2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Fetal Genome Sequencing for Multiple Congenital Anomalies Identifies a Likely Pathogenic Variant in the <em>CHD2</em> Gene: A Case Report

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A 29-year-old pregnant woman was urgently referred to Maternal Fetal Medicine due to concerns about multiple fetal anomalies on ultrasound. Recommendations were made for amniocentesis, referral to an Advanced Fetal Care Center, and fetal MRI. The fetal MRI revealed several abnormalities, including a transsphenoidal encephalocele, midline cleft lip, hypertelorism, blunted appearance of the nose, and agenesis of the corpus callosum with associated colpocephaly. Whole Genome Sequencing (WGS) was performed, which identified a de novo, heterozygous, likely pathogenic variant in the CHD2 gene.<br /><br />Heterozygous loss-of-function CHD2 gene mutations are associated with Developmental and Epileptic Encephalopathy 94 (DEE94), a severe form of epilepsy characterized by seizures, intellectual disability, and cognitive regression. Most cases of CHD2-related neurodevelopmental disorders are de novo mutations and are typically diagnosed in childhood after the onset of seizures or intellectual disability. Structural brain abnormalities are uncommon in association with CHD2 gene variants, but a few individuals may show atrophy, corpus callosum hypoplasia, cerebellar atrophy, and Chiari malformation type 1 on brain MRI.<br /><br />The pregnancy ended in elective termination. This case is the first documented case of CHD2-related neurodevelopmental disorder associated with fetal ultrasound abnormalities and diagnosed from fetal WGS. The findings potentially expand the clinical phenotype of CHD2-related neurodevelopmental disorders. Further studies are needed to determine if there are genotype-phenotype correlations that correlate with in utero abnormalities and provide recommendations for prenatal WGS. The report also discusses the identification of a likely pathogenic variant in the CHD2 gene and the potential association of these in utero abnormalities with specific alterations within the gene.<br /><br />This case highlights the importance of fetal imaging and genetic testing in diagnosing and understanding neurodevelopmental disorders. Retrospective review of fetal anatomy scans in patients diagnosed with CHD2 gene alterations during childhood could provide more information on the rates of similar scan abnormalities.

Asset Subtitle

Co-Author - Samantha Bookbinder, BS; Co-Author - Neena L. Champaigne, MD; Presenting Author - Paige Babb, CGC;

Meta Tag

Brain/Nervous System

Fetal Pathology

Genetic Testing

Identification of Disease Genes

Prenatal Diagnosis

Ultrasound

Co-Author Samantha Bookbinder, BS

Co-Author Neena L. Champaigne, MD

Presenting Author Paige Babb, CGC

Keywords

fetal anomalies

ultrasound

fetal MRI

CHD2 gene

Developmental and Epileptic Encephalopathy 94

seizures

intellectual disability

corpus callosum hypoplasia

prenatal WGS

neurodevelopmental disorders