TARP syndrome

TARP syndrome is an extremely rare, severe X-linked lethal multiple congenital anomaly syndrome. The acronym TARP stands for its four cardinal features: Talipes equinovarus (clubfoot), Atrial septal defect, Robin sequence (micrognathia, glossoptosis, and cleft palate), and Persistent left superior vena cava. The condition is caused by mutations in the RBM10 gene located on the X chromosome, which encodes an RNA-binding protein involved in alternative splicing regulation. TARP syndrome predominantly affects males and is typically lethal in utero or in the neonatal period. The syndrome affects multiple body systems. Cardiac abnormalities are a hallmark and may include atrial septal defects, ventricular septal defects, and other structural heart malformations, including the characteristic persistent left superior vena cava. Craniofacial features include Pierre Robin sequence with severe micrognathia (small jaw), cleft palate, and glossoptosis (posterior displacement of the tongue), which can cause significant airway obstruction. Skeletal abnormalities include bilateral talipes equinovarus (clubfoot). Additional features that have been reported include brain abnormalities such as cerebellar hypoplasia, syndactyly, polydactyly, and abnormalities of the auditory system. Affected males frequently present with hydrops fetalis or severe polyhydramnios prenatally. Due to the extremely high lethality of TARP syndrome in affected males, there is no established curative treatment. Management is supportive and palliative, focusing on airway management, cardiac stabilization, and comfort care. Carrier females are generally unaffected or may show very mild features. Genetic counseling is essential for families with a known RBM10 mutation. Prenatal diagnosis is possible through molecular genetic testing when the familial mutation has been identified. Fewer than 20 cases have been reported in the medical literature.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about TARP syndrome