The phenotypic spectrum in patients with arginine to cysteine mutations in the COL2A1 gene.

BACKGROUND: The majority of COL2A1 missense mutations are substitutions of obligatory glycine residues in the triple helical domain. Only a few non-glycine missense mutations have been reported and among these, the arginine to cysteine substitutions predominate. OBJECTIVE: To investigate in more detail the phenotype resulting from arginine to cysteine mutations in the COL2A1 gene. METHODS: The clinical and radiographic phenotype of all patients in whom an arginine to cysteine mutation in the COL2A1 gene was identified in our laboratory, was studied and correlated with the abnormal genotype. The COL2A1 genotyping involved DHPLC analysis with subsequent sequencing of the abnormal fragments. RESULTS: Six different mutations (R75C, R365C, R519C, R704C, R789C, R1076C) were found in 11 unrelated probands. Each mutation resulted in a rather constant and site-specific phenotype, but a perinatally lethal disorder was never observed. Spondyloarthropathy with normal stature and no ocular involvement were features of patients with the R75C, R519C, or R1076C mutation. Short third and/or fourth toes was a distinguishing feature of the R75C mutation and brachydactyly with enlarged finger joints a key feature of the R1076C substitution. Stickler dysplasia with brachydactyly was observed in patients with the R704C mutation. The R365C and R789C mutations resulted in classic Stickler dysplasia and spondyloepiphyseal dysplasia congenita (SEDC), respectively. CONCLUSIONS: Arginine to cysteine mutations are rather infrequent COL2A1 mutations which cause a spectrum of phenotypes including classic SEDC and Stickler dysplasia, but also some unusual entities that have not yet been recognised and described as type II collagenopathies.

Pronounced short stature in a girl with tricho-rhino-phalangeal syndrome II (TRPS II, Langer-Giedion syndrome) and growth hormone deficiency.

We report on a 10-year-old girl with tricho-rhino-phalangeal syndrome type II (TRPS II) and pronounced short stature (-4.8 SD). The patient has an interstitial chromosome 8q24.1 deletion of 12-15 Mb. The deletion spans all genes from CSMD3 to at least ANXA13 including the TRPS1 and EXT1 genes, which are responsible for the TRPS II phenotype. In addition to the features of TRPS II, the patient had growth hormone (GH) deficiency with diminished response in three stimulation tests. Therapy with 0.2 mg GH/kg/week led to an increase of growth velocity from 2.5 to 6.6 cm/year. To our knowledge, such a combination of TRPS II and GH deficiency has not yet been described.

Auxological, ophthalmological, neurological and MRI findings in 25 Austrian patients with septo-optic dysplasia (SOD). Preliminary data.

UNLABELLED: Septo-optic dysplasia (SOD) comprises ophthalmological, endocrinological and neurological disorders resulting from varying degrees of midline malformation of the forebrain like visual impairment by optic nerve hypoplasia, endocrine deficits due to hypothalamic and/or pituitary anomalies, and psychomental retardation by associated cortical malformation. MRI shows aplasia/hypoplasia of the septum pellucidum and corpus callosum as a radiological hallmark. For etiology, genetic defects (Hesx1/HESX1 gene) as well as vascular disruption during embryonic brain development are discussed. AIM: To perform detailed analysis of morphological findings and clinical symptoms and to improve care of SOD patients by interdisciplinary management. PATIENTS: We investigated 25 patients with a mean age of 5.1 years at diagnosis. RESULTS: Pituitary insufficiency was present in 11/25 patients, multiple deficits in 6 of them. Bilateral optic nerve hypoplasia was found in 70% of patients, unilateral in 20%. Mild or moderate neurological disorders were observed in the majority of patients (14/20), EEG was usually normal (12/19). Analysis of MRI films revealed very heterogeneous morphological anomalies, ranging from isolated agenesis of the septum pellucidum to multiple malformations, involving the cortex. Malrotation of the hippocampal structures was a common finding. CONCLUSION: We conclude that only interdisciplinary management of SOD patients can ameliorate the exact diagnosis and outcome, depending on early visual or developmental support as well as early diagnosis and substitution of potentially life-threatening endocrine deficits.

Cellular reaction on the anterior surface of 4 types of intraocular lenses.

PURPOSE: To assess the cellular reaction on the anterior surface of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. METHODS: One hundred eyes scheduled for cataract surgery were prospectively randomized into 4 groups of 25 eyes each using random number tables. Group 1 received a Hydroview IOL (Bausch & Lomb), Group 2 an AcrySof IOL (Alcon), Group 3 a MemoryLens IOL (ORC), and Group 4 a CeeOn 920 IOL (Pharmacia). Patients were examined 1, 3, 7, 30, 90, and 180 days postoperatively. Postoperative biomicroscopic examinations were done with a slitlamp, and a specular microscope was used to document the presence of cell deposits and identify areas with the highest density of cells. RESULTS: The local tissue response revealed 2 patterns: a nonspecific foreign-body reaction to the IOL (small round, fibroblast-like, epithelioid, and giant cells) and a lens epithelial cell (LEC) reaction. The highest incidence of LECs was in the Hydroview group, in which LECs were present on 81.8% of lenses 180 days postoperatively. During the first postoperative days, small round and fibroblast-like cells were found on all IOLs. From 7 days on, the incidence and density of these cells were less severe in the Hydroview and CeeOn 920 groups. After several weeks, epithelioid cells and foreign-body giant cells were seen on some IOLs. These cells appeared more often on AcrySof, MemoryLens, and CeeOn IOLs. CONCLUSION: This study found IOL-related differences in cellular reaction after cataract surgery. The incidence of a nonspecific foreign-body reaction to 4 IOLs is consistent with the results of previous studies. The incidence of LECs was highest in the Hydroview group and lowest in the AcrySof group. The CeeOn 920 group had the lowest incidence of all types of cells.

High-altitude retinopathy and retinal vascular dysregulation.

PURPOSE: (a) To show that high-altitude retinopathy (HAR) is common at high altitudes even in well-acclimatised climbers and that it should not be regarded as part of the spectrum of benign mountain sickness but rather as a clinical sign with a separate aetiology. (b) To test the hypothesis that HAR could be interpreted as a clinical expression of 'ocular vascular dysregulation'. METHODS: Both eyes of the 8 mountaineers of the First Vienna Himalayan Expedition in May/June 1996 were examined 2 weeks before departure to and 2 weeks after descent from a high altitude. Retinal blood flow was measured in the right eyes of 7 climbers, using the Heidelberg Retina Flowmeter (HRF). RESULTS: Two of the 8 climbers had bilateral retinal haemorrhage after the expedition. In 5 climbers chronic hypoxic exposure caused an increase in retinal blood flow between +18% and +96%, and in 2 climbers a decrease in retinal blood flow between -21% and -31%. The 2 climbers (climbers 1 and 2) with bilateral retinal haemorrhage showed a significant increase in HRF parameters. CONCLUSIONS: HAR may be a clinical sign of mountaineers with a tendency towards ocular vascular dysregulation. The pronounced increase in all haemodynamic parameters in the 2 climbers with retinal haemorrhage combined with a dilated epipapillary network 2 weeks after the exposure reflects a retinal vessel configuration, as might be expected at high altitudes under acute hypoxic stress. An inadequate autoregulatory response of the retinal circulation under conditions of chronic hypoxia may play an important part in the pathogenesis of HAR.

Long-term disorders of the blood-aqueous barrier after small-incision cataract surgery.

PURPOSE: To determine the long-term function of the blood-aqueous barrier after small-incision cataract surgery with implantation of a foldable intraocular lens. METHODS: The blood-aqueous barrier function in 74 eyes of 62 patients who underwent cataract surgery was examined using a laser flare-cell meter. The measurements were performed pre-operatively and post-operatively between 12 and 35 months after surgery. For statistical analysis a linear regression was used. The study was designed as a single cohort study, with comparison of pre- and post-operative values. RESULTS: Highly statistically significant differences (p < 0.0001) were found between pre-operative flare values and those measured at the final visit. The linear regression model showed significantly higher flare values post-operatively compared with those measured pre-operatively. Other variables such as incision technique, sex, operation time, phaco time and systemic disease had no influence on this outcome. CONCLUSION: The results suggest that there is persistent blood-aqueous barrier dysregulation even several years after cataract surgery.

Course of postoperative inflammation after implantation of 4 types of foldable intraocular lenses.

PURPOSE: To compare the course of postoperative inflammation after small incision cataract surgery with implantation of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Austria. METHODS: One hundred twenty eyes were prospectively randomized to receive a foldable silicone (Pharmacia 920), hydrogel (Bausch & Lomb Hydroview), methyl methacrylate/hydroxyethyl methacrylate (Mentor MemoryLens), or acrylic (Alcon AcrySof) IOL. All surgery was performed by the same experienced surgeon using a standardized surgical protocol: clear corneal incision, capsulorhexis, phacoemulsification, and in-the-bag implantation of the IOL. All patients received standardized postoperative medication and follow-up. Postoperative inflammation was evaluated by measuring aqueous flare preoperatively and 1, 3, 7, 14, 28, 90, and 180 days after surgery using the Kowa 1000 laser flare-cell meter. RESULTS: Except on the first day after surgery, when the AcrySof group had higher flare values than the other groups (P = .0265), no significant differences were found up to 6 months. Re-establishment of the blood-aqueous barrier was similar in eyes with the AcrySof, Hydroview, and MemoryLens IOLs; the course of postoperative inflammation was different in eyes with the silicone IOL. CONCLUSION: Comparison of postoperative flare values after implantation of 4 foldable IOLs showed no clinically relevant differences in the course of postoperative inflammation.