Case Report: Prenatal diagnosis of congenital knee dislocation caused by BICD2 gene variant

Congenital dislocation of the knee (CDK) is a rare malformation that severely affects the quality of life of affected fetuses and imposes a heavy burden on families and society. Its etiology remains unclear and may be related to genetic factors, quadriceps atrophy, muscular nutritional imbalance, and intrauterine factors. Here we report a case of CDK diagnosed prenatally by ultrasound in a 34-year-old pregnant woman at 25 weeks of gestation. Prenatal ultrasonography revealed knee hyperextension, abnormal hand morphology, and micrognathia. Exome sequencing identified a heterozygous mutation c.1613A>G (p.Tyr538Cys) in the BICD2 gene in the fetus, which was classified as likely pathogenic (PS2+PM2) according to American College of Medical Genetics and Genomics (ACMG) criteria. This variant is associated with autosomal dominant spinal muscular atrophy with lower extremity predominance type 2 (SMALED2). The prenatal ultrasound diagnosis was confirmed by autopsy after termination of pregnancy. This case expands the prenatal phenotypic spectrum of BICD2-related disorders by detailing the ultrasound features of CDK, highlights the diagnostic value of exome sequencing when fetal anomalies are detected prenatally, and is of great significance for the diagnosis of fetal congenital anomalies and the formulation of clinical management plans.