Fetal chondrodysplasia punctata: a clinical study of five cases

BACKGROUND: Chondrodysplasia punctata (CDP) is characterized by irregular calcification of the epiphyseal cartilage in the neonatal or infant period, which is determined by both genetic and non-genetic factors. OBJECTIVE: To explore the prenatal ultrasonographic manifestations, genetic etiology, and pregnancy outcomes of fetal CDP. METHODS: Five fetuses from three families diagnosed with CDP by prenatal ultrasound were retrospectively analyzed, and the clinical features, genetic testing results, and pregnancy outcomes of the CDP cases were analyzed. RESULTS: Prenatal ultrasound showed strong punctate echogenicity of the long diaphyseal epiphysis (mainly in the femur, tibia, and humerus) in all five fetuses. Four fetuses (4/5, 80%) had short long bones. Three fetuses (3/5, 60%) had spinal anomalies and one (1/5, 20%) had Binder syndrome. Cataracts were present in two fetuses (2/5, 40%). Genetic testing was performed on all five fetuses. Chromosome karyotype and chromosomal microarray analysis showed no abnormalities. However, some region-specific pathogenic variants were identified in whole exome sequencing. Labor was induced in four fetuses. Only one fetus was delivered at 39 weeks of gestation, transferred to the Department of Pediatrics for respiratory support due to dyspnea after birth, and had a good prognosis with follow-up. CONCLUSION: Fetuses diagnosed with CDP mostly exhibit genetic abnormalities and adverse neonatal outcomes. Fetuses with punctate strong echogenicity of the long diaphyseal epiphysis and short long bones identified on ultrasound must be comprehensively screened for other systemic malformations, particularly spinal dysplasia and facial malformations. Genetic testing is recommended.