Search

We report the identification of a novel mutation in the fork-head box C1 ( FOXC1 ) gene which occurred de novo in an Italian patient with unrecognized Axenfeld–Rieger syndrome. He was previously diagnosed as having late recognized primary congenital glaucoma at the age of 14 years and was subsequently subjected to multiple surgical interventions due to uncontrolled intraocular pressure and progressive visual field loss. After exclusion of mutations in CYP1B1 and MYOC , trio-whole-exome sequencing revealed de novo in frame deletion in the coding region of the FOXC1 gene (c.407_409delGTC, p.V137del) leading to a deletion of the evolutionary conserved amino acid Valine at position 137 of the protein. Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding capacity and transcriptional activation. Since loss-of-function mutations in FOXC1 are associated with Axenfeld–Rieger syndrome, the genetic findings in combination with re-evaluation of the patient's clinical data resulted in a corrected diagnosis of Axenfeld–Rieger syndrome with developmental glaucoma. We therefore suggest that in addition to CYP1B1 and MYOC , FOXC1 should be included in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure proper diagnosis, adequate treatment and appropriate genetic counseling. [ABSTRACT FROM AUTHOR]

Purpose To review the clinical variations and natural course of Coats disease. Methods We reviewed our experience with clinical features, staging and progression of the disease. In 37 consecutive patients, Coats disease was diagnosed in 15 under the age of 4y and in 22 over the age of 4y. All 37 patients had unilateral disease. The referral diagnoses were Coats disease and retinoblastoma. Patients in both groups (<4y and >4y) were classified into Stages 1 to 5. Results 15 out of 37 patients were diagnosed under the age of 4y (mean age 2.1y) and were Stage 4 and 5 at diagnosis. In the older group (>4y – mean age 7.1y) most cases were Stage 2 and 3; only one case was Stage 4. Most cases of the first group (<4y) presented a rapid progression of the disease, while older children with earlier stages have been successfully treated. Conclusion Coats disease is much more aggressive in very young children (<4y). Children diagnosed at an early age present a rapid progression to total exudative detachment, secondary glaucoma and phthisis. One of these cases presented Stage 5 disease at diagnosis with cholesterolosis of the anterior chamber. Older Children present a rather slow progression, a better response to treatment and a better visual prognosis. [ABSTRACT FROM AUTHOR]

Purpose We report two (twin A and twin B) cases of unilateral retinoblastoma in identical female twins with 13q deletion syndrome. Family history for retinoblastoma was negative. Karyotypic analyses (peripheral lymphocytes) of the brother and their parents showed no abnormalities. Methods Twin A has demonstrated unilateral, multifocal retinoblastoma (left eye), diagnosed at the age of 5 months, which was recalcitrant to systemic chemoreduction, than treated with intraarterial chemotherapy. Twin B has demonstrated unilateral unifocal retinoblastoma (right eye) at 9 months of age, successfully treated with brachytherapy. Both had prominent eyebrows, broad nasal bridge, large, prominent, low – set ears, bulbous tipped nose, large mouth, and thin upper lip. MRI revealed ventricles dilatation associated with corpus callosum agenesis. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single‐stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. Results Molecular genetic analyses confirmed monozygosity. Conclusion We describe two cases of 13q deletion syndrome in bicorial identical twins. [ABSTRACT FROM AUTHOR]