Sorted By Test Name - Mayo Medical Laboratories

FBNN
89314
features of Marfan syndrome, MASS phenotype, Shprintzen-Goldberg syndrome, and autosomal
dominant Weill-Marchesani syndrome
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Faivre L, Collod-Beroud G, Loeys BL, et al: Effect of mutation type and
location on clinical outcome of 1,013 probands with Marfan syndrome or related phenotypes and FBN1
mutations: an international study. Am J Hum Genet 2007 Sep;81(3):454-466 2. Tjeldhorn L,
Rand-Hendriksen S, Gervin K, et al: Rapid and efficient FBN1 mutation detection using automated
sample preparation and direct sequencing as the primary strategy. Genet Test 2006;10(4):258-264 3.
Boileau C, Jondeau G, Mizuguchi T, Matsumoto N: Molecular genetics of Marfan syndrome. Curr Opin
Cardiol 2005 May;20(3):194-200 4. Sood S, Eldadah ZA, Krause WL, et al: Mutation in fibrillin-1 and
the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Nat Genet 1996;12(2):209-211 2.
Faivre L, Gorlin RJ, Wirtz MK, et al: In frame fibrillin-1 gene deletion in autosomal dominant
Weill-Marchesani syndrome. J Med Genet 2003 Jan;40(1):34-36
FBN1, Partial Gene Sequence, Neonatal Marfan Syndrome
Clinical Information: Fibrillin-1 is a 320-kD cysteine-rich glycoprotein found in the extracellular
matrix. Monomers of fibrillin-1 associate to form microfibrils, which provide mechanical stability and
elastic properties to connective tissues. Fibrillin-1 is encoded by the FBN1 gene, which contains 65 exons
and is located at chromosome 15q21. FBN1 mutations are most commonly associated with Marfan
syndrome (MFS), an autosomal dominant connective tissue disorder involving the ocular, skeletal, and
cardiovascular systems. Ocular MFS manifestations most commonly include myopia and lens
displacement. Skeletal manifestations can include arachnodactyly (abnormally long and slender fingers
and toes), dolichostenomelia (long limbs), pectus (chest wall) deformity, and scoliosis. Cardiovascular
manifestations, which are the major cause of early morbidity and mortality in MFS, include aortic dilation
and aortic aneurysm and dissection, as well as mitral valve and tricuspid valve prolapse. There is
significant inter- and intrafamilial variability in phenotype. Neonatal MFS is characterized by a more
severe and rapidly progressing phenotype compared with classic MFS. Features can include congenital
contractures, dilated cardiomyopathy, congestive heart failure, pulmonary emphysema, and mitral or
tricuspid valve regurgitation in the newborn period. The majority of mutations associated with neonatal
MFS occur in exons 24 through 32. FBN1 mutations have also been reported in several other rare
phenotypes with variable overlap with classic MFS. These conditions include autosomal dominant ectopia
lentis (displacement of the lens of the eye), familial thoracic aortic aneurysm and dissection, isolated
skeletal features of MFS, MASS phenotype (mitral valve prolapse, aortic diameter increased, stretch
marks, skeletal features of MFS), Shprintzen-Goldberg syndrome (Marfanoid-craniosynostosis [premature
ossification and closure of sutures of the skull]), and autosomal dominant Weill-Marchesani syndrome
(short stature and short fingers, ectopia lentis). Hundreds of mutations have been identified in FBN1,
many of them unique to individual families. There is a wide range of variability, including intrafamilial
variability, in expressivity among FBN1 mutations. Approximately two thirds of FBN1 mutations are
missense mutations, with the majority of these being cysteine substitutions. Approximately 25% to 33%
of FBN1 mutations are de novo mutations, in which an individual has no family history of disease.
Genetic testing for FBN1 mutations allows for the confirmation of a suspected genetic disease.
Confirmation of neonatal MFS or other FBN1-associated genetic diseases allows for proper treatment and
management of the disease and preconception, prenatal, and family counseling.
Useful For: Aiding in the diagnosis of neonatal Marfan syndrome
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Morse RP, Rockenmacher S, Pyeritz RE, et al: Diagnosis and management
of infantile marfan syndrome. Pediatrics 1990;86(6):888-895 2. Putnam EA, Cho M, Zinn AB, et al:
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