*San Salvador, El Salvador C.A.

Definition:  Fraser syndrome^[1] consist of the association of four major characteristics (cryptophthalmos, syndactyly, genital anomalies and affected siblings) and eight minor characteristics (alterations of the nose, ears, larynx, oral clefts, umbilical hernia, renal agenesis, skeletal anomalies and mental retardation)^[2]. The diagnosis requires either the presence of 2 major and one minor characteristic, or one major and four minor characteristics^[3]. Cryptophthalmos is a rare congenital anomaly of the eye, characterized by continuity of the skin from the forehead to the cheek over a malformed eye. Cryptophthalmos is classified into three types: complete, incomplete and abortive^[4].

Synonyms:   Fraser syndrome, cryptophthalmos-syndactyly syndrome

Etymology:  Greek: kruptoV = cryptos = hidden and ofqalmos = ophtalmos = eye

Case report: This patient with no remarkable personal of familial anamnesis had no prenatal ultrasound. At delivery the newborn was found to have cryptophthalmos, hypertelorism, outer ear malformations with dysplastic pinna, cleavage along the midplane of the nose, hypoplastic notched upturned nostrils, oligodactyly with webbing of the fingers, widely spaced nipples, enlargement of the clitoris

Prevalence:  0.05:10,000 deliveries and 1.1:10,000 stillbirth¹.

Etiology and recurrence risk:  Autosomal recessive, the recurrence risk is thus 25%. About 15% of the parents are consanguineous^[5]. The clinical expression inside families is very constant with respect to cryptophthalmos, syndactyly and internal malformations^[6]. Further the families with fetuses with fatal outcome consistently have recurrent fatal outcome in affected siblings. This is important for genetic counseling: the discovery of a lethal form of the disease would recur, making identification at sonography particularly important.

Genetic anomaly: unknown

Pathogenesis: A defect of apoptosis has been suggested since several of the anomalies results from failure of programmed cell death (fusion of the eyelids, digits, larynx and the vagina)².

Sonographic findings^{[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]  ,}:

A case has been reported with monozygotic twins^[17].

Differential diagnosis: The differential diagnosis of the echogenic lungs includes congenital diaphragmatic hernia, cystic adenomatoid malformation (type III), sequestrated lung and tracheal or bronchial atresia. The differential diagnosis of the cryptophthalmos includes alobar holoprosencephaly which should be easy to recognize from the simple hydrocephalus of the Fraser fetuses and other crypto- anophtalmos without the associates malformations².

Associated anomalies^{[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34] ,}:

(numbers between parenthesis express reported frequencies)

Prognosis:   The prognosis depends on the severity of the renal and laryngeal malformations^[35],¹⁶. Overall 26% die as stillbirth and death occurs during the first year of life in another 19%³³.

Management: Prenatal: Termination of the pregnancy can be recommended when renal agenesis or laryngeal atresia is present. Postnatal: In selected cases of incomplete cryptophthalmos, oculoplastic and corneal surgery may result in some vision and in some eyelid movement^[36],^[37].

References:

See also Fraser syndrome

^[1] Fraser, G. R. : Our genetical "load:" a review of some aspects of genetical variation. Ann. Hum. Genet. 25: 387-415, 1962.

^[2] Thomas IT, Frias JL, Felix V, Sanchez de Leon L, Hernandez RA, Jones MC Isolated and syndromic cryptophthalmos. Am J Med Genet 1986 Sep;25(1):85-98

^[3] Martinez-Frias ML, Bermejo Sanchez E, Felix V, Calvo Celada R, Ayala Garces A, Hernandez Ramon F: Fraser syndrome: frequency in our environment and clinical-epidemiological aspects of a consecutive series of cases. An Esp Pediatr 1998 Jun;48(6):634-8

^[4] Kanhere S, Phadke V, Mathew A, Irani SF Cryptophthalmos. Indian J Pediatr 1999 Sep-Oct;66(5):805-8

^[5] Francois, J.Syndrome malformatif avec cryptophtalmie. Acta Genet. Med. Gemellol. 18: 18-50, 1969.

^[6] Lambert JC, Touitou I, Paquis V, Saunieres AM Expressivity of familial forms of Fraser syndrome. J Genet Hum 1989 Jun;37(2):119-26

^[7] Balci S, Altinok G, Ozaltin F, Aktas D, Niron EA, Onol B Laryngeal atresia presenting as fetal ascites, olygohydramnios and lung appearance mimicking cystic adenomatoid malformation in a 25-week-old fetus with Fraser syndrome. Prenat Diagn 1999 Sep;19(9):856-58

^[8] Lesniewicz R, Midro AT Ultrasound diagnosis of four fetuses with Fraser syndrome during pregnancy. Ginekol Pol 1998 Mar;69(3):152-7

^[9] Fryns JP, van Schoubroeck D, Vandenberghe K, Nagels H, Klerckx P Diagnostic echographic findings in cryptophthalmos syndrome (Fraser syndrome). Prenat Diagn 1997 Jun;17(6):582-4

^[10] Perez Aytes A, Fabregat Ferrer E, Ramos Fernandez V, Uixera Marzal L, Froufe Sanchez A Fraser syndrome, renal agenesis and fetal ascites. An Esp Pediatr 1993 Aug;39(2):163-6

^[11] Comas C, Martinez Crespo JM, Puerto B, Borrell A, Fortuny A Bilateral renal agenesis and cytomegalovirus infection in a case of Fraser syndrome. Fetal Diagn Ther 1993 Jul-Aug;8(4):285-90

^[12] Schauer GM, Dunn LK, Godmilow L, Eagle RC Jr, Knisely AS Prenatal diagnosis of Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks. Am J Med Genet 1990 Dec;37(4):583-91

^[13] Ramsing M, Rehder H, Holzgreve W, Meinecke P, Lenz W Fraser syndrome (cryptophthalmos with syndactyly) in the fetus and newborn. Clin Genet 1990 Feb;37(2):84-96