X-linked conditions. We aimed to evaluate
the prevalence of variants that have a potential for maternal phenotypic expression
and whether identification of specific variants prompted patients to pursue further
care in our health system, namely comprehensive genetic counseling and further healthcare
consults when recommended.STUDY DESIGN
An institutional review board–approved descriptive retrospective cohort study was
performed in a New York City academic medical center at which reproductive aged women
were offered universal ECS from 2018 to 2021 by their provider, inclusive of obstetrician-gynecologists,
maternal-fetal medicine physicians, and genetic counselors. Pretest counseling was
performed by the ordering provider. Patients found to carry mutations with the potential
for maternal phenotypic expression were contacted by genetic counselors regarding
their clinical risks. In addition, patients who were carriers for factor XI deficiency,
Bernard Soulier syndrome, ataxia telangectesia, fumarase deficiency, Nijmegen breakage
syndrome, Duchenne muscular dystrophy, and familial hypercholesterolemia were advised
to seek specialized healthcare pertaining to their clinical risk. The genetic counseling
summary was placed in the electronic medical records (EMRs) so that the primary provider
could view the findings. Through our EMRs, we evaluated the rates of healthcare uptake
among these patients for at least 1 year after delivery.
RESULTS
In total, 168 of 1184 (14.2%) patients were identified as carriers of mutations with a
potential for maternal phenotypic expression. Of these, 156 (93%) were pregnant and
12 (7%) were preconception. Of those patients, 143 (85%) were carriers of autosomal
recessive traits (Figure 1), whereas 22 of 168 (13%) patients were carriers of X-linked
conditions (Figure 2) and 3 of 168 (2%) patients carried both autosomal recessive
traits and X-linked conditions. Of these carriers, 132 of 168 (78.6%) patients underwent
genetic counseling. The most common heterozygous mutations were sickle cell trait
(25.6%), thalassemia (alpha and/or beta) trait (14.2%), factor XI deficiency (4.7%),
dystrophic epidermolysis bullosa (4.2%), and Alport syndrome (4.1%). Two patients
were diagnosed as homozygous carriers of nonclassical congenital adrenal hyperplasia.
During the study period, 23 of 168 (13.6%) patients were heterozygous for specific
pathogenic variants (inclusive of factor XI, Bernard Soulier syndrome, ataxia telangectesia,
fumarase deficiency, Nijmegen breakage syndrome, Duchenne muscular dystrophy, and
familial hypercholesterolemia) and were advised to seek specialized healthcare pertaining
to these findings. Of these, 20 (87.0%) received genetic counseling with standardized
recommendations, however, only 4 of 23 (17%) patients pursued the recommended referrals
during our study period.
CONCLUSION
This study described the follow-up rates among patients identified as carriers of
conditions with the potential for maternal phenotypic expression using ECS. We observed
that 14.2% of patients who underwent ECS were identified as carriers of genetic mutations
with the potential for maternal phenotypic expression, and of the 23 who were recommended
specific care because a pathogenic variant was identified, only 17.4% of patients
followed the recommendations. We believe that as ECS implementation becomes widespread,
more maternal carriers with clinical risk to themselves will be identified. Therefore,
as we open this Pandora's box, the burden of counseling and follow-up must be addressed.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & Gynecology MFMAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
Reference
- Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).Genet Med. 2021; 23: 1793-1806
Article info
Publication history
Published online: November 27, 2022
Accepted:
November 22,
2022
Received:
November 13,
2022
Footnotes
The authors report no conflict of interest.
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
