Thrombocytopenia-absent radius (TAR) syndrome: A clinical genetic series of 14 further cases. Impact of the associated 1q21.1 deletion on the genetic counselling

• Published in: European journal of medical genetics Vol. 54; no. 5; pp. e471 - e477
• Main Authors: Houeijeh, Ali, Andrieux, Joris, Saugier-Veber, Pascale, David, Albert, Goldenberg, Alice, Bonneau, Dominique, Fouassier, Marc, Journel, Hubert, Martinovic, Jelana, Escande, Fabienne, Devisme, Louise, Bisiaux, Sophie, Chaffiotte, Caroline, Baux, Mathilde, Kerckaert, Jean-Pierre, Holder-Espinasse, Muriel, Manouvrier-Hanu, Sylvie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01.09.2011
• Subjects: 1q21.1 deletion; Adult; Child; Chromosome Deletion; Chromosomes, Human, Pair 1 - genetics; Ectromelia - diagnostic imaging; Female; Genetic Counseling; Genetic counselling; Humans; Male; Medical Education; Phenotype; Prenatal diagnosis; Radial aplasia; Radiography; Radius - abnormalities; Radius - diagnostic imaging; Sex Factors; TAR syndrome; Thrombocytopenia - diagnostic imaging; Thrombocytopenia - genetics; Upper Extremity Deformities, Congenital - diagnostic imaging; Upper Extremity Deformities, Congenital - genetics; Young Adult; TAR syndrome; 1q21.1 deletion; Radial aplasia; Prenatal diagnosis; Genetic counselling
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2011.05.001

Abstract Thrombocytopenia-absent radius Syndrome (TAR) is a rare congenital malformation syndrome of complicated transmission. 1q21.1 deletion is necessary but not sufficient for its expression. We report the result of a French multicentric clinical study, and we emphasized on the role of the associated 1q21.1 deletion in the diagnosis and the genetic counselling of our patients. We gathered information on 14 patients presenting with TAR syndrome and referred for genetic counselling in six different university hospitals (8 foetuses, 1 child and 5 adults). Clinical or pathology details, as well as skeletal X-rays were analyzed. Genetic studies were performed by Array-CGH, and Quantitative Multiplex PCR. We demonstrated the very variable phenotypes of TAR syndrome. Female:male ratio was ∼2:1. All patients presented with bilateral radial aplasia/hypoplasia with preserved thumbs. Phocomelia and lower limb anomalies were present in 28% of the cases. We reported the first case of cystic hygroma on affected foetus. 1q21.1 deletions ranging from 330 to 1100 kb were identified in all affected patients. Most of them were inherited from one healthy parent (80%). The identification of a 1q21.1 deletion allowed confirmation of TAR syndrome diagnosis, particularly in foetuses and in atypical phenotypes. Additionally, it allowed accurate genetic counselling, especially when it occurred de novo . These findings allowed discussing the diagnostic criteria and management towards TAR syndrome.