Early and frequent development of ocular hypertension in children with nephrotic syndrome

Background

Prednisolone, the first-line treatment for children with nephrotic syndrome, causes severe side effects. One of these side effects is ocular hypertension, which can result in severe and permanent visual disturbance. However, the exact prevalence, severity and timing of development of ocular hypertension have yet to be fully explored in this pediatric patient group.

Methods

In this retrospective cohort study, children with nephrotic syndrome treated with prednisolone for their first episode were analyzed. Intraocular pressure was screened with an iCare® tonometer and confirmed with Goldmann applanation tonometry before the initiation of prednisolone treatment and at 1 and 4 weeks thereafter.

Results

A total of 26 children with nephrotic syndrome were included in this study, of whom eight (30.8 %) required treatment with eye drops for ocular hypertension. The median time interval between the diagnosis of ocular hypertension and start of treatment was 9 (range 5–31) days. At relapse of nephrotic syndrome, all children who had undergone treatment for ocular hypertension in their first episode again required treatment for ocular hypertension.

Conclusions

Routine ophthalmologic examination should be conducted from the early phase after the start of prednisolone treatment. In addition, children with episodes of ocular hypertension may be at greater risk of its reappearance with relapse of the nephrotic syndrome.     

Les syndromes oculomoteurs par hyperactivité neurogène et leur traitement

In this chapter we describe a variety of rare but clinically identifiable ocular motor syndromes, including ocular neuromyotonia, superior oblique myokymia, ocular motor synkinesis, third nerve palsy with cyclic spasms, and paroxysmal manifestations of multiple sclerosis. These syndromes share many characteristics. They result from neurogenic hyperactivity, causing episodic spasms of one or several extraocular muscles. The pathophysiology is not fully understood, but it usually includes both a focal and partial lesion of one of the ocular motor nerves and a central rearrangement of neuronal activity in the ocular motor nuclei. Treatment with membrane-stabilizing agents, such as carbamazepine, is usually effective to reduce the symptoms. The above-mentioned syndromes result from a number of different diseases. A proportion of apparently idiopathic cases may be related to a neurovascular compression syndrome.     

Ganglioneuroma, heterochromia iridis, and Horner's syndrome

A child with mediastinal and supraclavicular ganglioneuroma, heterochromia iridis, and Horner's syndrome is described. The authors postulate that the thoracic neoplasm originated as a congenital neuroblastoma with metastasis to the supraclavicular lymph nodes and subsequent benign transformation, and that the ocular abnormalities resulted from sympathetic ganglion injury by the tumor in infancy. This seems to be the first published report of such ocular abnormalities associated with mediastinal ganglioneuroma.     

Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders

Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval. Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children. A different mutation at this codon (R246W), which is highly conserved through evolution, has recently been reported as causing Pierson syndrome. Subsequent LAMB2 mutational screening in six additional families with congenital nephrotic syndrome revealed compound heterozygosity for two novel missense mutations in one family with additional nonspecific ocular anomalies. These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome. This phenotypic variability likely reflects specific genotypes. We conclude that mutational analysis in LAMB2 should be considered in congenital nephrotic syndrome, if no mutations are found in NPHS1, NPHS2, or WT1.     

The use of ocular abnormalities to diagnose X-linked Alport syndrome in children

The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4-19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The early onset retinopathy was associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys (40%) would have been diagnosed with Alport syndrome on the basis of their own or their mother's ocular examinations. None of the six girls (median age 8 years, range 7-14 years) had ocular abnormalities. Hearing loss is usually highly sensitive for the diagnosis of Alport syndrome, but ocular examination of boys and their mothers at the initial consultation is a non-invasive test that is helpful in up to 40% cases.     

Ruptured thoracoabdominal aortic aneurysm in a renal transplant patient with Alport's syndrome

Alport's syndrome is a rare genetic disorder of type IV basement membrane collagen synthesis that typically presents with nephropathy, deafness, and ocular abnormalities. To the best of our knowledge, this is the first report in the world's literature of ruptured thoracoabdominal aortic aneurysm in a young patient with Alport's syndrome and a renal transplant. Hypotheses on an association between collagen disease in Alport's syndrome and aortic aneurysms are discussed.     

Oculodento-osseous dysplasia: review of anaesthetic problems

Oculodento-osseous dysplasia (ODOD) is a rare congenital condition characterized by ocular, nasal, dental, digital and skeletal stigmata. A dual mode of inheritance has led to two distinct clinical forms of the syndrome. The more severe form is distinguished by neurological involvement. These patients will present for multiple general anaesthetics during childhood. A new case of this syndrome is reported and the anaesthetic management described. The principal anaesthetic implication of ODOD is the possibility of difficult intubation due to the combination of bony, dental and nasal anomalies. The neurological and ocular anomalies are also discussed in relation to anaesthesia.;     

Age-related changes in the normal sagittal relationship between globe and orbit.

PURPOSE: To establish the pattern of change in globe protrusion with advancing age. The findings contribute to our understanding of orbital ageing, and are useful in the longitudinal assessment of patients with orbital disease, craniofacial abnormalities and trauma. METHODS: Ocular protrusion from the lateral orbital rim to the corneal apex was measured in 653 Caucasians aged 21-80 years. Healthy subjects only were included in the study excluding those with ocular or orbital diseases. Measurements were taken using a single instrument and observer. Data were analysed for both sexes and each eye separately. RESULTS: The mean exophthalmometry reading in both sexes (318 female and 335 male) was 19+/-2mm. Ninety-eight percent of readings between the two eyes were within 1mm of each other and no subject had greater than 2mm of asymmetry. In all groups there was a negative linear correlation between ocular protrusion and age. This correlation was found to be highly statistically significant in all groups (r=0.56-0.65, p<0.0001). There was no statistically significant difference between change in ocular protrusion with age between the left and right eye for females or males. This study demonstrates a strong association between ocular protrusion and age in a Caucasian population. This association is an almost linear reduction in ocular protrusion with increasing age between the ages of 31 and 80. Asymmetry in ocular protrusion between the two eyes does not develop with increasing age.     

Bilateral iridocorneal endothelial (ICE) syndrome with microspherophakia

Iridocorneal endothelial syndrome is described to be a rare, usually unilateral ocular condition in young females. There are three known overlapping clinical variants of this condition namely, essential iris atrophy, Cogan-Reese and Chandler syndrome. We report a case of bilateral iridocorneal endothelial (ICE) syndrome with microspherophakia. A 25 years old female presented with microspherophakic lens dislocated into anterior chamber in right eye, and displaced inferiorly in left eye. She was also diagnosed with ICE syndrome and underwent lensectomies in both eyes. This unique combination has never been reported before.     

LAMB2基因新突变所致先天性肾病综合征一例及文献复习

目的通过对1例Pierson综合征的女性患儿临床型和基因型分析并进行相关文献复习,以提高对 Pierson综合征的认识。方法检测先证者各项血生化指标以及详细体格检查;二代测序分析先天性肾病综合征相关的21种基因;用 Sanger 方法验证先证者及其父母外显子突变状态。结果先证者血生化检测显示大量蛋白尿（尿蛋白肌酐比53497.1μg/mg）,尿液检测显示隐血＋＋＋,蛋白＋＋＋,低白蛋白血症（16.1 g/L）;基因分析显示先证者LAMB2基因编码区存在复合杂合突变, Exon9c.1176_1178del TCT导致392位苯丙氨酸缺失,来自先证者母亲;Intron29c.4923＋2T〉G导致剪切突变,来自先证者父亲。先证者给予间断输注白蛋白,维持电解质酸碱平衡治疗,因感染于117日龄死亡。根据以上临床资料,总结复习相关文献。结论该患儿的LAMB2的复合杂合突变是导致Pierson综合征的新突变;Pierson综合征肾外症状表型和肾脏表型并不平衡,肾脏表型可能与基因突变所致蛋白功能缺陷程度相关,同时也受到表观遗传学影响;而眼部表型可能与LAMB2的基因型相关;因此对于婴儿期出现的肾病综合征或肾病范围蛋白尿的患儿,无论是否存在肾外的症状均应进行相关基因分析除外Pierson综合征。随着二代测序在临床的应用,必须仔细分析以确定二代测序所发现的新突变与疾病的关系。     

Morquio's syndrome and its anaesthetic considerations

Morquio's syndrome is an inherited disorder characterized by excessive excretion of keratan sulphate in the urine. The anaesthetic care of these patients should take into consideration respiratory, craniofacial, cardiac, skeletal, ocular and hepatic abnormalities. We report the case of a child with Morquio's syndrome who presented for stabilization of the cervical spine, and discuss the issues relevant to the anaesthesiologist.     

Tarsal polishing and mucous membrane grafting for cicatricial entropion, trichiasis and epidermalization

In a manner similar to dermabrasion, epidermalized tarsal conjunctiva is polished and then the tarsus is grafted with full-thickness buccal mucous membrane. This has been applied with rewarding results in patients afflicted with Stevens-Johnson syndrome, ocular pemphigoid and scarred eyelids with secondary epidermalization.     

Successful mitral valve replacement in a patient with Ehlers-Danlos syndrome type VI

A 40-year-old patient with Ehlers-Danlos syndrome type VI (ocular type) had mitral regurgitation due to mitral valve prolapse. Because the patient's tissue was fragile, we replaced the mitral valve with a reinforced prosthetic valve to prevent paravalvular leakage. The excised mitral leaflet showed significant myxomatous change and decrease in collagen fibers. We believe this is the first report of cardiac surgery in a patient with Ehlers-Danlos syndrome type VI.     

伴食管及胃巨大平滑肌瘤Alport综合征的影像学特征

Alport综合征是遗传性肾小球基底膜疾病,血尿、感音神经性耳聋及进行性肾功能减退是主要临床症状,可伴有眼部异常,此外极少数患者伴有弥漫性平滑肌瘤.Alport综合征伴弥漫性平滑肌瘤发生率低,受累部位常为食管、气管和女性生殖道等,并可出现吞咽困难、餐后呕吐,反复发作性支气管炎等呼吸困难的症状,其中以弥漫性食管平滑肌瘤最常见.同时伴有食管及胃巨大平滑肌瘤的Alport综合征的患者罕见,通过分析临床资料,总结该病的影像学表现,旨在提高对该病的认识及诊断水平.     

Variable phenotype of Pierson syndrome

Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes the laminin β2 chain, and is clinically characterized by congenital nephrotic syndrome (CNS) and bilateral microcoria. Here, we describe two cases of Pierson syndrome involving atypical phenotypes. Patient 1 presented with congenital microcoria and infantile nephrotic syndrome. Despite persistent nephrotic syndrome, her renal function was maintained normally until she was 6 years old. Genetic analysis revealed two frame-shifting deletions (truncating mutations) in the LAMB2 gene. Patient 2 presented with isolated CNS without ocular involvement. Her renal function deteriorated progressively over several months, and retinal detachment in the right eye developed when she was aged 10 months. LAMB2 analysis revealed a missense mutation in one allele and a frame-shifting deletion in the other allele. Electron microscopy of a renal biopsy revealed irregular lamellation of the glomerular basement membrane (GBM) in both patients. The phenotypes of Pierson syndrome vary widely, and the severity of the renal phenotype is not always parallel to that of the ocular phenotype. The phenotypic variability likely reflects genotype–phenotype correlations, but unknown genetic or environmental modifiers may play an additional role. Ultrastructural changes of the GBM are a useful diagnostic indicator.     

Choroidal hemangioma in Sturge Weber syndrome: Case series with confirmed tissue diagnosis

IntroductionSturge-weber syndrome (SWS) is a rare condition that presents with a typical facial port-wine stain, neurological manifestations such as seizures, and ocular involvement by glaucoma and/or choroidal hemangioma. In this series we demonstrate the histopathological details of the primary ocular involvement as well as the late blinding secondary ocular changes.Presentation of casesSeven cases were included with the diagnosis of choroidal hemangioma in association with SWS (6 enucleations and one evisceration). Male to female ratio was 4:3. Age at enucleation/evisceration ranged from 25 to 68 years with a median of 42 years. Five cases had history of glaucoma (71.4%). Diffuse hemangioma was found in all (4 cavernous and 3 mixed cavernous/capillary type). Conjunctival and episcleral hemangiomas were found in 3/7. Iris neovascularization and retinal detachment were confirmed in 5/7 cases each (71%).DiscussionOur demographic and histopathological findings parallel what was previously concluded in the literature about the lack of gender predilection in SWS, and the most common ocular presentations of glaucoma and choroidal hemangioma, which is mostly diffuse in nature. The hemangioma type was found to be mostly cavernous followed by mixed capillary and cavernous. We demonstrated late associated ocular changes such as cataract, iris neovascularization, exudative retinal detachment, retinal pigment epithelium hyperplasia/metaplasia, and optic nerve atrophy, all of which aid in the poor visual outcome in these patients.ConclusionSturge-weber syndrome is a rare but visually disabling disease due to the associated ocular manifestations of glaucoma and choroidal hemangioma. Multidisciplinary approach because of the diverse presentation of this condition by pediatrician, neurologist, and ophthalmologist is essential with an attempt to preserve vision.     

Anesthetic characteristics and airway evaluation of patients with Weill-Marchesani syndrome

Weill-Marchesani syndrome (WMS) is a genetic connective tissue disorder associated with fibrous tissue hyperplasia. Weill-Marchesani syndrome is characterized by short stature, broad head and other facial abnormalities such as hypoplastic maxilla and distinctive ocular abnormalities. Joint stiffness is one of the features of this syndrome. We report 5 cases with classical features of WMS who were subjected to different ophthalmic procedures. To the best of our knowledge, this is the first series on the anesthetic management of this rare syndrome. We observe that patients with WMS can present for cataract, glaucoma as well as retinal surgery. Special consideration should be given to difficult intubation, cardiac abnormalities and patient positioning.     

Familial aortic dissection of non-Marfan syndrome with mutations in the transforming growth factor-beta receptor type 1 genes

Marfan syndrome is an inherited connective tissue disorder with ocular, skeletal and cardiovascular systems and often causes acute aortic dissection. Interestingly, there have been several reports of familial thoracic aortic dissection in patients with autosomal dominant diseases without Marfan syndrome. Variation of the transforming growth factor-beta receptor (TGFBR) gene is reported to be one of the causes. We report a case of a familial aortic dissection not associated with Marfan syndrome, with mutation of TGFBR type 1. Hereditary aortic dissection of the non-Marfan syndrome that does not have clinical manifestations is not uncommon. Thus, the existence of familial aortic aneurysm should be in mind in diagnosis and treatment.     

Concurrent hyphema and orbital apex syndrome following herpes zoster ophthalmicus in a middle aged lady

IntroductionHyphema and orbital apex syndrome occurring concurrently in a patient with herpes zoster ophthalmicus have not been reported previously. We present a case with these unique findings and discuss the pathogenesis of these conditions and their management.Presentation of caseA 59-year-old Malay lady with underlying diabetes mellitus presented with manifestations of zoster ophthalmicus in the left eye. Two weeks later, she developed total hyphema, and complete ophthalmoplegia suggestive of orbital apex syndrome. She was treated with combination of intravenous acyclovir and oral corticosteroids, and regained full recovery of ocular motility. Total hyphema persisted, and she required surgical intervention.DiscussionHyphema is postulated to occur due to an immune vasculitis affecting the iris vessels. Orbital apex syndrome is probably due to an occlusive vasculitis affecting the vasculature of the extraocular muscles and optic nerve, resulting from a direct invasion by varicella zoster virus or infiltration of perivascular inflammatory cells. Magnetic Resonance Imaging of the brain is essential to exclude possibility of local causes at the orbital apex area.ConclusionHerpes zoster ophthalmicus is an uncommon ocular presentation. Managing two concurrent complications; persistent total hyphema and orbital apex syndrome is a challenging clinical situation. Early diagnosis and prompt treatment are essential to prevent potential blinding situation.     

Facial port-wine stains - clinical stratification and risks of neuro-ocular involvement.

BACKGROUND: Port-wine stains are capillary malformations that commonly involve the skin of the head and neck region. They may affect the underlying subcutaneous tissue and bone, and extend on to adjacent mucous membrane and conjunctiva. Ipsilateral leptomeningeal and ocular choroidal involvement occurs in a small number of cases, with variable clinical manifestations. AIM: To analyse a series of consecutive patients with facial port-wine stains referred to our Vascular Anomalies Centre to (1) stratify their clinical manifestations, and (2) identify the risks of neurological and/or ocular involvement according to topographic pattern. METHODS: Consecutive patients with facial port-wine stains were taken from our Vascular Anomalies Database 1996-2006. Port-wine stains were topographically analysed and mapped to the sensory distribution of division(s) of the trigeminal nerve, cervical plexus, and dorsal rami of the spinal nerves. RESULTS: 158 patients were identified. Many of these patients had extension of their facial port-wine stains or additional separate port-wine stains on their scalp, neck, trunk or limbs. Involvement of adjacent mucosa, conjunctiva, underlying soft tissue and bone was common. Fifteen patients had associated neurological and/or ocular complications. All had port-wine stains in V1 distribution. Additional involvement of V2 and/or V3, and bilaterality were common. Seven of the nine patients (78%) with port-wine stains affecting the entire V1 had neurological and/or ocular involvement. The risk of associated neurological and/or ocular disorder in a patient with partial or full V1 involvement was 26%, glaucoma and epilepsy being the most common manifestations. CONCLUSIONS: The clinical stratification of facial port-wine stains provides a guide to patient counselling and therapeutic interventions. Port-wine stains affecting the entire V1 distribution predict strongly for underlying neurological and/or ocular disorders that require on-going ophthalmological surveillance and/or neurological management. Although the classical Sturge-Weber syndrome encompasses a triad of clinical manifestations, incomplete forms are not uncommon. This neuro-oculo-cutaneous syndrome is believed to be a result of vascular malformations of associated structures derived from the neuroectoderm (facial skin, eye, and parieto-occipital region of the brain and leptomeninges) during the first trimester. However, the pathogenesis of port-wine stains and Sturge-Weber syndrome remains unclear.