Spondylo-ocular syndrome: a new entity with crystalline lens malformation, cataract, retinal detachment, osteoporosis, and platyspondyly.

PURPOSE: To define a new clinical entity in a consanguineous family with six children affected by a spondylo-ocular syndrome, including cataract, crystalline lens malformation, retinal detachment, osteoporosis, and platyspondyly. To analyze candidate genes of connective tissue disorders as a possible underlying disorder and to demonstrate especially the ocular phenotype. DESIGN: Observational case series. METHODS: Consanguineous parents, one unaffected sibling and five affected children with clinical features of spondylo-ocular syndrome, were demonstrated. Clinical examination, radiologic, laboratory, and cytogenetic as well as moleculargenetic analyses were performed. The segregation of flanking marker alleles of three collagen genes and the interval for osteoporosis-pseudoglioma syndrome were analyzed. Two microsatellite markers located within Pax6CA/GT region were tested for homozygosity. RESULTS: On laboratory investigation a normal excretion of amino acids, mucopolysaccharides, and oligosaccharides could be found. The karyotype was normal. Complete radiologic examination in one index patient revealed a generalized moderate osteoporosis, platyspondyly with fish bone appearance, and greatly enlarged intervertebral spaces. The candidate genes known to be in Stickler syndrome as well as linkage to the osteoporosis-pseudoglioma syndrome candidate region could be excluded. None of the affected showed homozygosity for the Pax6 microsatellite markers. CONCLUSIONS: We conclude that the phenotype and the clinical features in this family defines a new Mendelian disorder. It remains to be seen what kind of molecule shared by eye and bone is involved.

Phenotypic variability in three carriers from a family with choroideremia and a frameshift mutation 1388delCCinsG in the REP-1 gene.

PURPOSE: To perform genotype-phenotype correlations in a family with choroideremia. METHODS: A three-generation family with two affected males and five carriers was the subject of the study. Molecular genetic analysis using single-strand conformation polymorphism analysis (SSCP) was conducted in all subjects, while electroretinography (ERG), multifocal ERG (mfERG), scanning laser ophthalmoscope microperimetry (SLO perimetry), fluorescein angiography, and Arden contrast color testing were performed in one male and three carriers. RESULTS: The findings in the affected male were typical for advanced choroideremia. The three carriers demonstrated a variable clinical phenotype including reduction of visual acuity and ERG and angiographic changes in one. Molecular genetic analysis revealed a functional null mutation (1388delCCinsG) in the REP-1 gene. CONCLUSIONS: A severe retinal pathology was found in the affected male, indicating that the 1388delCCinsG is a severe mutation. Varying phenotypes were present in the three carriers examined. The phenotype in carriers has been explained by random X-inactivation with varying expression of the inactivated and activated gene copy inside the same cell of both the retinal pigment epithelium and the rods. This thesis is in agreement with the clinical data obtained here.

Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best's disease.

PURPOSE: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. METHODS: Sixty-two healthy individuals and 12 patients with Best's disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (Infrared 730 nm). RESULTS: Amplitudes in the central concentric area were found to be significantly lower in patients with Best's disease than in healthy controls, while no significant differences were found for the more peripheral areas. CONCLUSION: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation.

Muscle surgery in patients with Graves' disease using topical anesthesia.

PURPOSE: To report our experience in extraocular muscle surgery for Graves' disease using topical anesthesia. DESIGN: Retrospective, noncomparative, observational case series. PARTICIPANTS: In 135 patients with Graves' disease, a total of 200 ocular muscles were operated during the past 20 years at the Department of Ophthalmology, Ludwig-Maximilian-University, Munich, Germany. METHODS: Surgery was performed under topical anesthesia with tetracaine hydrochloride 1% eyedrops. Because of the restrictive nature of the motility impairment, recession of the muscles was used in all patients. The exact amount of recession was determined during the operation with active cooperation from the patient. MAIN OUTCOME MEASURES: Binocular single vision and the angle of deviation were evaluated preoperatively and postoperatively. RESULTS: Postoperative binocular single vision in the primary position was achieved by 78.7% of the patients on the first postoperative day. Subsequent evaluation demonstrated binocular single vision in 91.9% of all patients and in 96.4% of the group with only 1 muscle (inferior rectus) operated. CONCLUSIONS: The authors have demonstrated that topical anesthesia is a feasible and reliable method for performing extraocular muscle surgery in patients with Graves' disease. Intraoperative patient discomfort seemed insignificant, and the active cooperation of the patient in finding the appropriate extent of surgery was advantageous. The overall results showed that deviation surgery with the use of topical anesthesia is highly successful in restoring binocular single vision in patients with endocrine orbitopathy.

[Mutations in the ABCA4 gene in a family with Stargardt's disease and retinitis pigmentosa (STGD1/RP19)]. / Mutationen im ABCA4-Gen in einer Familie mit Stargardtscher Erkrankung und Retinitis pigmentosa (STGD1/RP19).

BACKGROUND: Demonstrating the types of ABCA4 mutations in the STGD1 gene in a family manifesting both Stargardt's disease and retinitis pigmentosa (RP19). METHODS: Clinical ophthalmological examination included funduscopy, ERG, Arden Colour contrast test, fluorescein angiography in one patient, perimetry and SLO perimetry. The 50 exons of the ABCA4 gene were screened using a combination of denaturating gradient gel electrophoresis (DGGE), high performance electrophoresis (dHPLC) and SSCP analysis. RESULTS: Patient I/1 showed typical signs of Stargardt's disease, while her son, II-1 demonstrated functional signs and morphological features of retinitis pigmentosa. Mutational analysis of the ABCA4 gene revealed a missense mutation in exon 42 (G5882G > A) and a frameshift mutation in exon 43 (5917delG) of patient I-1. Patient II/1 demonstrated a homozygous 5917delG mutation in exon 43, resulting in a functional null-mutation. CONCLUSIONS: The combination of ABCA4 alleles with various functional consequences to protein activity can lead to different clinical phenotypes in one and the same family, resulting either in typical Stargardt's disease or in autosomal recessive retinitis pigmentosa (RP19).