Whole exome sequencing combined with dynamic ultrasound assessments for fetal skeletal dysplasias: 4 case reports

Fetal skeletal anomalies are one of the most common and potentially pathogenic developmental abnormalities detected by ultrasound screening. Any suspected fetal skeletal dysplasias often require further comprehensive evaluations. PATIENT CONCERNS: Here 4 families with adverse fetal skeletal system histories were enrolled, including their histories of gestation, childbirth, familial skeletal abnormalities, and pregnancy outcomes. The corresponding diagnosis were done by whole exome sequencing (WES) combined with dynamic examination. DIAGNOSIS: All of the families were definitively diagnosed through cytogenetics, molecular genetics, ultrasound, combined with multidisciplinary evaluation. Both of the fetuses in case 1 and case 2 were diagnosed with thanatophoric dysplasia type I, while the neonate in case 3 was diagnosed with Apert syndrome and a 3-years-old proband daughter with Crouzon syndrome in case 4. INTERVENTIONS: We conducted karyotyping, copy number variation sequencing (CNV-seq), combined with WES to evaluate genetic conditions of abnormal fetus, neonate or proband patient. WES was preferred to obtain a relatively definitive diagnosis. OUTCOMES: In cases 1 and 2, the families decided to choose termination of pregnancy due to fatal dysplasias. The couple in case 3, delivered a female baby diagnosed with Apert syndrome. Fortunately, in case 4, the family, which had a 3-years-old baby with Crouzon syndrome, gave birth to a healthy baby through prenatal diagnosis. LESSONS SUBSECTIONS: Invasive prenatal diagnosis and dynamic assessments for the management of fetal skeletal dysplasias could contribute to revealing possible causes of fetal skeletal abnormalities and help clinicians conduct further genetic counseling in clinical practice.