From its first description in antiquity, the place of cryptophthalmos in the history of medical genetics is briefly set out until, in the twentieth century, this rare constellation of multiple congenital malformations of which cryptophthalmos is the most striking, even though not obligatory, component, was identified as an inherited autosomal recessive condition. It was given the name of Fraser syndrome and mutant alleles of the genes FRAS1, FREM2 and GRIP1 were identified as being responsible for a proportion of cases. In the remainder of cases, it may be supposed that mutant alleles of other genes, as yet unidentified, are responsible. In general, this association of multiple disparate malformations in an autosomal recessive condition may be expected to throw light on important aspects of gene action in embryogenesis. An aspect of medical genetics, which has become important with respect to the condition, is antenatal diagnosis with the prospect of abortion of affected fetuses.
 Lejeune, J., Gautier, M. and Turpin, R. (1959) Etude des chromosomes somatiques de neuf enfants mongoliens. Comptes Rendus Hebdomadaires des Séances de l’Académie des Sciences (Paris), 248, 1721-1722.
 Fraser, G.R. and Friedmann, A.I. (1967) The causes of blindness in childhood. A study of 776 children with severe visual handicaps (with preface by L. S. Penrose). Johns Hopkins Press, Baltimore.
 Fraser, G.R. (1976) The causes of profound deafness in childhood. A study of 3535 individuals with severe hearing loss present at birth or of childhood onset (with foreword by V. A. McKusick). Johns Hopkins University Press, Baltimore and London.
 Little, C.C. and Bagg H.J. (1924) The occurrence of four inheritable morphological variations in mice and their possible relationship to treatment with X-rays. Journal of Experimental Zoology, 41, 45-91. doi:10.1002/jez.1400410106
 McGregor, L., Makela, V., Darling, S.M., Vrontou, S., Chalepakis, G., Roberts, C., et al. (2003) Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nature Genetics, 34, 203-208. doi:10.1038/ng1142
 Vrontou, S., Petrou, P., Meyer, B.I., Galanopoulos, V.K., Imai, K., Yanagi, M., et al. (2003) Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice. Nature Genetics, 34, 209-214. doi:/10.1038/ng1168
 Pitera, J.E., Scambler, P.J. and Woolf, A.S. (2008) Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Human Molecular Genetics, 17, 3953-3964. doi:10.1093/hmg/ddn297
 van Haelst, M.M., Maiburg, M, Baujat, G, Jadeja, S, Monti, E., Bland, E., et al. (2008) Molecular study of 33 families with Fraser syndrome: New data and mutation review. American Journal of Medical Genetics Part A, 146A, 2252-2257. doi:10.1002/ajmg.a.32440
 Vogel, M.J., van Zon, P., Brueton, L., van Gijzen, M., van Tuil, M.C., Cox, P., et al. (2012) Mutations in GRIP1 cause Fraser syndrome. Journal of Medical Genetics, 49, 303-306. doi:10.1136/jmedgenet-2011-100590
 Slavotinek, A.M. and Tifft, C.J. (2002) Fraser syndrome and cryptophthalmos: Review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. Journal of Medical Genetics, 39, 623-633. doi:10.1136/jmg.39.9.623
 van Haelst, M.M., Scambler, P.J., Fraser Syndrome Collaborative Group and Hennekam, R.C.M. (2007) Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria. American Journal of Medical Genetics Part A, 143A, 3194-3203. doi:10.1002/ajmg.a.31951
 Slavotinek, A.M., Baranzini, S.E., Schanze, D., Labelle-Dumais, C., Short, K.M., Chao, R., et al. (2011) toba-oculo-tricho-anal(MOTA) syndrome is caused by mutations in FREM1. Journal of Medical Genetics, 48, 375-382. doi:10.1136/jmg.2011.089631
 Kohl, T., Hering, R., Bauriedel, G., van de Vondel. P., Heep, A., Keiner, S., et al. (2006) Percutaneous feto-scopic and ultrasound-guided decompression of the fetal trachea permits normalization of fetal hemodynamics in a human fetus with Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia. Ultrasound in Obstetrics and Gynecology, 27, 84-88. doi:10.1002/uog.1974
 Yap-Todos, E. and Yap, D. (2007) Michele, Florina, and George Fraser: The cryptophthalmos story at the human level. In: Mayo, O. and Leach, C., Eds., Fifty Years of Human Genetics: A Festschrift and Liber Amicorum to Celebrate the Life and Work of George Robert Fraser. Wakefield Press, Kent Town, 299-308.