Counseling and management of a maternal diagnosis of mosaic trisomy 8 ascertained through prenatal cell-free DNA screening
Prenatal Genetics
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Primary Categories:
- Genetic Counseling
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Secondary Categories:
- Genetic Counseling
Introduction
Already a well-known potential consequence of fetal diagnostic testing, parental diagnosis may also occur after prenatal cell-free DNA screening (cfDNA) for aneuploidy. Chromosome 8 is the largest chromosome for which mosaic trisomy is compatible with life, while complete trisomy is lethal. A classic clinical presentation of mosaic trisomy 8 (T8M) was delineated over 20 years ago; however, only since cfDNA became the standard clinical practice has the breadth of cytogenetic and phenotypic variability of T8M become apparent. Although multiple sources have reported the detection of maternal T8M, almost no information on the counseling, management and outcome of these cases is available. The paucity of guidance may increase anxiety among clinicians and patients. This case of a manifesting patient who was diagnosed with constitutional T8M ascertained through cfDNA is also significant in that it highlights the importance of offering the appropriate cfDNA technology to provide patients, who have a chromosome abnormality, with equitable care.
Case Presentation
A 23-year-old G3P2 patient with an uncomplicated obstetric history presented to our department for a fetal anatomy survey at 29 weeks gestation because of two “no-call” cfDNA reports. Both the first and repeat specimen analyses for common aneuploidy and sex chromosome abnormalities performed on a genomic DNA library-based next-generation sequencing (NGS) platform returned “non-reportable”. Verbal communication between the laboratory and the referring provider reportedly conveyed that the data set was suspicious for a maternal abnormality involving chromosome 8, prompting a referral to our department for fetal anatomy survey and genetic counseling.
Diagnostic Workup
The fetal anatomy ultrasound, though suboptimal due to the advanced gestational age, returned within normal limits. The patient’s family medical history was non-contributory. The patient’s personal clinical history was notable for developmental delays, learning difficulties and an atypical facial morphology.
Treatment and Management
The patient’s gestational age precluded maternal serum screening for aneuploidy; therefore, the option of an alternate cfDNA through a single nucleotide variant-based (SNV-based) NGS platform focused on common aneuploidy detection was offered to the patient. The risks, benefits, and limitations of parental chromosome analysis, alternate cfDNA, and diagnostic fetal chromosome analysis were discussed. The patient elected personal cytogenetic analysis and the alternate cfDNA option. The patient declined fetal chromosome analysis through amniocentesis because of the risk for preterm labor.
Outcome and Follow-Up
Maternal cytogenetic analysis of 50 cells reported an abnormal mosaic female karyotype mos 47,XX+8[33]/46,XX[17]. Referrals to clinical medical genetics, oncology and cardiology were recommended for the patient. At 33 weeks 4 days we were able to reassure the patient that the fetal risk for trisomies 21, 18, 13, and monosomy X was low based on a low risk SNV-based cfDNA result. At 37 weeks 6 days the patient gave birth by spontaneous vaginal delivery to a healthy baby assigned female at birth with an Apgar score of 9. The patient and baby were discharged together.
Discussion
Here, we present a unique case of a maternal diagnosis of T8M for a manifesting patient from the initial non-reportable cfDNA result through delivery of a normal pregnancy. T8M is considered a sporadic condition with a low recurrence risk. While fetal prognosis is good, relevant maternal risks include malignancy, cardiac anomalies, and renal anomalies. No standardized national guidelines exist for appropriate management of the various types of incidental cfDNA findings. We applied genetic counseling, ultrasound, parental cytogenetic analysis, and a different cfDNA technology to provide the patient with the personal and prenatal risk assessment information the patient had requested.
Conclusion
T8M is the single most common autosomal aneuploidy detected as an incidental finding after cfDNA. This case reinforces the need for national cfDNA guidelines on the counseling, treatment and management of patients with non-reportable results or incidental findings of suspected maternal origin.
Already a well-known potential consequence of fetal diagnostic testing, parental diagnosis may also occur after prenatal cell-free DNA screening (cfDNA) for aneuploidy. Chromosome 8 is the largest chromosome for which mosaic trisomy is compatible with life, while complete trisomy is lethal. A classic clinical presentation of mosaic trisomy 8 (T8M) was delineated over 20 years ago; however, only since cfDNA became the standard clinical practice has the breadth of cytogenetic and phenotypic variability of T8M become apparent. Although multiple sources have reported the detection of maternal T8M, almost no information on the counseling, management and outcome of these cases is available. The paucity of guidance may increase anxiety among clinicians and patients. This case of a manifesting patient who was diagnosed with constitutional T8M ascertained through cfDNA is also significant in that it highlights the importance of offering the appropriate cfDNA technology to provide patients, who have a chromosome abnormality, with equitable care.
Case Presentation
A 23-year-old G3P2 patient with an uncomplicated obstetric history presented to our department for a fetal anatomy survey at 29 weeks gestation because of two “no-call” cfDNA reports. Both the first and repeat specimen analyses for common aneuploidy and sex chromosome abnormalities performed on a genomic DNA library-based next-generation sequencing (NGS) platform returned “non-reportable”. Verbal communication between the laboratory and the referring provider reportedly conveyed that the data set was suspicious for a maternal abnormality involving chromosome 8, prompting a referral to our department for fetal anatomy survey and genetic counseling.
Diagnostic Workup
The fetal anatomy ultrasound, though suboptimal due to the advanced gestational age, returned within normal limits. The patient’s family medical history was non-contributory. The patient’s personal clinical history was notable for developmental delays, learning difficulties and an atypical facial morphology.
Treatment and Management
The patient’s gestational age precluded maternal serum screening for aneuploidy; therefore, the option of an alternate cfDNA through a single nucleotide variant-based (SNV-based) NGS platform focused on common aneuploidy detection was offered to the patient. The risks, benefits, and limitations of parental chromosome analysis, alternate cfDNA, and diagnostic fetal chromosome analysis were discussed. The patient elected personal cytogenetic analysis and the alternate cfDNA option. The patient declined fetal chromosome analysis through amniocentesis because of the risk for preterm labor.
Outcome and Follow-Up
Maternal cytogenetic analysis of 50 cells reported an abnormal mosaic female karyotype mos 47,XX+8[33]/46,XX[17]. Referrals to clinical medical genetics, oncology and cardiology were recommended for the patient. At 33 weeks 4 days we were able to reassure the patient that the fetal risk for trisomies 21, 18, 13, and monosomy X was low based on a low risk SNV-based cfDNA result. At 37 weeks 6 days the patient gave birth by spontaneous vaginal delivery to a healthy baby assigned female at birth with an Apgar score of 9. The patient and baby were discharged together.
Discussion
Here, we present a unique case of a maternal diagnosis of T8M for a manifesting patient from the initial non-reportable cfDNA result through delivery of a normal pregnancy. T8M is considered a sporadic condition with a low recurrence risk. While fetal prognosis is good, relevant maternal risks include malignancy, cardiac anomalies, and renal anomalies. No standardized national guidelines exist for appropriate management of the various types of incidental cfDNA findings. We applied genetic counseling, ultrasound, parental cytogenetic analysis, and a different cfDNA technology to provide the patient with the personal and prenatal risk assessment information the patient had requested.
Conclusion
T8M is the single most common autosomal aneuploidy detected as an incidental finding after cfDNA. This case reinforces the need for national cfDNA guidelines on the counseling, treatment and management of patients with non-reportable results or incidental findings of suspected maternal origin.
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