Michels syndrome: The first case report from India and review of literature

A 2-year 7-month-old girl born out of a consanguineous marriage, presented at our facility with clinical features characterized by the eyelid triad of blepharophimosis, blepharoptosis and epicanthus inversus in association with hypertelorism, cleft palate and craniosynostosis. This constellation of features is suggestive of Michels syndrome. At the time of writing this report, there were only ten reported cases worldwide and to the best of our knowledge, there have been no published reports from India.     

Ocular manifestation in GAPO syndrome. Report of the first tunisian case

GAPO syndrome is a rare autosomal recessive disorder whose main manifestations are: growth retardation, alopecia, pseudoanodontia and optic atrophy. We report here the ophthalmological findings in a 12-year-old Tunisian boy suffering from typical GAPO syndrome.     

Ocular manifestations in Kabuki syndrome: the first report from Saudi Arabia

Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome in which ophthalmological examination for the early detection of ocular abnormalities is desired in order to prevent visual impairment. Case: Retrospective, interventional, case report of a 5-year-old female patient of Arabic origin with features of Kabuki syndrome. Observation: Patient had neurological deficit, psychomotor retardation, a peculiar face, including large prominent cup shaped ears, broad depressed nasal tip, and high arched palate, and malformed teeth. Her ocular features suggestive of Kabuki syndrome included left upper eyelid congenital ptosis, lagophthalmos, arched eyebrows with temporal sparing of hair, long horizontal palpebral fissures, lateral lower eyelid eversion and resultant epiphora. Other abnormalities included medial lower epicanthal folds, abduction deficit bilaterally, large esotropia, significant hyperopia, right corneal opacity, iris and chorioretinal coloboma. Patient required hyperopic correction and ptosis surgery, which improved her visual functioning. Conclusions: We report the first case of a Kabuki syndrome patient from Saudi Arabia and stress on the importance of ophthalmological examination in all patients with KS for the early detection of ocular anomalies in order to prevent visual impairment.     

视屏终端综合征与干眼症关系的研究

目的:研究视屏终端综合征(visual display terminal,VDT)与干眼症的关系,并分析视屏操作时间对它的影响。方法:对符合干眼诊断标准的60例VDT患者进行问卷调查和眼科常规检查,作为可疑干眼的观察组,取年龄与之匹配的正常患者60例作为对照组,分别做基础泪液分泌试验(schimerⅠtest,SⅠt)、泪膜破裂时间检查(break uptime,BUT)、角膜荧光素染色(fluorescent,FL)、结膜细胞印迹学检查(impression cytology,IC),分析观察组的症状、病因进行分析。结果:观察组比对照组SⅠt试验,BUT,IC均显著降低,观察组症状的严重程度与每日VDT操作时间有显著性差异。结论:VDT是干眼的相关危险因素,且VDT的症状严重程度与VDT使用电脑时间相关。     

Retrobulbar neuritis as the first sign of the glucagonoma syndrome

A 63-year-old man with a metastasising pancreatic glucagonoma is described, who presented with progressive deterioration of vision and bilateral central scotomata as the first symptom. This patient was treated with dacarbazine (DTIC) 250 mg/m² IV daily for five consecutive days at 4-week intervals. The vision returned completely to normal, in a clinical and biochemical remission. Although there is no wide experience in treatment, the literature seems to indicate that DTIC should be the drug of choice in treating metastatic glucagonoma.Central scotomata may be a new paraneoplastic symptom and a key to the earlier diagnosis of the glucagonoma syndrome by ophthalmologists, just as necrolytic migratory erythema has been for the dermatologists.     

马凡综合征一家系的临床研究及致病基因连锁分析

目的研究一个中国人马凡综合征(Marfan sydrome,MFS)家系的临床特点,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个MFS家系,对家系所有成员进行全面详细的眼科及全身临床检查。确定其临床表型及遗传方式后,在位于MFS的已知基因FBN1、TGFBR1、TGFBR2附近选取微卫星标记物进行连锁分析。经ABI3130型遗传分析仪、Genscan2.1收集数据,Genotyper2.1进行基因分型,Link-age软件计算两点LOD值。结果该家系的遗传方式为常染色体显性遗传,家系中所有患者均具有典型的晶状体脱位、高度近视及MFS的特征性骨骼改变。仅有2例患者表现为心血管系统的异常。与该家系连锁的染色体微卫星标记物为D3S1609和D3S2432,其最大的LOD值为3.22。结论此家系为常染色体显性遗传型MFS,其致病基因位于3号染色体的D3S1609和D3S2432之间,位于该区间内的已知基因TGFBR2的突变可能是导致该家系致病的分子基础。     

Keratopathy in a family with the ectrodactyly-ectodermal dysplasia-clefting syndrome

Four members of a family with the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and associated keratopathy are presented. The main features of this syndrome include lobster-claw deformities of the hands and feet, abnormalities of the hair and teeth, cleft lip and palate, nasolacrimal abnormalities, and a progressive keratopathy ranging in severity from an asymptomatic pannus to bilateral dense corneal scarring and neovascularization. Despite congenital limb abnormalities, the major functional disability of three of these patients stems from severe photophobia and decreased visual acuity secondary to the corneal disease. Treatment with cycloplegics, topical steroids, and bandage soft contact lenses was unsuccessful. The EEC syndrome is transmitted in an autosomal dominant manner. The spectrum of keratopathy demonstrated in this family can be explained by the different ages of the patients, by variation in gene penetrance and expressivity and by differing durations and severity of dacryocystitis and related keratoconjunctivitis. The etiology of the keratopathy appears to be primarily a manifestation of the underlying ectodermal dysplasia with probable contributions from associated tearfilm abnormalities and external ocular infection.     

马凡综合征一家系的致病基因筛查

目的：对中国辽宁省一个具有常染色体显性遗传特点的马凡综合征( Marfan syndrole, MFS )家系进行突变基因的筛查。
　　方法：分别采集家系成员的外周静脉血,提取基因组DNA,通过对与马凡综合征相关的致病基因进行遗传学研究和分析,选取候选基因并设计引物,应用聚合酶链式反应( PCR)扩增DNA片段后进行琼脂糖凝胶电泳分离,利用直接测序法确定致病基因及其突变位点。
　　结果：该家系遗传方式符合常染色体显性遗传,先证者表型为双眼晶状体向鼻上方脱位,通过对候选基因外显子直接测序,发现该家系内患者原纤维蛋白基因-1(fibrillin-1 gene,FBN1)第7个外显子第640位碱基有1个A>G的点突变,此突变导致蛋白第214位的甘氨酸被丝氨酸取代(G214S)。
　　结论：FBN1基因 c. A640G(p. G214S)突变为该马凡综合征家系的致病因素。     

Osteoporosis-pseudoglioma syndrome: Report of two cases and a manifesting carrier

Background: Osteoporosis-pseudoglioma syndrome is a very rare disease mainly characterized by severe eye abnormalities and osteoporosis but also causing a broader range of clinical features. The syndrome is associated with homozygous or compound heterozygous variations in the LRP5 gene. In this report, we describe two children with a severe early-onset form of familial exudative vitreoretinopathy associated with skeletal abnormalities.

Materials and methods: Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination.

Results: In both probands, the diagnosis of osteoporosis-pseudoglioma syndrome was confirmed by detection of three new pathogenic LRP5 variants: p.(Asp379Asn), found in the homozygous state in one proband, and p.(Asp203Ala) in the compound heterozygous state with p.(Cys612Valfs*25) in the other. The clinical and genetic study was extended to their parents, confirming that heterozygous carriers may also have incomplete clinical manifestation of this syndrome.

Conclusions: To our knowledge, these are the first two cases of the syndrome described in Italy. Genetic testing proved to be fundamental for definition of the syndrome and confirms the importance of early detection of LRP5 variants for management of systemic features of the disease in patients and carrier relatives.     

A Chinese family with Axenfeld-Rieger syndrome: report of the clinical and genetic findings

AIM: To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome (ARS) and characterize the molecular defect in PITX2 in the family. METHODS: Patients presented with typical ARS from a Chinese family were investigated. We performed genome-wide linkage scan and exome sequencing to identify the pathogenic mutations. Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS: Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A>G substitution at position -11 of 3’ss of exon 5 (IVS5-11A>G) that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family. CONCLUSION: Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.     

青光眼与颈椎病的眼部表现特点关系探讨

目的:对一组症状,体征表现极相似于青光眼但非青光眼所致的颈椎病患者进行分析诊断,并作治疗探讨。方法:我院1993/2003-10间一组症状相似的颈椎病患者37例,分析其症状及体征特征,并与青光眼相鉴别。结果:通过此组患者症状体征分析,提醒相关医师掌握这些知识,对此组患者进行正确诊断和治疗。结论:该组患者是一组特殊类型的眼科患者,可暂称其为缺血性视疲劳。     

Association between metabolic syndrome and age-related cataract

AIM: To determine the effect of metabolic syndrome on age-related cataract formation.METHODS: We analyzed data for 2852 subjects [41.8% men and 58.2% women; mean (±SD) age, 52.9±13.9y], taken from the Korea National Health and Nutrition Examination Survey 2008. Metabolic syndrome was diagnosed by criteria proposed by the Joint Interim Societies. Cataract was diagnosed by using the Lens Opacities Classification System III. The association between metabolic syndrome and cataract was determined using age-adjusted and multivariable logistic regression analyses. RESULTS:In multivariable analyses, men with metabolic syndrome had a 64% increased risk of nuclear cataract [odds ratio (OR), 1.64; 95% confidence interval (CI), 1.12-2.39]. Women with metabolic syndrome had a 56% increased risk of cortical cataract (OR, 1.56; 95% CI, 1.06-2.30). Men and women with metabolic syndrome had a 46% (OR, 1.46; 95% CI, 1.01-2.12) and 49% (OR, 1.49; 95% CI, 1.07-2.08) increased risk of any cataract, respectively. The prevalence of nuclear and any cataract significantly increased with an increasing number of disturbed metabolic components in men, and prevalence of all types of cataracts increased in women. Men using hypoglycemic medication had an increased risk of nuclear (OR, 2.62; 95% CI, 1.41-4.86) and any (OR, 2.27; 95% CI, 1.14-4.51) cataract, and women using antidyslipidemia medication had an increased risk of cortical (OR, 2.18; 95% CI, 1.12-4.24) and any (OR, 2.21; 95% CI, 1.14-4.26) cataract.CONCLUSION: Metabolic syndrome and its components, such as abdominal obesity, high blood pressure, and impaired fasting glucose, are associated with age-related cataract formation in the Korean population.     

EEM syndrome: report of a family and results of a ten-year follow-up

We report on a Brazilian kindred in which two sibs presented with the complete form of EEM (ectodermal dysplasia, ectrodactyly, and macular dystrophy) syndrome with hypotrichosis, dental anomalies, syndactyly, and retinal changes with prominent pigmentation in the posterior pole of the retina. In this family, we also observed another sib with syndactyly, as well as a first cousin with ectrodactyly. A 10-year follow-up demonstrated gradually decreasing visual acuity and progression of retinal degenerative anomalies.     

A novel FBN1 missense mutation (p.C102Y) associated with ectopia lentis syndrome in a Chinese family

AIM:To characterize the disease-causing mutations in a Chinese family with ectopia lentis syndrome (ELS).METHODS:Patients and their family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA samples were extracted from the peripheral blood of the pedigree members and 100 healthy controls. Mutation screening was performed in the fibrillin-1 (FBN1) gene by bi-directional sequencing of the amplified products. The mutation was analyzed using two bioinformatics methods.RESULTS:A novel heterozygous c.305G>A mutation in exon 3 of FBN1 was detected. As a result of this change, a highly conserved cysteine residue was replaced by a tyrosine residue (p.C102Y). Another mutation was found in the same exon (c.303T>C), which did not change the amino acid sequence. Both mutations were discovered in each affected individual, but not in the unaffected family members, or in 100 ethnically matched controls. A bioinformatics analysis predicted that mutation p.C102Y would affect protein function.CONCLUSION:In the first epidermal growth factor-like module, we identified a novel FBN1 mutation (p.C102Y), which caused ELS in the family. Our study presented a unique phenotype, including some distinct ophthalmic findings, such as hypoplasia of the iris and anisometropia. Our results expanded the mutation spectrum of FBN1 and enriched the overall knowledge of genotype-phenotype correlations due to FBN1 mutations.     

An examination of the relationship between low vision and Charles Bonnet syndrome

Objective: In recent years, the Low Vision Clinic (LVC) appeared to have a large percentage of patients admitting to phantom vision (Charles Bonnet syndrome [CBS]). The objective of this study was to learn more about CBS from an ophthalmological perspective, as research has been conducted primarily by other specialists.Design: Large-scale prospective study using a cohort of low-vision and normal-vision subjects.Participants: Two hundred fifty-eight low-vision and 251 control subjects (with little or no vision loss) were enrolled.Methods: A comparison of visual acuity, ophthalmic conditions, eye treatments, medications, mental state, general health, socialization, etc., was undertaken, and other factors influencing the hallucinations were recorded.Results: CBS was present in 34% of LVC subjects and in <2% of the general population with little or no vision loss. Many subjects had unformed hallucinations; bright lights or spot-like images should not be overlooked because they could be determined to be hallucinations upon further questioning of the patient. CBS occurred in subjects with visual acuity from 20/40 to 20/1600; subjects were twice as likely to have CBS if their visual acuity was between 20/301 and 20/800.The prevalence of CBS did not differ significantly by cause of visual problem. Thirty-four percent of people were distressed about their initial hallucination; many did not consult a doctor for an explanation, and if they did, many did not receive an adequate explanation.Conclusions: This large-scale study shows that CBS is connected with a low vision level; thus, patients should be told about the common possibility of hallucinations.     

Usher综合征一家系的致病基因分析

目的：对一Usher综合征家系的临床特征进行分析,探索该家系的致病基因。

方法：收集于我院就诊的一视网膜色素变性家系,详细询问患者病史并进行临床检查,诊断为Usher综合征,抽取家系成员静脉血4mL,提取全基因组DNA,对先证者进行靶向捕获高通量测序获得突变位点,对于筛选出的可疑突变扩展至家系全体成员进行Sanger测序验证,同时在100名正常对照者中验证。

结果：患者除视网膜色素变性表现外,还存在轻至中度感音神经性耳聋,测序结果发现家系患者USH2A基因复合杂合突变c.2310_2311insA(p.E771Rfs*8)和c.8559-2A>G(IVS42),而在与患者有直系血缘关系的亲属中发现仅存在其中1个突变,其他家属成员和正常人中未发现该两种突变。

结论：USH2A基因为该家系的致病基因,c.8559-2A>G(IVS42)突变为已报道的热点突变,而c.2310_2311insA(p.E771Rfs*8)突变则为首次报道,本研究扩展了USH2A基因导致Usher综合征的突变谱。     

两个Usher综合征家系的临床表型分析及致病基因位点的初步定位

目的:分析2个Usher综合征家系USH-001,USH-002的临床表型特征及遗传学特点,对已知致病基因位点进行筛查,确定可能的候选基因。方法:分析USH-001,USH-002家系患者的临床表型特征、系谱特征,利用连锁分析的原理和方法,对12个已知致病基因位点周围的微卫星标记进行扫描,筛选可能的致病基因位点。结果:USH-001,USH-002家系中的患者在10～13岁出现夜盲症状,随年龄增长夜盲逐渐加重,并出现视野逐渐缩窄至管状视野,中心视力下降不明显,眼底周边见骨细胞样色素沉着;患者在儿童期出现双耳听力下降,为非渐进性、中-重度感音神经性耳聋,以高频听力损失为主,前庭功能正常。表型未出现连续遗传的现象。USH-001家系中所有患者的D11S902,D17S785微卫星标记的Allele值完全一致,USH-002家系所有患者的微卫星标记D1S425,D9S1776的Allele值完全一致。结论:USH-001,USH-002家系临床表现符合USH2型,为常染色体隐性遗传家系。USH1C,USH1G可能为USH-001家系的致病基因;USH2A,USH2D可能为USH-002家系的致病基因。     

Rare oculo-rhino-auditive variants of the branchial arch syndrome Report of three cases with two necropsy records

Different kinds of optic disc deformities are considered in this paper. These optic disc deformities include the tilted disc, the morning glory syndrome, the optic pit and the typical coloboma. All of these optic nerve deforrnities are probably typical and atypical optic disc colobomas. A clinical approach of these typical and atypical colomobas included different tests: angiography, electrophysiology and psychophysics. The genetic characteristics of these colobomas are considered.     

I型Stickler综合征家系临床和基因突变研究

背景Stickler综合征是一种遗传性结缔组织病,主要以眼部、关节、口面部及听力损伤为特征。确定Stickler综合征的基因突变位点能够为该综合征的基因诊断和治疗提供依据。目的研究一个I型Stickler综合征家系的临床特征并确定致病基因突变。方法对一个患I型Stickler综合征的家系进行临床研究和系谱分析。采集Stickler综合征家系中3例患者和6位表型正常者的外周血标本,采用PCR法扩增COL2A1基因的全部外显子及其侧翼,对扩增产物进行直接测序,结果与Genbank中相应序列进行比对。同时检测100位无亲缘关系的正常人外周血标本进行对照。结果该家系共4代11位成员,2位成员去世,其中包括1例患病者。现存的9位成员中共3例患者,调查显示该家系符合常染色显性遗传方式。3例患者的临床特点包括高度近视、膜型玻璃体异常及面中部扁平、短鼻、腭裂等,符合I型Stickler综合征的临床诊断。COL2A1基因突变筛查结果显示,该家系中3例患者COL2A1基因内含子12的第～个碱基发生了单个碱基缺失（IVSl2＋1Gde1）的杂合性剪接位点突变,核苷酸序列分析结果证实该突变致提前形成终止密码子,形成一种包括306个氨基酸在内的截短蛋白,导致该基因的功能异常,而家系中表型正常者及无亲缘关系的正常对照者均未发现该基因突变。结论本研究确定了一个I型Stickler家系,并在该家系确定了一个新的COL2A1基因突变,这是中国首次报道Stickler综合征家系的基因突变。