Should chromosome breakage studies be performed in patients with VACTERL association?

Abstract

The VACTERL association is characterized as a non-random pattern of defects including at least three of the following cardinal features: vertebral anomalies, anal atresia, cardiovascular malformations, tracheoesophageal fistula, renal and limb anomalies, and is postulated to be a very heterogeneous disorder. These defects can also be seen as part of the Fanconi anemia (FA) spectrum. Although VACTERL with hydrocephaly has clearly been associated with FA, the indication for chromosome breakage studies is not clear in VACTERL without hydrocephaly. We report on three unrelated patients with the VACTERL phenotype and the confirmed diagnosis of FA. Together with the data of 13 similar cases extracted from a European genotype-phenotype correlation study for FA and those from the four reported cases of the literature, we show that (i) in a series of individuals proven to have FA, 5% (13/245) also have the VACTERL phenotype, (ii) all have radial ray anomalies and 12 of these 13 subjects show at least 1 other feature of FA (café au lait spots, growth retardation, microcephaly, dysmorphism), and (iii) the VACTERL phenotype appears to be over represented in the FA complementation groups D1, E, and F. Since the diagnosis of FA is important for genetic counseling and early therapeutic intervention in patients, we conclude that chromosomal breakage studies should be performed, not only in cases of VACTERL with hydrocephaly, but also in cases VACTERL with radial-ray anomalies and especially if the individual has additional FA associated manifestations such as skin pigmentation abnormalities, growth retardation, microcephaly, or microphthalmia.

• Authors: Laurence Faivre, Marie France Portnoï, Gerard Pals, Dominique Stoppa-Lyonnet, Martine Le Merrer, Christel Thauvin-Robinet, Frédéric Huet, Christopher G Mathew, Hans Joenje, Alain Verloes, Clarisse Baumann
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 137 Issue 1 Pg. 55-8 (Aug 15 2005) ISSN: 1552-4825 [Print] United States
• PMID: 16015582 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Topics

• Abnormalities, Multiple (genetics, pathology)
• Anus, Imperforate (pathology)
• Cardiovascular Abnormalities
• Child
• Child, Preschool
• Chromosome Breakage
• Fanconi Anemia (pathology)
• Fatal Outcome
• Female
• Humans
• Infant
• Karyotyping
• Kidney (abnormalities)
• Limb Deformities, Congenital (pathology)
• Male
• Spine (abnormalities)
• Tracheoesophageal Fistula (pathology)