The authors present the ocular finding in a patient sent to the Department of Paediatric Ophthalmology at the Children's University Hospital - Faculty of Medicine, Comenius University in Bratislava at the age of 3 months, with congenital glaucoma in her right eye and bilateral high myopia. The family anamnesis of the patient shows repeated occurrence of stunted growth, myopia, facial dysmorphia and cataract. The child's mother had high myopia, the mother's brother underwent cataract surgery, the child's grandmother and her sisters and the child's great grandmother had high myopia and glaucoma, and probably underwent cataract surgery at a young age. The child's mother and grandmother underwent a genetic examination, with a conclusion of Marshall syndrome. Within the framework of neonatal screening, poor cortical auditory evoked potential, a defect of the interventricular septum and bifid uvula were diagnosed in the child. With regard to the overall finding in the patient and the genetic family history, we suspected Marshall syndrome. A genetic examination determined Stickler syndrome type 1 with the presence of mutation in the COL2A gene (variant c.2710C >T (p.Arg904Cys,rs121912882)). Due to high intraocular pressure with the impossibility of compensation by medication, bilateral trabuculectomy was performed on the patient. At present the patient has intraocular pressure compensated with adjuvant medicamentous therapy. With regard to high myopia and pronounced degenerative changes on the periphery of the retina in the sense of lattice degeneration, preventive cryopexy of the retinal periphery is planned. A molecular genetic analysis helped diagnose the pathology as Stickler syndrome type 1, which manifested phenotype symptoms of Marshall syndrome or Stickler syndrome type 2. Key words: Marshall syndrome, Stickler syndrome, mid-facial dysmorfism, myopia, glaucoma, cataract.

• Klíčová slova
• Marshall syndrome, Stickler syndrome, cataract, glaucoma, mid-facial dysmorfism, myopia,
• MeSH
• artritida * diagnóza   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• myopie MeSH
• nemoci pojiva * diagnóza   genetika   MeSH
• odchlípení sítnice * diagnóza   genetika   MeSH
• percepční nedoslýchavost * diagnóza   genetika   MeSH
• rodokmen MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Stickler syndrome (STL) is an inherited progressive connective tissue collagen disorder. STL is the most common hereditary cause of retinal complications, retinal tears, and the development of retinal detachment (RD) in childhood. The aim of the study was to evaluate the long-term anatomical and functional results of surgical treatment of retinal complications in children and adolescents affected by STL. METHODS: A retrospective, single-center study was performed a cohort of children with STL who underwent retinal surgery between 2004 and 2021. RESULTS: The study group consisted of nine children; the mean age at the time of the retinal tear with/without retinal detachment was 7.2 (2-10) years, and the mean follow-up period was 9.6 (5-16) years. Pathogenic variants COL2A1 (5 children) and COL11A1 (3 children) were confirmed in our cohort. In total, we operated on 13 eyes, 11 eyes with complicated RD and two eyes with multiple retinal defects, but without RD. At the end of the follow-up period, an attached retina was achieved 77% (10 eyes) with or without silicone oil tamponade: cryopexy alone was successful in one eye (10%), scleral buckling (EB) in five eyes (50%), and vitrectomy with silicone oil tamponade combined with EB in four eyes (40%). The mean number of surgeries was 2.3 per eye. The resulting best corrected visual acuity ranged from 0.03 to 0.1 in one eye, from 0.16 to 0.4 in two eyes, and from 0.5 to 1.0 in 7 eyes. CONCLUSION: Repair of retinal tears with/without retinal detachment in patients with Stickler syndrome often requires multiple surgeries with combinations of cryopexy, scleral buckling, and/or vitrectomy with silicone oil tamponade. Treatment of the ocular complications arising from STL requires long-term comprehensive care.

• Klíčová slova
• COL11A1, COL2A1, Child, Retinal complication, Retinal detachment, Retinal surgery, Stickler syndrome,
• MeSH
• artritida MeSH
• bukláž skléry MeSH
• dědičné nemoci očí * chirurgie   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• nemoci pojiva MeSH
• odchlípení sítnice * diagnóza   etiologie   chirurgie   MeSH
• percepční nedoslýchavost MeSH
• perforace sítnice * chirurgie   MeSH
• retina patologie   MeSH
• retrospektivní studie MeSH
• silikonové oleje MeSH
• vitrektomie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• silikonové oleje MeSH

We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.

• Klíčová slova
• COL11A1, COL2A1, Marshall syndrome, Stickler syndrome, myopia, nonsyndromic hearing loss, retinal detachment,
• MeSH
• artritida genetika   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• kojenec MeSH
• kolagen typ II genetika   MeSH
• kolagen typ XI genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutační analýza DNA MeSH
• nemoci pojiva genetika   MeSH
• odchlípení sítnice genetika   MeSH
• percepční nedoslýchavost genetika   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• COL11A1 protein, human MeSH Prohlížeč
• COL2A1 protein, human MeSH Prohlížeč
• kolagen typ II MeSH
• kolagen typ XI MeSH

AIMS: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. METHODS: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. RESULTS: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. CONCLUSION: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis.

• Klíčová slova
• ZNF469, blindness, brittle cornea syndrome, corneal rupture, deafness, penetrating keratoplasty,
• MeSH
• abnormality očí diagnóza   genetika   patofyziologie   MeSH
• artritida diagnóza   MeSH
• chybná diagnóza MeSH
• dospělí MeSH
• edém rohovky patofyziologie   chirurgie   MeSH
• glaukom patofyziologie   chirurgie   MeSH
• heterozygot MeSH
• keratoplastika perforující MeSH
• kožní abnormality diagnóza   genetika   patofyziologie   MeSH
• lidé MeSH
• myopie patofyziologie   MeSH
• nemoci pojiva diagnóza   MeSH
• nestabilita kloubu vrozené   diagnóza   genetika   patofyziologie   MeSH
• odchlípení sítnice diagnóza   patofyziologie   chirurgie   MeSH
• percepční nedoslýchavost diagnóza   MeSH
• perforace rohovky patofyziologie   chirurgie   MeSH
• reoperace MeSH
• trabekulektomie MeSH
• transkripční faktory genetika   MeSH
• vitrektomie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• transkripční faktory MeSH
• ZNF469 protein, human MeSH Prohlížeč

OBJECTIVE: Stickler's syndrome (SS) is an autosomal dominant hereditary disease of the collagenous connective tissue where impaired development of the vitreous body gel and peripheral retina and detachment of the retina are associated with general manifestations. The objective of the retrospective study was to evaluate the long-term results of surgery of retinal detachment in SS. PATIENTS: The group of patients comprised 7 patients, 6 men and 1 woman aged 4 to 45 years, average age 16.8 years. Autosomal dominant heredity was obvious in 6 members (85.7%) of two families. General manifestations of SS included abnormalities of the facial skeleton (6 patients), cleft palate (4 patients), impaired hearing (2 patients), marfanoid habitus (2 patients) and hyperextensibility of the joints (4 patients). In the eyes with SS was manifested by myopia from -1 to -9 D and a liquid vitreous body. Multiple foci of lattice degeneration supplemented the finding in 6 patients (85.7%). Detachment of the retina was a manifestation of SS in 12 of 14 eyes (85.7%). It was manifested in 5 of 7 patients concurrently or within 12 years in both eyes. The causes of retinal detachment were multiple equatorial and postequatorial tears due to lattice degeneration in 8 eyes (66.7%) or a giant tear in 4 eyes (33.3%). Advanced proliferative vitreoretinopathy (PVR) was associated with retinal detachment in 8 eyes (66.7%) and in 6 eyes (50%) it was not possible to assess the beginning of retinal detachment. RESULTS: In 3 of 5 patients with bilateral retinal detachment the adverse course of retinal detachment on the first eye was followed 8 to 12 years previously in another department: two retinal detachments with giant tears were evaluated as inoperable and one inveterated detachment with advanced PVR was operated unsuccessfully. Retinal detachment was operated in 9 eyes of 7 patients, in two patients both eyes were operated simultaneously. The patients were followed up after surgery for 11 months to 15 years, on average for 65 months. A cryosurgical approach was used in 6 retinal detachments (66.7%), accentuated cerclage with drainage of subretinal fluid in 5 and radial plombage in one eye. The retina attached in 5 of 6 eyes (83.3%) and the final visual acuity was 0.25-0.1, mean 0.66. Pars plana vitrectomy (PPV) and implantation of silicone oil (ISO) were the final surgical solution in 3 eyes of 3 patients (33.3%). In one eye with retinal detachment with a circumferential width of 320 degrees and advanced PVR PPV and ISO were the primary operation, in two eyes re-operation on account of a relapse of retinal detachment with advanced PVR after an unsuccessful cryosurgical operation. Anatomical and functional success was achieved in 2 of 3 eyes (66.7%), in one eye after removal of silicone oil from the eye. The final visual acuity of successfully operated eyes was 0.2 and 0.16. CONCLUSIONS: Retinal detachment in SS usually affects both eyes, the second eye may be affected after many years. The cause of retinal detachment are multiple tears or a giant tear. Early surgery of retinal detachment has as a rule a favourable effect, while late diagnosis of retinal detachment in children leads frequently to blindness. Dispensarization and regular ophthalmological check-ups of patients with SS are an essential prerequisite of successful prevention and treatment of retinal detachment.

• MeSH
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mnohočetné abnormality * MeSH
• odchlípení sítnice genetika   chirurgie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH