Fraser Syndrome

This is a multiple malformation syndrome that may affect many parts of the body. Commonly, it is characterised by cryptophthalmos, syndactyly and renal defects. There may also be malformations of the nose, ears, throat and genitals and many other organs; mental retardation is not usually an accompaniment. The identification of the syndrome as being inherited in an autosomal recessive manner by Fraser in his 1962 paper, 'Our genetical load: a review of some aspects of genetical variation', Annals of Human Genetics< vol. 25 (1962), 387-415, p 400, led to V.A. McKusick styling it the Fraser Syndrome in the first edition of Mendelian Inheritance in Man (1966). In the 1990s the locus responsible for the condition was tentatively identified as being on chromosome 4 and in the early 2000s the gene involved was shown to be at chromosome 4q21 and was named FRAS1 in Fraser’s honour. The syndrome may also arise as a result of a mutation of the gene FREM2 on chromosome 13q, FREM being an acronym for FRAS-related extracellular matrix). Fraser heard about the FRAS1 gene for the first time at a talk by Peter J. Scambler at the European Society of Human Genetics meeting in May 2003.

Fraser gave accounts of his experience with cases of cryptophthalmos, its historical context and genetic causes in his lecture ‘Fraser Syndrome: two millennia of cryptophthalmos from Pliny the Elder to Peter Scambler via George Fraser', delivered at the Montreal Children's Hospital, Canada, 12 October 2007 and subsequently revised for a lecture at the Department of Medical Genetics, University of Geneva, Switzerland, 17 March 2008 (see H.38-H.42). His 2013 article "Fraser Syndrome: two millennia of cryptophthalamos from Pliny the Elder to FRAS. FREM and GRIP: a historical perspective" (Open Journal of Genetics, 2013, 3, 1-7) provides an overview.