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Amanda M. Jacobs, MD; Ivanka Toudjarska, MS; Andrew Racine, MD, PhD; Petros Tsipouras, MD; Michael W. Kilpatrick, PhD; Alan Shanske, MD

Arch Pediatr Adolesc Med. 2002;156:1081-1085.

Background  Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the fibrillin 1 gene (FBN1). FBN1 mutations have been associated with a broad spectrum of phenotypes. Neonatal Marfan syndrome has unique clinical manifestations and mutations.

Objective  To determine if there is a discernible genotypic-phenotypic correlation associated with the unique mutation in neonatal Marfan syndrome.

Study Design  A newborn exhibited many typical characteristics of neonatal Marfan syndrome, including arachnodactyly; contractures of both elbows, knees, and ankles; small-joint laxity; dilated cardiomyopathy; valvular dysplasia and insufficiency; congestive heart failure; and pulmonary emphysema. Three atypical features were also discovered: a right diaphragmatic hernia, a myocardial mass, and left main-stem bronchomalacia. She died at 3 months of age. Total RNA was extracted from skin fibroblasts and amplified by means of reverse transcriptase polymerase chain reaction amplification with FBN1-specific primers. The complementary DNA fragments were sequenced.

Results  A single T-to-C transition at nucleotide 3276 (T3276C) was identified and confirmed at the DNA level by sequencing of genomic DNA. This results in a substitution of threonine for isoleucine.

Conclusions  Neonatal Marfan syndrome is a unique clinical entity with recurring mutation hot spots in exons 24 to 27 and 31 to 32 of the FBN1 gene. Some clinical features in this case report are unusual for neonatal Marfan syndrome. This is the third report of this T3276C mutation in the FBN1 gene with unusual clinical manifestations. We conclude that there is a genotypic-phenotypic correlation associated with this mutation.

From the Department of Pediatrics (Drs Jacobs and Racine) and Center for Congenital Disorders (Dr Shanske), Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY; and Department of Pediatrics, University of Connecticut Health Center, Farmington (Ms Toudjarska and Drs Tsipouras and Kilpatrick).