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.

Abstract

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.

• Authors: Irene Bottillo, Marco Castori, Carmelilia De Bernardo, Romano Fabbri, Barbara Grammatico, Nicoletta Preziosi, Giovanna Sforzolini Scassellati, Evelina Silvestri, Antonella Spagnuolo, Luigi Laino, Paola Grammatico
• Journal: BMC research notes (BMC Res Notes) Vol. 6 Pg. 376 (Sep 22 2013) ISSN: 1756-0500 [Electronic] England
• PMID: 24053387 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RBM8A protein, human
• RNA-Binding Proteins

Topics

• Abnormalities, Multiple (diagnostic imaging, genetics, pathology)
• Adult
• Alleles
• Autopsy
• Chromosome Deletion
• Chromosomes, Human, Pair 1 (diagnostic imaging, genetics)
• Comparative Genomic Hybridization
• Congenital Bone Marrow Failure Syndromes
• Fatal Outcome
• Female
• Fetus (metabolism, pathology)
• Heterozygote
• Humans
• Male
• Megalencephaly (diagnostic imaging, genetics, pathology)
• Pedigree
• Pregnancy
• Prenatal Diagnosis
• RNA-Binding Proteins (genetics)
• Radiography
• Radius (diagnostic imaging, pathology)
• Syndrome
• Thrombocytopenia (diagnostic imaging, genetics, pathology)
• Upper Extremity Deformities, Congenital (diagnostic imaging, genetics, pathology)