Prenatal diagnosis and post-mortem examination in a fetus with thrombocytopenia-absent radius (TAR) syndrome due to compound heterozygosity for a 1q21.1 microdeletion and a RBM8A hypomorphic allele: a case report

摘要

Background Thrombocytopenia–absent radius syndrome is a rare autosomal recessive disorder characterized by megakaryocytic thrombocytopenia and longitudinal limb deficiencies mostly affecting the radial ray. Most patients are compound heterozygotes for a 200 kb interstitial microdeletion in 1q21.1 and a hypomorphic allele in RBM8A , mapping in the deleted segment. At the moment, the complete molecular characterization of thrombocytopenia–absent radius syndrome is limited to a handful of patients mostly ascertained in the pediatric age Case presentation We report on a fetus with bilateral upper limb deficiency found at standard prenatal ultrasound examination. The fetus had bilateral radial agenesis and humeral hypo/aplasia with intact thumbs, micrognathia and urinary anomalies, indicating thrombocytopenia–absent radius syndrome. Molecular studies demonstrated compound heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant at the hemizygous state, inherited from the mother and father, respectively Conclusion The molecular information allowed prenatal diagnosis in the following pregnancy resulting in the birth of a healthy carrier female. A review was carried out with the attempt to the trace the fetal ultrasound presentation of thrombocytopenia–absent radius syndrome and discussing opportunities for second-tier molecular studies within a multidisciplinary setting.