PLA2G6-Associated Neurodegeneration: Prenatal Counseling and Diagnostic Testing in a Couple Heterozygous for a Pathogenic Variant

Document Type

Conference Proceeding

Publication Date

2026

Publication Title

Genetics in Medicine Open

Abstract

Treatment and Management: The patient and her partner were counseled regarding the results of diagnostic testing and that the fetus was expected to be unaffected by PLA2G6-associated neurodegeneration. They opted to continue the pregnancy. She has been receiving routine prenatal care from her obstetric team. Outcome and Follow-Up: Thus far, the pregnancy has remained uncomplicated. A detailed anatomy ultrasound at 20 weeks did not demonstrate any structural anomalies or abnormalities. Discussion: Identification of familial pathogenic variants allows for targeted, efficient, and cost-effective prenatal diagnosis while minimizing invasive testing and uncertainty. Although most published reports focus on postnatal clinical presentation and disease progression, few describe real-world applications of variant-specific testing in subsequent pregnancies. This case highlights how genetic counseling can tailor prenatal testing strategies to a patient’s values, reproductive history, and risk tolerance, ultimately supporting informed reproductive decision-making. Conclusion: Access to prompt prenatal diagnostic testing and counseling allows for optimal reproductive decision-making and autonomy. Additional case reports involving PLA2G6 pathogenic variants are needed to strengthen the evidence base guiding prenatal counseling and decision-making. Introduction: PLA2G6-associated neurodegeneration (PLAN) represents a spectrum of autosomal recessive neurodegenerative disorders caused by biallelic pathogenic variants in the PLA2G6 gene. The phenotypic spectrum includes infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and dystonia-parkinsonism. The age of onset ranges from infancy to adulthood. Infantile forms may present with symptoms such as psychomotor regression, hypotonia, hyperreflexia, and seizures, typically beginning between six months and three years of age. PLAN is rare, with few reports describing prenatal diagnostic decision-making in couples who are known to carry pathogenic variants. The specific PLA2G6 pathogenic variant described in this case has not yet been reported in the context of prenatal diagnostic evaluation. There are few reports of the variant in the literature, and it is not currently reported in population databases. This case highlights the role of prenatal counseling and targeted familial variant testing for PLA2G6-associated conditions. Case Presentation: A 38-year-old gravida 9, para 4 woman was referred to genetics at 12 weeks and 5 days gestation due to a known family history of PLAN. The couple are first cousins, and both are unaffected heterozygotes of the pathogenic variant c.1117G>A (p. G373R) in PLA2G6. The couple’s first three children were affected by PLAN and died at ages 11, 10, and 9 years. Their second child underwent exome sequencing, which identified homozygous pathogenic variants. All three affected children experienced hypotonia, developmental regression, and developmental delay. There were no reported abnormal prenatal ultrasound findings in these pregnancies. Their fourth child was found to be heterozygous for the pathogenic variant in PLAG2G6 via amniocentesis prenatally and is unaffected. Their following three pregnancies were found to be affected by the homozygous pathogenic variants via amniocentesis and CVS utilizing targeted familial variant analysis and were electively terminated. The current pregnancy was spontaneously conceived and has been uncomplicated. Diagnostic Workup: At the time of referral, a transabdominal ultrasound demonstrated a single live intrauterine pregnancy without sonographic markers of aneuploidy or structural anomalies. Options for prenatal diagnostic testing were reviewed, including chorionic villus sampling (CVS) and amniocentesis. The benefits and limitations of various testing modalities—including FISH, karyotype, chromosomal microarray (CMA), and targeted familial variant analysis—were reviewed. Given the established familial PLA2G6 variant, the patient elected to pursue CVS with targeted familial variant testing only. Targeted analysis from CVS revealed that the fetus was heterozygous for the PLA2G6 c.1117G>A pathogenic variant.

Volume

4

Issue

Suppl 1

First Page

104271

Comments

2026 ACMG (American College of Medical Genetics) Annual Clinical Genetics Meeting, March 10-14, 2026, Baltimore, MD

Last Page

104271

DOI

10.1016/j.gimo.2026.104271

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