Fraser Syndrome 1

Clinical Characteristics

Ocular Features:

Cryptophthalmos is the major ocular malformation in Fraser syndrome but is a feature in only 93% of patients. The globe is often small and sometimes completely absent or in some cases consisting of only rudimentary ocular tissue. The cornea is often adherent to the eyelid tissue. The lacrimal ducts may be deformed or absent and the lids are often fused.

Systemic Features:

The most common malformations seen in this disorder are syndactyly (61.5%), cryptophthalmos (88%), and genitourinary malformations but others of a great variety have also been reported, such as laryngeal stenosis, deafness, and deformities of the nares and external auditory meati. Ambiguous genitalia occur in 17%. Some infants are stillborn and many do not survive the neonatal period. Cognitive deficits and congenital heart disease are common.

Genetics

Fraser syndrome 1 is caused by homozygous or heterozygous mutations in the FRAS1 [1] gene (4q21.21).

Fraser syndrome 2 [2] (617666 [3]) results from homozygous mutations in the FREM2 [4] gene (13q13.3). Parental consanguinity is common (25%) and familial patterns are consistent with autosomal recessive inheritance.

Fraser syndrome 3 [5] (617667 [6]) results from homozygous mutations in the GRIP1 [7] gene (12q14.3). Three consanguineous families have been reported.

Mutations in GRIP1 [7] (PAD14 [8]) (12q14.3) have also been found in 3 families in which the parents were consanguineous.

Isolated cryptophthalmos [9] (123570 [10]) also occurs in autosomal dominant pedigrees as well as sporadically. It is rarely found as an incidental feature of other syndromes.

Treatment

Treatment Options:

No treatment is available.

References

Article Title:

Molecular study of 33 families with Fraser syndrome new data and mutation review [11]

van Haelst MM, Maiburg M, Baujat G, Jadeja S, Monti E, Bland E, Pearce K; Fraser Syndrome Collaboration Group, Hennekam RC, Scambler PJ. Molecular study of 33 families with Fraser syndrome new data and mutation review. Am J Med Genet A. 2008 Sep 1;146A(17):2252-7.

PubMed ID:

18671281

Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes [12]

Slavotinek AM, Tifft CJ. Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet. 2002 Sep;39(9):623-33. Review.

PubMed ID:

12205104

Fraser syndrome (cryptophthalmos-syndactyly syndrome): a review of eleven cases with postmortem findings [13]

Boyd PA, Keeling JW, Lindenbaum RH. Fraser syndrome (cryptophthalmos-syndactyly syndrome): a review of eleven cases with postmortem findings. Am J Med Genet. 1988 Sep;31(1):159-68.

PubMed ID:

2851937

Multiple congenital abnormalities associated with cryptophthalmia [14]

Ide CH, Wollschlaeger PB. Multiple congenital abnormalities associated with cryptophthalmia. Arch Ophthalmol. 1969 May;81(5):638-44.

PubMed ID:

4305611