Genetics in primary congenital glaucoma: Implications in disease management and counseling.

Primary congenital glaucoma is an important cause of visual impairment in children. It can develop both pre- and postnatally. Angle surgery is the first line treatment modality. If the disease remains untreated or if the diagnosis is delayed, it can lead to irreversible visual loss and blindness. The genetics of primary congenital glaucoma are complex and not yet entirely understood. At present multiple disease-causing genes have been identified. CYP1B1 is the most well known gene causing autosomal recessive congenital glaucoma. Other genes have been found to play a role through recessive, dominant or polygenic mechanisms. Here we provide an overview of the known genes and mechanisms described in patients with PCG. Furthermore, we provide a practical counseling and follow-up guideline for relatives of a proband.

Unilateral Coats'-like disease and an intragenic deletion in the TERC gene: A case report.

We report a case of a 25-year-old woman with unilateral Coats'-like disease. Her brother was previously diagnosed with an autosomal dominant form of dyskeratosis congenita. Genetic testing was performed by screening the TERC gene for mutations and identified heterozygosity for the n.68_124del mutation. Our case demonstrates that the exudative retinopathy seen in Coats'-like disease can be caused by mutations in a telomere-capping gene TERC as a part of the dyskeratosis congenita spectrum without other systemic involvement. This is an interesting case that illustrates that retinal Coats'-like involvement can be the first manifestation of dyskeratosis congenita.

Choroidal abnormalities in café-au-lait syndromes: a new differential diagnostic tool?

The best known café-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café-au-lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty-four patients with NF1 (14 with a truncating mutation, 14 with a non-truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non-truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow-up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.

Posterior amorphous corneal dystrophy caused by a de novo deletion.

We present a newborn diagnosed with posterior amorphous corneal dystrophy (PACD). PACD is a rare disorder with partial or complete posterior lamellar corneal opacification. Genetic screening showed a deletion of chromosome 12q21.33-q22 containing the identified four small leucine-rich proteoglycans (SLRP's) associated with this particular dystrophy. Neither parents were carrier of the deletion. To our knowledge, this is the first report of a de novo mutation causing PACD.

Comparative study of the ophthalmological examinations in neurofibromatosis type 1. Proposal for a new screening algorithm.

PURPOSE: Efforts are made to unify the protocol concerning the ophthalmological screening, monitoring and treatment of Optic Pathway Gliomas (OPGs) in children with neurofibromatosis type 1 (NF1). The aim of this study is to compare the most recent recommendations published in 2007 with the screening strategies in NF1 centres. The integration of these data resulted into a recommendation for an improved screening strategy. METHODS: A literature search on PubMed between 1984 and 2013 was performed. A questionnaire on the ophthalmological screening in NF1 was sent to centres of expertise in the field of NF1. Literature and questionnaire data were analysed. Also, findings of a round table discussion on the ophthalmological screening of NF1 patients at the European Paediatric Ophthalmological Society (EPOS) meeting in 2013 were summarized. RESULTS: In most centres ophthalmological screening in NF1 patients is well organized, but is performed longer and at more regular intervals than is mentioned in the recommendations. Visual acuity testing, fundoscopy and pupillary reflexes are carried out unanimously. CONCLUSIONS: There is no uniformity of the ophthalmological screening in NF1 patients. The present recommendation advises to screen annually until the age of 8. Because OPGs are likely to develop before the age of 6 and children do not usually complain of visual problems, OPGs can be missed or detection can be delayed if screening is only yearly performed at this young age. Based on these arguments, about half of our responders screen more frequently and until a later age. Therefore, we suggest performing a six monthly screening until the age of 6 and a yearly examination from 6 years until adulthood. This examination should include visual acuity assessment, pupillary reflexes and a fundoscopy.

Role of visual evoked potentials in the assessment and management of optic pathway gliomas in children.

OBJECTIVE: The aim of this study is to investigate the role of pattern reversal visual evoked potentials (pVEPs) in the screening and monitoring of optic pathway gliomas (OPGs) in children with and without neurofibromatosis type 1. METHODS: A review of the English literature published between 1980 and 2012 was performed, with comparison of results of retro- and prospective studies. RESULTS: Pattern reversal VEPs have a high sensitivity (85.7-100 %) for the diagnosis of OPGs, moreover they are safe and cost-effective. Conversely, they have a low specificity (43-83 %) and are not widely available. Besides, pattern reversal VEP results can be unreliable in young children, because of the need for a good cooperation. The studies that were analyzed have drawbacks, including the small sample size, the retrospective design, the differences in gold standard for diagnosis, the different interpretation of small changes in VEP results and the lack of control groups. CONCLUSION: There is still debate about the gold standard for the screening and follow-up of OPGs. The added value of pVEPs to the ophthalmic examination is controversial. Randomized controlled trials or prospective multicentre studies are necessary to assess with sufficient accuracy the sensitivity and specificity of pattern reversal VEPs in the screening for OPGs and its follow-up.