Peters异常PITX2及PAX6基因型表型分析

目的：分析中国人Peters异常(PA)患者的临床特征,研究Peters异常患者PITX2及PAX6基因变异情况。

方法：选取2016/2019年在常州市第二人民医院及第三人民医院眼科就诊的15例Peters异常患者,并收集详细的相关临床资料。征得患者及其家系成员的同意后抽血制备基因组DNA,用聚合酶链反应(PCR)对致病基因PITX2及PAX6的编码区及其临接内含子进行扩增后,直接测序筛查中国人群Peters异常患者PITX2及PAX6基因变异,异源双链-单链构象多态性分析(HA-SSCP)的方法对突变患者及其家系成员及80例正常对照进行验证; 分析比较国内已报道的Peters异常患者PITX2及PAX6基因突变并研究其相关表型。

结果：Peters异常患者15例PITX2基因突变筛查结果发现了1种新PITX2的突变c.296delG(P.R99fsx56),导致该基因的功能异常,分析突变患者临床特征,该患者右眼诊断为Axenfeld-Rieger综合征(ARS),左眼诊断为Peters异常。而家系成员中该患者父母及无亲缘关系的正常对照者均未发现相同突变,故此突变为新生突变。PAX6基因突变筛查未能发现突变。

结论：PA患者15例中检测到1个新PITX2基因突变,丰富了PITX2基因突变频谱,进一步明确了PA合并ARS眼病的临床特点,为该种少见眼病的临床诊断和发病原因提供了依据。     

Congenital Corneal Opacities: A Review with a Focus on Genetics

Congenital corneal opacities present in approximately 3/100,000 newborns. Many different disorders may result in corneal opacifications of infancy, including Peters' anomaly (PA), congenital hereditary endothelial dystrophy (CHED), congenital hereditary stromal dystrophy (CHSD) and posterior polymorphous dystrophy (PPMD). Current studies have localized defects using genetic testing in PA, CHED, CHSD and PPMD. Identifying mutations for specific disorders may lead to better understanding of the underlying pathogeneses and may help with diagnosis and prognosis. This article will review the clinical presentations, treatments and genetics of Peters' anomaly, congenital hereditary endothelial dystrophy, congenital hereditary stromal dystrophy and posterior polymorphous dystrophy.     

Unilateral Peters' anomaly with chorioretinal coloboma in the other eye

An 18-year-old man presented with poor vision in both eyes that had been present since birth. Central corneal opacity and inferior peripheral sclerocornea with iridocorneal adhesion were observed upon anterior segment examination of the left eye. A coloboma of the iris was observed in the patient's right eye, which manifested as a small notch in the inferior pupillary margin and cataract. Fundus examination of the right eye showed a large inferior chorioretinal coloboma involving the optic disc and macula. It is essential to examine the fundus in detail, if possible, in cases of Peters' anomaly, because these patients may have congenital anomalies such as chorioretinal coloboma.     

Corneoscleral transplantation in congenital corneal staphyloma and Peters' anomaly

An infant born with bilateral corneal clouding diagnosed clinically as congenital anterior staphyloma and Peters' anomaly was confirmed histopathologically. This case report demonstrates one clinical spectrum of Peters' anomaly. The clinical course and histopathologic findings are detailed as is a unique surgical approach of corneoscleral graft used to perserve the right globe.     

Anterior Segment and Retinal Pigmentary Abnormalities in Arteriohepatic Dysplasia

Arteriohepatic dysplasia (AHD, Alagille's syndrome) is presumed to be one of the six known familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. Accurate early diagnosis of the proper syndrome is important, as arteriohepatic dysplasia has a good prognosis, whereas the other syndromes usually lead to death in infancy or early adulthood. Posterior embryotoxon was found in all five of our patients and may be one of the hallmarks of this syndrome. Axenfeld's anomaly was present in three of five patients, and retinal pigmentary abnormalities were found in four of five patients. Variable abnormalities were found in the cardiovascular system, bones, central nervous system, kidneys, endocrine system, and body habitus. Inheritance may be autosomal dominant as vertical transmission was documented in one family. Liver function improves during the first five years of life so that only the ocular and skeletal signs may be present in adults.     

Axenfeld-Rieger syndrome. A spectrum of developmental disorders

The clinical and histopathologic features of Axenfeld's anomaly and Rieger's anomaly and syndrome are reviewed, and recent findings regarding the pathogenesis of this spectrum of developmental disorders are discussed. Based on these observations, it has been suggested that a developmental arrest, in the third trimester of gestation, of tissues derived from the neural crest cells accounts for the ocular and most of the nonocular abnormalities in this group of disorders. Since previous collective terms, such as mesodermal dysgenesis and anterior chamber cleavage syndrome, are not consistent with these new observations, the alternative name, Axenfeld-Rieger syndrome, has been proposed. The differential diagnosis of the syndrome includes two additional spectra of disorders: the iridocorneal endothelial syndrome and the posterior polymorphous dystrophies. The most serious ocular problem in Axenfeld-Rieger syndrome is the associated glaucoma, which occurs in a high percentage of patients and is typically difficult to control. Recent observations regarding the mechanism of the glaucoma, as reviewed in this paper, provide guidance in the management of this aspect of Axenfeld-Rieger syndrome.     

Bilateral Complete Isolated Cryptophthalmos: A Case Report

Cryptophthalmos is a condition of congenital eyelid malformation most commonly accompanied by syndactyly, urogenital anomalies, and cognitive impairments as in Fraser syndrome. We report on a patient with characteristic features consistent with autosomal dominant bilateral complete isolated cryptophthalmos. This patient represents only the sixth documented case of bilateral complete isolated cryptophthalmos. Defining characteristics of this variety are discussed, including bilateral central dimpling over the globes, normal eyebrow growth, and the absence of cognitive impairment. We introduce phenotypic features that distinguish bilateral isolated cryptophthalmos from other forms and discuss its relatively favorable prognosis.     

Posterior embryotoxon: its epidemiology and significance as a sign of glaucoma

Background: Posterior embryotoxon (PET) forms part of a spectrum of anterior chamber developmental anomalies, several of which are risk factors for glaucoma. Posterior embryotoxon also occurs as an isolated anomaly. This study was undertaken to determine the prevalence of PET and whether PET in isolation is a risk factor for glaucoma. Methods: Consecutive patients were examined for PET and their intraocular pressures recorded. Consecutively presenting patients having glaucoma were also examined for PET. All patients having PET or glaucoma were further examined by gonioscopy for evidence of other anterior chamber developmental anomalies. Results: PET occured in 47 (6.1 per cent) of 765 patients. There was no statistically significant difference between the intraocular pressure of patients having PET and those who did not. Patients having glaucoma did not have higher prevalence of PET than normals. Axenfeld's anomaly occurred in four of the non-glaucoma PET patients and in one of the glaucoma patients. Conclusions:PET in isolation does not appear to be a risk factor for glaucoma but might be an appropriate indication for gonioscopy. (Clin Exp Optom 1995; 78: 2: 74–78)     

A novel nonsense B3GALTL mutation confirms Peters plus syndrome in a patient with multiple malformations and Peters anomaly

Peters plus syndrome is an autosomal recessive rare congenital disorder defined by corneal Peters anomaly with short disproportionate stature, development delay and dysmorphic facial features. In addition, cardiac, genito-urinary and/or central nervous system malformations can be present. Mutations in the beta-1,3-galactosyltransferase-like glycosyltransferase gene (B3GALTL) have been reported in patients with Peters plus syndrome prompting phenotype-genotype studies because of the variable clinical spectrum related to the syndrome. A 20 month old boy presenting with bilateral Peters anomaly in association with multiple developmental anomalies including cerebral malformations was found to carry a novel homozygous B3GALTL nonsense mutation [p.Tyr366X]. This is the first stop mutation described in association with this gene. The present report confirms the wide clinical spectrum of Peters plus syndrome, underlines the major clinical criteria of the syndrome and the major implication of B3GALTL gene in this condition. Ophthalmologic examination in multiple developmental anomalies remains an important clinical issue that may lead to specific gene screening. In Peters plus syndrome B3GALTL molecular test provides diagnosis confirmation and improves dramatically genetic counselling for the families.     

Stickler's syndrome associated with congenital glaucoma

A case report of Stickler's syndrome associated with congenital glaucoma is presented. Stickler's syndrome is an autosomal dominant disorder characterised by progressive arthropathy, midfacial flattening, Pierre Robin anomaly or cleft palate, sensorineural hearing loss, progressive myopia, vitreoretinal degeneration, and retinal detachment. Congenital glaucoma and Stickler's syndrome are two diagnoses frequently considered in high myopia in infancy. The case report described presents a case of Stickler's syndrome in association with congenital glaucoma. This association is unusual, but important to recognise in the neonatal period. The possibility of coexistence of these clinical entities should be considered in the future.     

Evaluation of a simple photographic technique to detect pupillary dilation lag due to Horner's syndrome

Objective: Properly timed photographs of the pupils is one technique to demonstrate delayed pupillary dilation, called dilation lag, that is present in patients with unilateral Horner's syndrome. We utilized this technique to evaluate the amount of dilation lag that could distinguish Horner's syndrome. Methods: Fifty-six patients with Horner's syndrome and 39 normal subjects (with physiologic anisocoria ranging from 0.0 to 0.5 mm) had Polaroid photographs taken of both pupils simultaneously under three conditions: at baseline (room light), after five seconds of darkness, and after 15 seconds of darkness. For this study, pupillary dilation lag was operationally defined as the difference in anisocoria between five seconds and 15 seconds of darkness. Results: The median dilation lag was 0.1 mm (range: 0.0–0.3 mm) in normal subjects and 0.3 mm (range: 0.0–1.6 mm) in Horner's patients. A dilation lag of 0.4 mm or more was 100% specific for differentiating Horner's syndrome from physiologic anisocoria, but the sensitivity was 48%. There was no significant correlation between the magnitude of the baseline anisocoria and the amount of dilation lag nor between the amount of dilation lag and postcocaine anisocoria. Conclusions: This photographic technique is a simple and readily available nonpharmacologic method to detect pupillary dilation lag and confirm unilateral Horner's syndrome. However, not all Horner's patients demonstrate a significant amount of dilation lag. Thus, the absence of dilation lag (less than 0.4 mm) does not rule out Horner's syndrome and, in suspected cases, cocaine testing is recommended.     

The ‘morning glory’ syndrome

This paper discusses the characteristic features of ‘morning glory’ syndrome, observed in 49 patients, described in the literature and in three personal observations. ‘Morning glory’ syndrome is frequently associated with strabismus (20/49 patients), non-rhegmatogenous retinal detachment (13/56 eyes) or remnants of the hyaloid system (10/56 eyes). Association with basal encephalocele has been encountered three times. The ‘morning glory’ syndrome usually affects only one eye, although four bilateral cases have been described. The family history was negative, except in the cases discussed by Handmann (1929) and by Rieger (1977), where father and son presented the optic disc anomaly. In Rieger's family there was also familial renal hypoplasia. Morning glory syndrome is not to be considered as a true coloboma, but rather as a posterior ectasia, due to disturbance in the development of the sclera.     

Does Horner's syndrome in infancy require investigation?

AIMS—To evaluate whether isolated Horner's syndrome presenting in the first year of life warrants investigation.
METHOD—Retrospective review of 23 children presenting with Horner's syndrome in the first year of life.
RESULTS—In 16 patients (70%) no cause was identified. Birth trauma was the most common identifiable cause (four patients). Twenty one children (91%) had urinary vanillylmandelic acid (VMA) measured and 13 patients (57%) underwent either computed tomography or magnetic resonance imaging of the chest and neck. These investigations revealed previously undisclosed pathology in only two—one ganglioneuroma of the left pulmonary apex and one cervical neuroblastoma. A further patient was known to have abdominal neuroblastoma before presenting with Horner's syndrome. There were no cases of Horner's syndrome occurring after cardiothoracic surgery. Long term follow up of the patients (mean 9.3 years) has not revealed further pathology.
CONCLUSIONS—Routine diagnostic imaging of isolated Horner's syndrome in infancy is unnecessary. Infants should be examined for cervical or abdominal masses and involvement of other cranial nerves. If the Horner's syndrome is truly isolated then urinary VMA levels and follow up in conjunction with a paediatrician should detect any cases associated with neuroblastoma. Further investigation is warranted if the Horner's syndrome is acquired or associated with other signs such as increasing heterochromia, a cervical mass, or cranial nerve palsies.

Keywords: Horner's syndrome; neuroblastoma     

Congenital ectropion uveae with glaucoma

Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, often associated with neurofibromatosis and occasionally with other ocular anomalies. We present eight patients with unilateral CEU. Seven patients had glaucoma in the involved eye, while the eighth was a 10-week-old infant. In the two patients with bilateral glaucoma, the second eye was similar to the first, but without CEU. Three patients had neurofibromatosis, two had facial hemihypertrophy, one had Rieger's anomaly, one had Prader-Willi syndrome, and one had no systemic anomalies. Two had initially been misdiagnosed as having a large pupil in the involved eye and one as having a Horner's syndrome in the uninvolved eye. The finding of CEU in an infant warrants continued observation for the development of glaucoma and disorders of neural crest origin.     

Wildervanck syndrome associated with cleft palate and short stature

We report a case of Wildervanck syndrome exhibiting Klippel-Feil anomaly, Duane retraction syndrome and deafness. Since the first case was reported in 1952, there have been more reports describing this triad, either complete or incomplete. Our patient had the complete triad of the syndrome along with cleft palate and short stature. Also, a review of the literature regarding this syndrome is presented here.     

Adult Horner's syndrome: a combined clinical,pharmacological, and imaging algorithm

The diagnosis of Horner''s syndrome (HS) can be difficult, as patients rarely present with the classic triad of ptosis, miosis, and anhydrosis. Frequently, there are no associated symptoms to help determine or localise the underlying pathology. The onset of anisocoria may also be uncertain, with many cases referred after incidental discovery on routine optometric assessment. Although the textbooks discuss the use of cocaine, apraclonidine, and hydroxyamphetamine to diagnose and localise HS, in addition to reported false positive and negative results, these pharmacological agents are rarely available during acute assessment or in general ophthalmic departments. Typically, a week is required between using cocaine or apraclonidine for diagnosis and localisation of HS with hydroxyamphetamine, leaving the clinician with the decision of which investigations to request and with what urgency. Modern imaging modalities have advanced significantly and become more readily available since many of the established management algorithms were written. We thus propose a practical and safe combined clinical and radiological diagnostic protocol for HS that can be applied in most clinical settings.     

用循证医学方法分析我国Vogt-小柳-原田综合征的特点

Vogt-小柳-原田综合征是一种常见的疾病。我们对42篇文献(含1589例)进行分析整理,结果本病发病年龄8～76(平均36.03)岁。男835例,女736例。双眼同时或先后发病1585例,4例为单眼发病。发病时视力半数<0.2,也有少部分接近正常。眼外损害以头痛最常见,约为67%,耳鸣和脱发的发生率分别为39%和33%。也有相当部分患者并未出现任何眼外症状。眼底荧光血管造影是最重要检查,主要表现为斑驳状高荧光,视盘染色和多湖样视网膜下染料积存。所有患者均采用激素治疗,复发病例部分加用了免疫抑制。经过治疗,有超过3/4的患者视力保持在0.6以上,超过半数的患者可以获得1.0以上的视力。系统治疗的患者复发率较低。白内障和青光眼是本病的主要并发症,发生率为20%和9%。     

Parinaud's Oculoglandular Syndrome Due to Herpes Simplex Virus Type 1

Purpose: To describe the clinical findings in a patient with Parinaud's oculoglandular syndrome as an uncommon manifestation of primary herpes simplex virus type 1 (HSV-1) infection. Methods: The clinical course, the laboratory findings, the therapy, and the outcome regarding a 14-year-old girl are described. Results: The culture and PCR detection of HSV-1 on conjunctiva and skin scrapings, along with seroconversion to HSV, confirmed the etiology. The oral and local acyclovir therapy led to a prompt improvement in the patient's symptoms. Conclusion: The solitary ocular-glandular syndrome due to HSV-1 primary infection has never been reported before. Parinaud's oculoglandular syndrome is found in 5% of patients with cat-scratch disease and only on rare occasion associated with other conditions. Herpetic infection should be considered in the differential diagnosis of young patients with conjunctivitis, periorbital swelling, and painful preauricular and submandibular lymphadenopathy, combined with systemic symptoms of malaise and fever.     

Familial Occurrence of Brown's Syndrome and Duane's Retraction Syndrome

Brown's syndrome and Duane's retraction syndrome are well-recognised patterns of incomitant ocular motility with the usual presentation in childhood. Both syndromes are typically sporadic but occasionally may be hereditary, particularly with Duane's retraction syndrome. This short report details the ocular findings in a single family unit showing autosomal dominant inheritance for Duane's retraction syndrome and reduced penetrance for Brown's syndrome with the unusual combination of both Brown's and Duane's retraction syndromes in two family members.