The clinical spectrum of complete allele deletions

Abstract The most common mutations found in are missense mutations (56%) mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift mutations, splice mutations and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a allele. We describe the clinical features of 10 patients with a complete gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patients were examined at a young age and did not (yet) present the full clinical picture of MFS yet. Ectopia lentis was present in at least two patients. Aortic root dilatation was present in six of the 10 patients. In three patients, the aortic root diameter was on the 95th percentile and in one patient the diameter of the aortic root was normal, the cross-section however had a clover-leaf appearance. Two patients underwent aortic root surgery at a relatively young age (27 and 34 years old). Mitral valve prolapse was present in four of 10 patients and billowing of the mitral valve in one. All patients had facial and skeletal features of MFS. Two patients with a large deletion extending beyond the gene had an extended phenotype. We conclude that complete loss of one allele does not predict a mild phenotype and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.