Recent reports have described a distinct and recurrent pattern of systemic malformation that associates craniosynostosis and neurodevelop-mental abnormalities with many clinical features of the Marfan syndrome (MFS) 1–7, an autosomal dominant disorder of the extracellular microfibril caused by defects in the gene encoding fibrillin-1, FBN1(ref. 8). Additional common findings include other craniofacial anomalies, hypotonia, obstructive apnea, foot deformity, and congenital weakness of the abdominal wall. So far, only 11 cases have been reported1–7 precluding the assignment of definitive diagnostic criteria. While it remains unclear whether these cases represent a discrete clinical entity with a single aetiology, they have been pragmatically grouped under the rubric Marfanoid-craniosynostosis or Shprintzen-Goldberg syndrome (SGS). Because of the significant clinical overlap between MFS and SGS, we proposed that they may be caused by allelic mutations. We now report two SGS patients who harbour mutations in FBN1. While it remains unclear whether these mutations are sufficient for the clinical expression of the entire SGS phenotype, these data suggest a role for fibrillin-1 in early craniofacial and central nervous system development. Our recent observation that FBN1 transcript is expressed as early as the 8-cell stage of human embryogenesis is consistent with this hypothesis9.
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Sugarman, G. & Vogel, M.W. Craniofacial and musculoskeletal abnormalities. A questionable connective tissue disease. Synd. Iden. 7, 16–17 (1981).
Shprintzen, R.J. & Goldberg, R.B. A recurrent pattern syndrome of craniosynostosis associated with arachnodactyly and abdominal hernias. J. CraniofacialGenet Dev. Biol. 2, 65–74 (1982).
Furlong, J. Kurczynski, J. & Hennessy, J.R. . New Marfanoid syndrome with craniosynostosis. Am. J. Med. Genet. 26, 599–604 (1987).
Lacombe, D. & Battin, J. Marfanoid features and craniosynostosis: report of one case and review. Clin. Dysmorph. 2, 220–224 (1993).
Saal, H.M., Bulas, D.I., Fonda Alien, J., Vezina, G., Walton, D. & Rosenbaum, K.N. Patient with craniosynostosis and Marfanoid phenotype (Shprintzen-Goldberg syndrome) and cloverleaf skull. Am. J. Med. Genet. 57, 573–578 (1995).
Adés, L.C. et al. Distinct skeletal abnormalities in four girls with Shprintzen-Goldberg syndrome. Am. J. Med. Genet. 57, 565–572 (1995).
Kosztolanyi, G., Weisenbach, J. & Méhes, K. Syndrome of arachnodactyly, disturbance of cranial ossification, protruding eyes, feeding difficulties, and mental retardation. Am. J. Med. Genet. 58, 213–216 (1995).
Dietz, H.C. et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin. gene. Nature. 352, 337–339 (1991).
Eldadah, Z.A., Grifo, J.A. & Dietz, H.C. Marfan syndrome as paradigm for transcript-targeted preimplantation diagnosis of heterozygous mutations. Nature Med. 1, 798–803 (1995).
Hewett, D.R., Lynch, J.R. & Sykes, B.C. A new missense mutation of fibrillin in a patient with Marfan syndrome. J. Med. Genet. 31, 338–339 (1994).
Tynan, K. et al. Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains. Hum. Mol. Genet. 2, 1813–1821 (1993).
Dietz, H.C. & Pyeritz, R.E. Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders. Hum. Mol. Genet. 4, 1799–1809 (1995).
Nijbroek, G. et al. Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons. Am.J. Hum. Genet. 57, 8–21 (1995).
Dietz, H.C. et al. Marfan phenotype variability in a family segregating a missense mutation in the epidermal growth factor-like motif of the fibrillin gene. J. Clin. Invest. 89, 1674–1680 (1992).
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