Subconjunctival Hemorrhage in a Child with the Blue Rubber Bleb Nevus Syndrome on Treatment with Oral Propranolol

Blue rubber bleb nevus syndrome (BRBNS) is a rare syndrome characterized by venous malformations of mostly skin and gastrointestinal tract. Patients present with multiple venous malformations in various organs including liver, spleen, heart, eye, and central nervous system. Few ophthalmological cases have been published in literature and at present, there are no clear guidelines on the treatment of eye hemorrhages associated with the BRBNS. We report a 3-year-old boy with the BRBNS who developed a spontaneous progressive enlarging subconjunctival hemorrhage in the left eye despite being treated with oral propranolol. The subconjunctival hemorrhage was caused by an underlying conjunctival vascular malformation. With topical treatment with timolol maleate 0.5% once a day in the affected eye, the lesion regressed completely after 4 months. This child represents the first case of the BRBNS associated with a subconjunctival progressive bleeding necessitating topical treatment despite oral propranolol effectively controlling the cutaneous lesions. We recommend ophthalmic screening of patients with BRBNS in early childhood. For patients with BRBNS-related subconjunctival vascular lesions with subsequent hemorrhage, treatment with a topical β-blocker may be an efficient and harmless treatment option

Clinically Relevant Response to Cisplatin-5-Fluorouracyl in Intestinal-Type Sinonasal Adenocarcinoma with Loss of Vision: A Case Report

A 68-year-old man presented with rapid progressive visual loss caused by a progressive local invasive sinonasal intestinal-type adenocarcinoma (ITAC) with intracranial invasion. The local relapse of ITAC in the ethmoid sinus was previously treated with palliative radiotherapy and carboplatin-paclitaxel, without response, hence disease progression was seen. Ophthalmological examination revealed irreversible blindness of the left eye and a dramatic progressive visual loss of the right eye. Due to important visual loss caused by optic nerve invasion, a palliative treatment with cisplatin-5-fluorouracyl was started. This therapy resulted in a good clinical response with a regression of the local mass and a partial recovery of the vision

Mutations in splicing factor genes are a major cause of autosomal dominant retinitis pigmentosa in Belgian families

Purpose : Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. Methods : Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. Results : Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5-30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). Conclusions : Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-associated adRP by the identification of 17 novel mutations

The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from diferent ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), fve of which are novel including a deletion spanning the 5′ untranslated region and the frst coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identifed in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the frst MFRP genomic rearrangement, ofering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO

No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome

BACKGROUND:Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seven patients have been described to carry a mutation in KIF11, which encodes a homotetrameric motor kinesin, EG5. METHODS: We tested 23 unreported MCLMR index patients for KIF11. We also reviewed the clinical phenotypes of all our patients as well as of those described in previously published studies. RESULTS: We identified 14 mutations, 12 of which are novel. We detected mutations in 12 affected individuals, from 6 out of 6 familial cases, and in 8 out of 17 sporadic patients. Phenotypic evaluation of patients (our 26+61 earlier published=87) revealed microcephaly in 91%, eye anomalies in 72%, intellectual disability in 67% and lymphedema in 47% of the patients. Unaffected carriers were rare (4 out of 87: 5%). Family history is not a requisite for diagnosis; 31% (16 out of 52) were de novo cases. CONCLUSIONS: All inherited cases, and 50% of sporadic cases of MCLMR are due to germline KIF11 mutations. It is possible that mosaic KIF11 mutations cause the remainder of sporadic cases, which the methods employed here were not designed to detect. On the other hand, some of them might have another mimicking disorder and genetic defect, as microcephaly is highly heterogeneous. In aggregate, KIF11 mutations likely cause the majority, if not all, of MCLMR

Retinopathy of prematurity in Rwanda: a prospective multi-centre study following introduction of screening and treatment services.

OBJECTIVES: To investigate risk factors for retinopathy of prematurity (ROP) in a newly established ROP screening and management programme in Rwanda, Africa. METHODS: In this multi-centre prospective study 795/2222 (36%) babies fulfilled the inclusion criteria (gestational age (GA)  30 weeks and BW > 1500 g, one of whom required treatment. In univariate analysis the following were associated with any ROP: increasing number of days on supplemental oxygen (OR 2.1, CI 1.5-3.0, P < 0.001), low GA (OR 3.4, CI 1.8-6.4, P < 0.001), low BW (OR 2.3, CI 1.5-3.4, P < 0.001), at least one episode of hyperglycaemia ≥ 150 mg/dl (OR 6.6, CI 2.0-21.5, P < 0.001), blood transfusion (OR 3.5, CI 1.6-7.4, P < 0.001) or sepsis (OR 3.2, CI 1.2-8.6, P = 0.01). In multivariate analysis longer exposure to supplemental oxygen (OR 2.1, CI 1.2-3.6, P = 0.01) and hyperglycaemia (OR 3.5, CI 1.0-12.4, P = 0.05) remained significant. CONCLUSIONS: ROP has become an emerging health problem in Rwanda, requiring programmes for screening and treatment. ROP screening is indicated beyond the 2013 American Academy guidelines. Improved quality of neonatal care, particularly oxygen delivery and monitoring is needed

Blau Syndrome-Associated Uveitis:Preliminary Results From an International Prospective Interventional Case Series

Purpose Provide baseline and preliminary follow-up results in a 5-year longitudinal study of Blau syndrome. Design Multicenter, prospective interventional case series. Methods Baseline data from 50 patients from 25 centers worldwide, and follow-up data for patients followed 1, 2, or 3 years at the end of study enrollment. Ophthalmic data were collected at baseline and yearly visits by means of a standardized collection form. Results Median age at onset of eye disease was 60 months and duration of eye disease at baseline 145 months. At baseline 38 patients (78%) had uveitis, which was bilateral in 37 (97%). Eight patients (21%) had moderate to severe visual impairment. Panuveitis was found in 38 eyes (51%), with characteristic multifocal choroidal infiltrates in 29 eyes (39%). Optic disc pallor in 9 eyes (12%) and peripapillary nodules in 9 eyes (12%) were the commonest signs of optic nerve involvement. Active anterior chamber inflammation was noted in 30 eyes (40%) at baseline and in 16 (34%), 17 (57%), and 11 (61%) eyes at 1, 2, and 3 years, respectively. Panuveitis was associated with longer disease duration. At baseline, 56 eyes (75%) were on topical corticosteroids. Twenty-six patients (68%) received a combination of systemic corticosteroids and immunomodulatory therapy. Conclusions Blau uveitis is characterized by progressive panuveitis with multifocal choroiditis, resulting in severe ocular morbidity despite continuous systemic and local immunomodulatory therapy. The frequency and severity of Blau uveitis highlight the need for close ophthalmologic surveillance as well as a search for more effective therapies

Exudative Type 3 Retinal Arteriovenous Malformation in a Pediatric Patient

We describe a 7-year-old girl who developed exudation nasally to the right optic disc due to retinal arteriovenous malformation. Fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography were performed. We give an overview of the different imaging techniques and discuss the differential diagnosis. Since there was no visual impairment, no treatment was started. A spontaneous decrease in edema and exudation was noted after 6 months