ClinVar

Wang et al. (1997) described 3 FBN1 mutations. Two of them were in patients with the neonatal form of Marfan syndrome (MFS; 154700); the third was in a patient with classic Marfan syndrome. All 3 occurred in the same region that had been found to harbor neonatal Marfan syndrome mutations. The first patient had striking skeletal features of Marfan syndrome, including soft, loose skin, crumpled ears, and joint contractures at birth. Eye and cardiac examinations were normal. At 7 months of age, he developed an aggressive scoliosis; however, his contractures were no longer evident. Hypotonia and marked mitral valve prolapse (which had not been evident at birth) were noted. At 14 months of age, an extensive mitral valve repair was performed. Postoperative complications necessitated replacement with a St. Jude mechanical prosthesis 3 weeks later and a porcine heterograft 2 months after the initial valve repair. At 20 months of age, he underwent plication of the right hemidiaphragm and resection of the bulbous cysts of the left lung. The patient died suddenly at 2 years of age. Diffuse changes of the Marfan syndrome were found in the vessels and emphysematous changes in the lungs at autopsy were noted. Amplified genomic DNA from the patient using intron primers to exon 25 showed heteroduplex formation when run on mutation detection enhancement (MDE) gels. Sequence analysis showed an A-to-G transition at position 3128 that caused a lysine-to-arginine substitution at amino acid position 1043 (K1043R) in 1 allele.