ß 2007 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 143A:875–880 (2007) Clinical Report Familial Neonatal Marfan Syndrome Due to Parental Mosaicism of a Missense Mutation in the FBN1 Gene Mustafa Tekin, 1 * Filiz Bas ¸ ak Cengiz, 1 Eda Ayberkin, 1 Tanıl Kendirli, 2 Suat Fitoz, 3 Ercan Tutar, 4 Ergin C ¸ iftc ¸i, 5 and Atakan Conba 2 1 Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey 2 Division of Pediatric Intensive Care Unit, Ankara University School of Medicine, Ankara, Turkey 3 Department of Radiodiagnostics, Ankara University School of Medicine, Ankara, Turkey 4 Division of Pediatric Cardiology, Ankara University School of Medicine, Ankara, Turkey 5 Division of Pediatric Infectious Disease, Ankara University School of Medicine, Ankara, Turkey Received 8 July 2006; Accepted 13 December 2006 We present a family in which three siblings were born with neonatal Marfan syndrome (MFS) to unaffected parents. The clinical findings included joint contractures, large ears, loose skin, ectopia lentis, muscular hypoplasia, aortic root dilata- tion, mitral and tricuspid valve insufficiency, and pulmonary emphysema. All three siblings died due to cardiorespiratory insufficiency by 2–4 months of age. Screening of the FBN1 gene showed the heterozygous c.3257G > A (p.Cys1086Tyr) mutation in the proband. Mosaicism of the mutation was demonstrated in the somatic cells and in the germ line of the father. Although three examples of parental mosaicism for classical MFS were demonstrated previously, this is the first report of familial occurrence of neonatal MFS due to a heterozygous mutation in FBN1. In conclusion, the p.Cys1086Tyr mutation in FBN1 is consistently associated with neonatal MFS. Parental mosaicism should always be kept in mind when counseling families with MFS. ß 2007 Wiley-Liss, Inc. Key words: cysteine residue; emphysema; fibrillin-1; mosaicism; neonatal Marfan syndrome How to cite this article: Tekin M, Cengiz FB, Ayberkin E, Kendirli T, Fitoz S, Tutar E, C ¸ iftc ¸ i E, Conba A. 2007. Familial neonatal Marfan syndrome due to parental mosaicism of a missense mutation in the FBN1 gene. Am J Med Genet Part A 143A:875 – 880. INTRODUCTION Marfan syndrome (MFS; OMIM 154700) is an autosomal dominant disorder of connective tissue that principally affects the skeleton, eyes, and cardiovascular system. The incidence of classic MFS has been estimated to be 2 – 3 per 10,000 individuals with no ethnic predilection [Judge and Dietz, 2005]. Approximately 25% of patients are sporadic due to de novo mutations [Gray et al., 1994]. After reviewing previously published reports and their own 22 patients, who were diagnosed by the age of 3 months with serious cardiac pathology, congenital contractures, distinctive facial features and a high mortality rate, Morse et al. [1990] delineated a subgroup in MFS referred to as infantile MFS. The most severely affected infants manifest life threatening phenotypic features, including pulmo- nary emphysema and mitral or tricuspid valve regurgitation at or soon after birth and are considered to have neonatal MFS [Hennekam, 2005]. The first gene responsible for MFS, FBN1, was discovered in 1991 [Dietz et al., 1991]. It contains 65 exons and codes for fibrillin-1, which is the main component of the extracellular microfibrils [Sakai et al., 1986]. Although intra- or interfamilial pheno- typic variability is the rule in MFS, genotype– phenotype correlations exist for some of the more than 600 published mutations [Robinson et al., 2002]. Described mutations are widespread throughout the gene and largely unique to each family. The most apparent genotype – phenotype correlation is for the *Correspondence to: Mustafa Tekin, Birlik Mah 65.Sok No:20/7, C¸ ankaya, Ankara 06610, Turkey. E-mail: mtekin@medicine.ankara.edu.tr DOI 10.1002/ajmg.a.31660