2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Case Report: Prenatal Diagnostic Challenges in Familial Mediterranean Fever

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This case report discusses the challenges of prenatal diagnosis for familial Mediterranean fever (FMF), an autosomal recessive condition caused by variants in the MEFV gene. A 35-year-old pregnant patient and her partner were identified as carriers of variants in the MEFV gene through expanded carrier screening. During the current pregnancy, chorionic villus sampling and genetic testing were performed. The results indicated that the fetus inherited both FMF variants, but the paternal variant had been reclassified as a variant of uncertain significance (VUS) due to conflicting reports on its pathogenicity.<br /><br />The patient's 5-year-old daughter also tested positive for both FMF variants, but there are case reports of unaffected individuals who are compound heterozygous for these variants. While it is possible for FMF symptoms to develop later in life, most affected individuals develop symptoms in childhood. Based on the recent evidence and the current health status of the patient's daughter and other individuals in the literature, the likelihood of an affected pregnancy is significantly reduced.<br /><br />The complexity of predicting the clinical phenotype from prenatal genetic testing is highlighted in this case. The report emphasizes the importance of testing other family members to clarify the significance of fetal results. It suggests that the A744S variant, currently categorized as a VUS, may be considered for reclassification as a benign variant.<br /><br />In conclusion, this case report emphasizes the challenges in prenatal diagnosis for FMF and the complexity in predicting clinical phenotype from genetic testing. It highlights the importance of ongoing follow-up of family members to evaluate for symptoms of FMF and recommends further research to clarify the pathogenicity of the A744S variant.

Asset Subtitle

Presenting Author - Sarah Reiss, MS, CGC;

Meta Tag

Counseling

Genetic Testing

Genotype-Phenotype Correlations

Prenatal Diagnosis

Risk Assessment

Presenting Author Sarah Reiss, MS, CGC

Keywords

prenatal diagnosis

familial Mediterranean fever

FMF

autosomal recessive condition

MEFV gene

expanded carrier screening

chorionic villus sampling

genetic testing

variant of uncertain significance

compound heterozygous