Wolf-Hirschhorn syndrome with intrauterine growth restriction in a fetus: A case report

Abstract

Introduction: Wolf-Hirschhorn syndrome (WHS), a genetic syndrome caused by deletion of the short arm of chromosome 4 (4p), is clinically characterized by “Greek warrior helmet” facial appearance, growth retardation, intellectual disability, seizures, skeletal anomalies, congenital cardiovascular defects, and other systemic defects. The severity of the WHS phenotype is related to the size of the missing 4p terminal fragment. In this article, we report and analyze a case of atypical WHS manifestations that revealed a 21-Mb deletion of the 4p terminal fragment in prenatal amniotic fluid examination by copy number variation sequencing (CNV-seq). Patient concerns: In our case, the fetal ultrasound results presented with intrauterine growth restriction and ocular hypertelorism and were characterized by atypical manifestations such as persistent left superior vena cava, nuchal fold thickness, and extrahepatic portosystemic shunt at 21 + 6 weeks of gestational age. Diagnosis: A fetus with WHS was detected by noninvasive prenatal screening and further diagnosed by chromosome karyotype analysis and CNV-seq. Interventions: After genetic counseling, the couple opted to terminate her pregnancy. Outcomes: Cytogenetic examination of the fetus revealed karyotype 46,XX,del(4)(p15.3). The CNV results showed a 21-MB deletion at the 4p16.3-p15.31 locus. Lessons: The WHS phenotype is atypical in fetuses. Prenatal molecular genetic testing combined with ultrasound screening is an effective method for diagnosing fetal WHS and can help clinicians offer subsequent clinical genetic counseling, manage fetal WHS, and guide the next pregnancy.