Indian Pediatrics 2003; 40:888-890 

Fraser-Cryptophthalmos Syndrome with Cardiovascular Malformations: A Rare Association

Fraser-Cryptophthalmos syndrome is an autosomal recessive(1), multiple malformation disorder; first described by Zehender and Manz(2) in 1872 and further delineated by Fraser(3). Cryptophthalmos (hidden eye) means failure of development of lid-folds which may be associated with anomalies of the head, nose and ears; syndactyly, renal and genital malformations. In this report, we describe a case of Fraser syndrome with cardiovascular malformations; including coarctation of aorta, an association not previously described.

Case Report

The preterm (30 weeks) male, was the third child born to nonconsanguinous Indian parents. The first was a full term normal child, three years old. The second was a full term home-delivered fresh stillbirth without history of obvious congenital malformations. Baby’s birthweight was 1.7 kg, head circumference 30 cm, total length 41 cm, chest circumference 29 cm, abdominal girth 21 cm and upper segment: lower segment ratio of 1.38 : 1.

The face revealed absence of eyelids and eyebrow over the left eye (Fig. 1). It was completely covered with skin; the globe was palpable underneath. Right eye showed microphthalmia and enophthalmos. Nose was broad, flat with a depressed nasal bridge and a groove present bilaterally on the external nares. Ears were low set with nonpatency of the external auditory canal. There was microg-nathia, high arched palate and a cleft in the hard palate. Hands were flat, stubby with cutaneous syndactyly. Elbows showed presence of webs and limited extension. Genital examination showed rudimentary, empty scrotal sacs; with clinical patency of anal canal found upto 0.5 cm.

Fig. 1. Fraser’s syndrome showing typical facial features and syndactyly.

Skeletal system revealed a right-sided thoracic spinal scoliosis and bilateral con-genital talipes equinovarus. Systemic examina-tion was unremarkable except hypotonia. Inspite of vigorous resuscitation the baby expired within one hour of life. Significant post-mortem findings included bilateral renal agenesis and cardiac malformations; viz., bifid apex, large atrioseptal defect, juxtaductal coarctation of the aorta, left superior vena cava draining into the coronary sinus and a patent ductus arteriosus.

Discussion

Fraser’s syndrome is a well delineated multiple malformation complex with a marked variability of expression. Thomas, et al.(4) reviewed 124 cases of cryptophthalmos in literature and assigned minimal diagnostic criteria to designate Fraser’s syndrome. This included two major and one minor criteria or one major and four minor criteria for diagnosis. Major criteria include cryptophthalmos, syndactyly, abnormal genitalia, and a sibling with cryptophthalmos syndrome. Minor criteria comprise of anomalies of ear, nose or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation.

Our patient definitely fulfilled two of the major criteria and five of the minor criteria. Regarding abnormal genitalia, empty scrotal sacs could be normal for the gestational age and there was a possible anal stenosis. Also, cause of stillbirth in the second sibling was not known. In addition, he also had cardiovascular mal-formations, which are unusual. Gattuso, et al.(5) reported dextrocardia; and their literature review reported 3 other cases having univentricular heart, atrial septal defect and ventricular septal defect. Ali, et al.(6) reported a newborn with Fraser syndrome, born of consanguinous Saudi parents, having cardiac malformations (TAPVR and pericardial effusion) diagnosed on fetal echocardiography. Our case had multiple cardiovascular mal-formations, including coarctation of aorta.

The pathogenesis of this syndrome appears to be related either to a failure of programmed cell necrosis(7) or a defect in the metabolism of retinoids(8). There is no treatment available if renal agenesis is present. Prognosis is excellent if cryptophthalmos is the main abnormality, but visual acuity is likely to be poor even after surgical correction. Although abnormalities of the ear are common, hearing is usually normal in many cases(5). Severe bilateral renal dysplasia or agenesis implies no prospect for survival. Also, cardiac malformations, as seen in our case, carry grave prognosis. Prenatal diagnosis includes a combination of ultrasound and fetoscopy(9), though prevention by genetic counseling would be the best approach.

Acknowledgements

The authors acknowledge and thank our Dean, Dr. S.A. Dahanukar for granting us permission to publish the case report.

Contributors: SDH contributed in data collection. PPB reviewed the literature, drafted the manuscript and will act as guarantor. MB contributed the autopsy diagnosis. AVJ helped in revision of the manuscript and final approval of the version submitted.

Funding: None.

Competing interests: None stated.

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