CONDITIONS AND SYNDROMES ASSOCIATED

WITH MICROPHTHALMIA

1. Chromosomal Anomalies.
• Triploidy.
• Trisomy 13.
• Partial trisomy 13.
• Trisomy 18.
• 4p-, 13q-, 18q-
• Trisomy 4p, trisomy 9 mosaic.
2. Infections / Environmental
• Fetal toxoplasmosis.
• Fetal rubella.
• Fetal varicella.
• Fetal alcohol syndrome.
• Maternal phenylketonuria.
3. Syndromes.
• CHARGE association.
• Fraser Syndrome (1-13) (cryptophthalmos-syndactyly syndrome) is an autosomal recessive multiple malformation syndrome whose major manifestations are cryptophthalmos, syndactyly, laryngeal atresia and urogenital defects. Enlarged hyperechogenic lungs contrasted by oligohydramnios, non-visualization of the kidneys and microphthalmia were sonographic markers leading to the prenatal detection of this rare autosomal recessive disorder in earlier reports.Variable expression of cryptophthalmos, syndactyly, abnormal genitalia, malformations of the nose, ear and larynx, renal agenesis, clefting, skeletal defects, umbilical hernia, and mental retardation in survivors. Other anomalies associated with Fraser syndrome are heart defects, major vascular anomalies, imperforate anus, intestinal hypoplasia, thymic aplasia, and cerebral malformations. Fraser syndrome has a recurrence risk of 25% among siblings, therefore prenatal diagnosis is an important task for the diagnostician counseling affected families. Prenatal diagnosis of Fraser syndrome has been reported in seven cases but the sonographic findings were very inconstant rendering the definition of sonographic markers difficult.

Thomas et.al. (14) describe strict major and minor criteria for diagnosis.

Major criteria: cryptophthalmos, syndactyly, abnormal genitalia and sib with cryptophthalmos syndrome.

Minor criteria: malformations of the nose ears or larynx, cleft lip and / or palate, umbilical hernia, renal agenesis, skeletal defects and mental retardation.

Diagnosis: At least two major and one minor criterion or on the basis of one major and at least four minor criteria.

• Goldenhar-Gorlin Syndrome.
• Frontonasal dysplasia.
• Lenz Syndrome (Coloboma, cataracts, Unilateral or bilateral renal agenesis)
• Goltz Syndrome.
• Hallerman-Streiff Syndrome (Frontal bossing, micrognathia, small beaked nose,dental anomalies, alopecia, microphthalmia, cataracts.
• Oculodentodigital Syndrome (Autosomal dominant, syndactyly, camptodactyly of 5th finger, thin hypoplastic nose)
• Pena-Shokeir II Syndrome.
• Facioauriculovertebral spectrum.
• Fanconi Syndrome.

REFERENCES

1. Karas DE & Respler DS. Fraser syndrome: a case report and review of the otolaryngologic manifestations. Int J Pediatr Otorhinolaryngol 1995; 31: 85-90
2. Ramsing M, Rehder H, Holzgreve W, Meinecke P, Lenz W. Fraser syndrome (cryptophthalmos with syndactyly) in the fetus and newborn. Clin Genet 1990; 37: 84-96
3. Feldman E, Shalev E, Weiner E, Cohen H, Zuckerman H. Microphthalmiaprenatal ultrasonic diagnosis: a case report. Prenat Diagn 1985; 5: 205-207
4. Ramsing M, Rehder H, Holzgreve W, Meinecke P, Lenz W. Fraser syndrome (cryptophthalmos with syndactyly) in the fetus and newborn. Clin Genet 1990; 37: 84-96
5. Boyd PA, Keeling JW, Lindenbaum RH. Fraser syndrome (cryptophthalmos-syndactyly syndrome): a review of eleven cases with postmortem findings. Am J Med Genet 1988; 31: 159-68
6. 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; 37: 583-591
7. Labbe A, Dechelotte P, Lemery D, Malpuech G. Pulmonary hyperplasia in Fraser syndrome. Pediatr Pulmonol 1992; 14: 131-134
8. Stevens CA, McClanahan C, Steck A, Shiel FO, Carey JC. Pulmonary hyperplasia in the Fraser cryptophthalmos syndrome. Am J Med Genet 1994; 52: 427-431
9. Fryns JP, van Schoubroeck D, Vandenberghe K, Nagels H, Klerckx P. Diagnostic echographic findings in cryptophthalmos syndrome (Fraser syndrome). Prenat Diagn 1997; 17: 582-584
10. Woodhead P & Hall C. Case report: Fraser syndrome, cryptophthalmos with small bowel malrotation. Clin Radiol 1990; 42: 362-363
11. Behrens-Baumann W, Dust G, Rittmeier K, Langenbeck U, Vogel M. Oculo-cerebral dysplasia: aplasia of the optic nerve with familial microphthalmos and cryptophthalmos. Clinical and computer tomography study. Klin Monatsbl Augenheilkd 1981; 179: 90-93
12. Balci S, Altinok G, Ozaltin F, Aktas D, Niron EA, Onol B. Laryngeal atresia presenting as fetal ascites, oligohydramnios and lung appearance mimicking cystic adenomatoid malformation in a 25-week-old fetus with Fraser syndrome. Prenat Diagn 1999; 19: 856-858
13. Gattuso J, Patton MA, Baraitser M. The clinical spectrum of the Fraser syndrome: report of three new cases and review. J Med Genet 1987; 24: 549-555
14. Thomas IT, Frias JL, Felix V et.al. Isolated and syndromic cryptophthalmos. Am J Med Genet 1986;25:85-89.
15. Vijayaraghavan SB, Suna N, Lata S et.al. Prenatal sonographic appearance of cryptophthalmos in Fraser syndrome. Ultrasound Obstet Gynecol 2005;25:629-630.