Fraser Cryptophthalmos Syndrome

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.  In some cases it consists of only rudimentary ocular tissue.  The cornea is often adherent to the eyelid tissue.  The lacrimal ducts may be deformed or absent.

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.  Mental retardation and congenital heart disease are common.

Genetics

This malformation syndrome is genetically heterogeneous with some cases due to a mutation in the FRAS1 gene (13q13.3) and others by mutations in the FREM2 gene (4q21).  Parental consanguinity is common (25%) and familial patterns are consistent with autosomal recessive inheritance. 

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

Isolated cryptophthalmos  (123570) 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: 

Fraser Syndrome

Saleem AA, Siddiqui SN. Fraser Syndrome. J Coll Physicians Surg Pak. 2015 Oct; 25(10 Suppl) :S124-6.

PubMed ID: 
26522198

Mutations in GRIP1 cause Fraser syndrome

Vogel MJ, van Zon P, Brueton L, Gijzen M, van Tuil MC, Cox P, Schanze D, Kariminejad A, Ghaderi-Sohi S, Blair E, Zenker M, Scambler PJ, Ploos van Amstel HK, van Haelst MM. Mutations in GRIP1 cause Fraser syndrome. J Med Genet. 2012 Apr 17. [Epub ahead of print].

PubMed ID: 
22510445

References

Saleem AA, Siddiqui SN. Fraser Syndrome. J Coll Physicians Surg Pak. 2015 Oct; 25(10 Suppl) :S124-6.

PubMedID: 26522198

Vogel MJ, van Zon P, Brueton L, Gijzen M, van Tuil MC, Cox P, Schanze D, Kariminejad A, Ghaderi-Sohi S, Blair E, Zenker M, Scambler PJ, Ploos van Amstel HK, van Haelst MM. Mutations in GRIP1 cause Fraser syndrome. J Med Genet. 2012 Apr 17. [Epub ahead of print].

PubMedID: 22510445

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.

PubMedID: 12205104

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.

PubMedID: 2851937

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

PubMedID: 4305611