The association of craniosynostosis with ectopia lentis is rare. A review of the literature revealed that most reported cases of craniosynostosis with ectopia lentis are sporadic in nature. Recently, Cruysberg et al [AJMG 82:201-205 (1999)] reported on monozygotic twin sisters with craniosynostosis and ectopia lentis, supporting a genetic etiology for this association. The authors hypothesized that the occurrence of craniosynostosis and ectopia lentis in their case was most likely due to an autosomal dominant new mutation. We report on female first cousins once-removed who were born with a constellation of findings similar to those reported by Cruysberg et al. One cousin was born with unilateral coronal synostosis, and peripheral pulmonic branch stenosis. At 3 months of age she was found to have ectopia lentis. The other cousin was also born with unilateral coronal synostosis, an atrial septal defect and mitral valve prolapse. She has only mild myopia. Both females are of normal intelligence. There is no other family history of craniosynostosis, ectopia lentis or congenital heart defect. There is no consanguinity. The family is of German/English descent. Mutation analysis for the FGFR2, FGFR3, and TWIST genes was negative. Chromosome analysis was normal. Homocystinuria was also ruled out.
We believe this case supports an autosomal dominant etiology for the association of Craniosynostosis and ectopia lentis and further defines this syndrome to include congenital heart defects. The additional finding of congenital heart defects in our case has not been previously reported in association with craniosynostosis and ectopia lentis. Furthermore, the presence of coronal synostosis in first cousins once-removed in this family supports the notion that this is an autosomal dominant condition with reduced penetrance. These findings will have important implications for genetic counselling.
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Ouercia, N., Teebi, A. Craniosynostosis, ectopia lentis and congenital heart defect: further delineation of an autosomal dominant syndrome with reduced penetrance. Genet Med 2, 85 (2000). https://doi.org/10.1097/00125817-200001000-00122