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Linkage of Autosomal Recessive Primary Congenital Glaucoma to the GLC3A Locus in Roms (Gypsies) from Slovakia

The autosomal recessive form of primary congenital glaucoma (gene symbol GLC3) has been recently mapped to two different loci, GLC3A (at 2p21), and GLC3B (at 1p36), respectively, on families of Turkish and Saudi Arabian provenance. This disorder is known to occur with an extremely high incidence in Roms (Gypsies) in Slovakia. We performed a standard linkage analysis on a sample of 7 Slovak Gypsy families comprising 18 affected members, and found significant linkage with four STR markers from the chromosomal region of 2p21 (D2S1788, D2S1346, D2S2328, and D2S1356), without heterogeneity. This finding demonstrates that in the Rom population of Slovakia, primary congenital glaucoma is due to the locus GLC3A, and consequently, to the mutation(s) in the cytochrome P4501B1 gene, which has been recently identified as the principal cause of the disease. Roms represent the third population, in which the disorder has been mapped to GLC3A.

GENETIC HETEROGENEITY OF CONGENITAL GLAUCOMA

Analysis of 126 families comprising 205 patients with congenital glaucoma demonstrates that in Gypsies this disease follows the pattern of autosomal recessive inheritance with complete penetrance, while in the non‐Gypsy population, its mode of inheritance is most probably multifactorial. In Gypsy patients with congenital glaucoma, the eyes are always bilaterally affected, the onset of the disease is in the prenatal period, and its course is rather severe. The population frequency of the disease is extremely high (among Gypsies), and the consanguinity rate among parents is as high as 41%. In non‐Gypsy patients, 26.6% of all cases are only unilaterally affected, and the course of the disease is generally milder with a later onset. The population frequency in a non‐Gypsy population is much lower, the consanguinity rate is not increased, and an excess of males (1.55:l) is significant.

Notes on the Genetics of Congenital Glaucoma

Relying on the analysis of 81 non-Gypsy families with congenital glaucoma from the entire territory of Slovakia, the authors discuss the share of the genetic component in the etiology of the disease. The characteristics of the families of this series resembled those of comparable series as far as the percentage of familial occurrence, the percentage of bilateral occurrence (73.56%), the percentage of parental consanguinity (4.87%) and in the prevalence of males with a ratio of 1.55:1 are concerned. The incidence of the disease in Slovakia varies around 1 per 22,000 live-born infants. In the non-Gypsy population of Slovakia, the authors assume a multifactorial etiology.

Ophthalmological Finding in the Patient with Lowe Syndrome

The authors present the ophthamological finding in a patient who at the age of 4.5 months was admitted due to a finding of total bilateral congenital cataract. The patient was observed by a neurologist for central hypotonia and mental retardation. Upon a complex examination of the patient, suspicion of Lowe syndrome was stated, which was confirmed by a metabolic examination and also by genetic tests. Upon an examination of the family, a genetic defect (mutation of OCRL1 gene) was confirmed also in the mother of the patient. A mild subcapsular opacification was present in the mother, beneath the posterior capsule. The patient was operated on for bilateral congenital cataract. Upon an examination under general anaesthesia, trabeculodysgenesis was diagnosed. Intraocular pressure remains within the norm. The patient is now aged 8 years, regularly monitored with regard to metabolic compensation, and by a neurologist and ophthalmologist, with satisfactory visual functions. Early diagnosis of the Lowe syndrome was determined on the basis of a complex examination of the patient within the framework of etiological diagnosis of bilateral congenital cataract. Key words: Lowe syndrome, oculo - cerebro - renal syndrome, congenital cataract, glaucoma, nystagmus.

Marshall and Stickler syndrome in one Family

The authors present the ocular finding in a patient sent to the Department of Paediatric Ophthalmology at the Childrens 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 childs mother had high myopia, the mothers brother underwent cataract surgery, the childs grandmother and her sisters and the childs great grandmother had high myopia and glaucoma, and probably underwent cataract surgery at a young age. The childs 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.

Cataract and early nystagmus due to galactokinase deficiency

Galactokinase deficiency (GALK-D, OMIM #230200) is a very rare autosomal recessive inherited disorder in the first step of galactose metabolism presenting as bilateral cataract. The highest incidence is found in Bulgaria and in Bosnia, primarily in the Romani population with prevalent founder mutation p.P28T (Hennermann et al 2011). Our patient was the son of healthy, Slovak, non-consanquineous and non-Romani parents. The mother noticed fixation instability of both eyes of her child at the age of 2 months and at 8 months the ophtalmologic investigation revealed nystagmus and bilateral cataract (Fig. 1). Biochemical analysis showed hypergalactosuria 5.38 mmol/mol/creat (reference values <0.38) and excessive high excretion of galactitol in urine 18,672 mmol/mol creat (reference values <90). Molecular analysis revealed two novel mutations in the GALK1 gene: p.M307del (c.919_921del1ATG) and p.M1V (c.1A>G), so the patient was diagnosed as a compound heterozygote for GALK-D. The patient had no other abnormalities, reported in GALK-D (Bosch et al 2002). Nystagmus is a known consequence of infantile cataract, but it has not been described in patients with GALK-D. Its presence may indicate a worse visual outcome for the reported child (Lambert et al 2006). This child underwent cataract surgery on both eyes without any significant complication.

Complex Multidisciplinary Follow-Up Of Children With Neurofibromatosis Type 1

Abstract Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders with mainly mild cutaneous manifestations. Some patients with NF1, however, develop severe complications such as progressive optic pathway glioma, plexiform neurofibroma or malignant peripheral nerve sheath tumour. Due to potentially progressive and asymptomatic course of the disease, patients with NF1 require a regular multidisciplinary follow-up in coordination with various specialties and early intervention. In this article, we summarise our long-term experience with multidisciplinary follow-up of NF1 patients in the Centre for Neurofibromatosis Type 1 patients at the Childrens University Hospital in Bratislava.

Scleral Reinforcement in Children with a Severe Myopia

The purpose of this study was to assess the influence of scleral reinforcement on the evolution of progressive severe myopia in children. Scleral. reinformcement after Thompson was performed on 182 eyes in 112 children from 3 to 18 years of the age.The main indications for surgery during 1992–1997 are the following: progressive myopia over — 7 diopters (untill 1995 over — 8 diopters), increase of refraction more than — 1 diopter per year. Porcine skin (Zenoderm) was used intraoperatively as alloplastic material in 91.8% patients. No serious complications were observed. The following results on a larger set of patients with a longer period of observation confirmed our previously published reports. Stabilisation was achieved up to 6 years after surgery in three important indicators of myopia: axial length in 76.7% of patients, refraction in 79.5% of infants and visual function in 78.6% of children. Scleral reinforcement is effective safe surgery that can stabilise the progression of severe myopia in children.

Long-Term Effectiveness of Scleral Reinforcement in Children with Difficult Progressive Myopia

The aim of this study was to assess the influence of scleral reinforcement on the evolution of difficult progressive myopia in children. Seventy-four eyes, in 51 children from 3 to 14 years old, were operated on for high myopia and then followed for 5 years. The main criteria for the operations were refraction above -8 D, an increase in the myopia of more than -1 D per year, and myopic signs on the fundus of the eye. Fascia lata and Zenoderm (Ethicon) were used peroperatively. No serious surgical complications were observed, and 5 years after the operations we found a stabilization of the axial length of the eye in 78% of patients and refraction in 85% of patients. Progression of the myopia was seen in 22% of children, but the average rate was -0.4 D per year compared with -1.1 D in a control set of 45 myopic children. Scleral reinforcement is the only known way to stop or retard the progression of difficult myopia in children, and is therefore recommended as a safe and effective operation.