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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Novel Prenatal Phenotype of Biallelic mutations in ...
Novel Prenatal Phenotype of Biallelic mutations in SLC5A6; expanding the phenotypic spectrum
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This document describes a case of a novel prenatal phenotype of biallelic mutations in SLC5A6. SLC5A6-related disorder is a rare autosomal recessive inborn error of metabolism that presents with neurocognitive regression, failure to thrive, and musculoskeletal differences. The SLC5A6 gene encodes for the sodium-dependent multivitamin transport protein, which is responsible for transporting biotin, pantohenate, and lipoate across the blood-brain barrier and gastrointestinal tract. Most reported cases of biallelic pathogenic variants in SLC5A6 have been in pediatric patients with progressive neurodegenerative diseases. However, this case is the first to describe the structural brain abnormalities associated with this condition prenatally.<br /><br />The case involves a 28-year-old pregnant woman who underwent prenatal evaluation due to suspected fetal ventriculomegaly. Ultrasound and MRI imaging revealed severe ventriculomegaly, delayed sulcation and gyration, dysmorphic basal ganglia, and small brainstem and cerebellum. Genetic testing confirmed compound heterozygous variants in the SLC5A6 gene, resulting in loss of function and impairment of the B vitamin cofactors.<br /><br />The authors highlight the clinical utility of whole exome sequencing in diagnosing neurological differences prenatally. Detecting this disease prenatally allows for pregnancy management options and the possibility of delivering in a tertiary care center with timely intervention of triple vitamin replacement therapy postnatally to improve outcomes. The authors also raise the question of whether future potentially affected pregnancies could benefit from prenatal vitamin replacement therapy as a preventative measure.<br /><br />In this case, the patient chose to terminate the pregnancy due to the imaging and genetic testing findings. The family subsequently conceived another pregnancy and the pregnant patient began taking oral biotin, panthothenic acid, and α-lipoic acid daily. Although second-trimester imaging was normal, it is unclear if variable expressivity is contributing to the lack of findings. The impact of prenatal vitamin therapy in individuals with this disorder is unknown due to limited prenatal case reports and most individuals presenting postnatally.
Asset Subtitle
Submitter Only - Erica Schindewolf, MS; Co-Author - Julie Moldenhauer, MD, FACOG, FACMG; Co-Author - Ana Cristancho, MD; Presenting Author - ERICA MA. SCHINDEWOLF, MS, LCGC;
Meta Tag
Brain/Nervous System
Exome sequencing
Prenatal Diagnosis
Co-Author
Julie Moldenhauer, MD, FACOG, FACMG
Co-Author
Ana Cristancho, MD
Presenting Author
ERICA MA. SCHINDEWOLF, MS, LCGC
Submitter Only
Erica Schindewolf, MS
Keywords
prenatal phenotype
biallelic mutations
SLC5A6-related disorder
neurocognitive regression
structural brain abnormalities
fetal ventriculomegaly
genetic testing
compound heterozygous variants
whole exome sequencing
prenatal vitamin replacement therapy
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