Apert Syndrome in the Era of Prenatal Diagnosis

Abstract

Apert syndrome is a rare autosomal dominant disorder charac terized by severe craniosynostosis, hypoplastic mediofacial structures and symmetric syndactyly. The syn dactyly involves both cutaneous and osseous structures of the upper and lower limbs. Apart from skeletal anomalies, affected fetuses may often present central nervous system malformations and various visceral malformations (congenital heart defects, genitourinary ano malies, choanal stenosis, tracheal abnormalities, dia phrag matic hernia and omphalocele). Mental retardation is frequently encountered, as are a large variety of craniofacial and neurocognitive phenotypes. The incidence of Apert syndrome is approximately one in 65,000 newborns, representing 4.5% of all cranio synostosiscases.ThefirstcasesofApertsyndromewere diagnosed by ultrasound and fetoscopy in the third trimester of pregnancy. With the introduction of threedimensional (3D) ultrasonography,identificationoffetalchangescharacteristicof Apert syndrome is possible in the second trimester of pregnancy. DiagnosisconfirmationrequiresfetalDNAanalysisbyfibroblast growthfactorreceptor2geneamplification(FGFR2)followed bysequencinganddigestionwithrestrictionenzymes.Recently, noninvasive prenatal diagnosis was reported using free fetal DNA analysis with cell-free fetal DNA (cffDNA) in maternal plasma by Polymerase Chain Reaction (PCR) assay and enzymatic digestion with restriction enzymes. As the syndrome hasrarelybeenreportedinRomania,wepresentthecaseofa fetus diagnosed with Apert syndrome in the second trimester of pregnancy. Early ultrasound detection of suggestive signs for this syndrome (craniosynostosis, syndactyly) was followed by confirmationofthediagnosisbyprenatalfetalDNAanalysis.