Blepharophimosis ptosis epicanthus inversus syndrome (BPES) (corrected)

The blepharophimosis ptosis epicanthus inversus syndrome (BPES, also known as Waardenburg syndrome) was probably first reported by Ammon in 1841 and discribed more fully by Vignes in 1889. Its primary effects on the soft tissue of the midface are blepharophimosis, ptosis, epicanthus inversus and telecanthus. It starts with the epicanthic folds at about the age of 3-4 years, followed by the correction of the ptosis about 9-12 months later. Early surgery may be necessary for amblyopia. In 1995 the gene locus was identified as 3Q23. BPES is due to a mutation within a single gene, the FOXL2 gene. In female patients an early childhood ovarian insufficiency must be excluded.     

Unilateral anterior persistent fetal vasculature in a child with blepharophimosis-ptosis-epicanthus inversus syndrome: A surgical challenge

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant genetic disease. It is clinically characterized by four major features; blepharophimosis, ptosis, epicanthus inversus, and telecanthus. We report a case of a 1-year-old female with BPES with unilateral anterior persistent fetal vasculature (PFV). On examination, she was found to have all the clinical features of BPES, along with calcified and partially absorbed cataract with elongated ciliary processes in her left eye. B-scan of left eye showed attached retina with no evidence of posterior PFV. Systemic examination was normal. She underwent cataract surgery with primary posterior capsulotomy with intraocular lens implantation under general anesthesia. Literature search did not reveal any previous reports of unilateral anterior PFV and BPES. The clinical features, other associations, and the difficulties in the surgical management of this condition are discussed.     

A novel mutation in the FOXL2 gene in a patient with blepharophimosis syndrome: differential role of the polyalanine tract in the development of the ovary and the eyelid

Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) is an autosomal dominant disorder characterized by abnormalities of the eyelids. We herein report a 12-year-old girl with BPES who had bilateral blepharophimosis, ptosis, hypertelorism, and downslanting palpebral fissures. Mutation analysis revealed the insertion of a cytosine (dup 1036C) within a wild-type run of six cytosines. A comparison of the phenotypic outcomes of the previously described mutations and the dup 1036C mutation reported herein suggest that the outcome is largely dependent on the involvement of the polyalanine tract (residues 221 to 231). We suggest that the polyalanine tract may have a differential role in eyelid and ovarian development and function. Further work is required to clarify whether ovarian function can be predicted on the basis of genotype.     

Double Jeopardy: Blepharophimosis Syndrome with Congenital Nasolacrimal Duct Obstruction in Twins

ABSTRACT

Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant disorder characterized by bilateral ptosis with poor levator function, epicanthus inversus and shortened horizontal palpebral fissures. Method: Eighteen -month -old twin sisters presented with history of watering from their left eyes since birth. Examination revealed features of BPES with left congenital nasolacrimal duct obstruction in both. Result: the twins underwent therapeutic probing, which was successful in one and failed in the other. the second child was subsequently managed by external dacryocystorhinostomy. Conclusion: To our knowledge, this is the first report of Blepharophimosis syndrome with congenital nasolacrimal duct obstruction occurring in twin sisters.     

Wakayama Symposium: Notch-FoxL2-α-SMA Axis in Eyelid Levator Muscle Development and Congenital Blepharophimosis

This review summarizes our recent findings regarding the Notch signaling pathway in regulating normal eyelid morphogenesis and its role in the pathogenesis of human congenital blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). We used genetic and molecular biological approaches to investigate the mechanism by which Notch1 activation controls expression of FoxL2, which in turn activates smooth muscle actin gene expression in periocular mesenchyma to control eyelid levator smooth muscle formation.     

先天性睑裂狭小综合征与FOXL2基因突变研究进展

先天性睑裂狭小综合征(blepharophimosis-ptosis-epicanthus inversus syndrome,BPES)是一种罕见的常染色显性遗传病。BPES分为两型,研究表明FOXL2基因是BPES的致病基因,在BPESⅠ型和Ⅱ型患者中均存在FOXL2基因突变。中外许多研究者对BPES家系或者散发病例的FOXL2基因突变进行了研究。对于近5a关于BPES及FOXL2基因突变的研究情况在此作一综述。     

The incidence of strabismus and refractive error in patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES)

A retrospective review was carried out of 204 patients with blepharophimosis, (blepharo) ptosis and epicanthus inversus syndrome (BPES). Of these, 94 (46%) had an autosomal dominant family history of BPES. Forty (20%) had manifest strabismus. Of these, 28 (70%) had esotropia, 10 (25%) had exotropia and 2 (5%) had hypertropia. Twelve (6%) patients had nystagmus. Seventy (34%) patients had a significant refractive error requiring spectacles. Twenty-one (30%) of these patients had anisometropic hypermetropia and 24 (34%) had anisometropic myopia. Forty-three patients had bilateral amblyopia and 40 had unilateral amblyopia, with 26 (65%) of these undergoing occlusion treatment. Of these, 14 had strabismus and refractive error, 7 refractive error only, 2 strabismus only and 3 neither refractive error nor strabismus. We conclude that there is a higher incidence of strabismus and refractive error in patients with BPES than in the normal population.     

The incidence of strabismus and refractive error in patients with blepharophimosis,ptosis and epicanthus inversus syndrome (BPES)

A retrospective review was carried out of 204 patients with blepharophimosis, (blepharo)ptosis and epicanthus inversus syndrome (BPES). Of these, 94 (46%) had an autosomal dominant family history of BPES. Forty (20%) had manifest strabismus. Of these, 28 (70%) had esotropia, 10 (25%) had exotropia and 2 (5%) had hypertropia. Twelve (6%) patients had nystagmus. Seventy (34%) patients had a significant refractive error requiring spectacles. Twenty-one (30%) of these patients had anisometropic hypermetropia and 24 (34%) had anisometropic myopia. Forty-three patients had bilateral amblyopia and 40 had unilateral amblyopia, with 26 (65%) of these undergoing occlusion treatment. Of these, 14 had strabismus and refractive error, 7 refractive error only, 2 strabismus only and 3 neither refractive error nor strabismus. We conclude that there is a higher incidence of strabismus and refractive error in patients with BPES than in the normal population.     

A Modified One-Stage Early Correction of Blepharophimosis Syndrome Using Tutopatch Slings

Purpose: To investigate the efficacy of a one-stage early correction of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), using bovine pericardium derived membrane (TUTOPATCH®) for the frontalis suspension.

Methods: We prospectively studied 12 eyes from 6 patients (median age 14 months) affected by BPES with severe ptosis. All patients were submitted to a one-stage early correction of ptosis (frontalis suspension with TUTOPACH®) and telecanthus and epicanthus inversus. Upper margin reflex distance (MRD), nasal inner intercanthal distance (IICD), horizontal fissure length (HFL), and IICD/HFL ratio were evaluated using photographs.

Results: The Wilcoxon signed-rank test showed a statistically significant difference between pre- and post-operative MRD, IICD, HFL, and the IICD/HFL ratio.

Conclusion: An early TUTOPATCH-assisted frontalis suspension, together with the correction of telecanthus and epicanthus inversus, is an effective procedure for BPES cases with severe ptosis.     

Blepharophimosis-ptosis-epicanthus inversus syndrome in a girl with chromosome translocation t(2;3)(q33;q23)

We report on a young female patient with the clinical features of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES, OMIM 110100) and a balanced chromosome translocation 46, XX, t(2;3)(q33;q23)dn.BPES is a rare autosomal dominant congenital disorder characterized by the eponymous oculo-facial features that are, in female patients, associated either with (type 1 BPES) or without (type 2 BPES) premature ovarian failure. Both types of BPES are caused by heterozygous mutations in the FOXL2 gene, which is located in chromosome band 3q23. Chromosome aberrations such as balanced rearrangements have only rarely been observed in BPES patients but can provide valuable information about regulatory regions of FOXL2. The translocation in this patient broadens our knowledge of pathogenic mechanisms in BPES and highlights the importance of conventional cytogenetic investigations in patients with negative results of FOXL2 mutation screening as a prerequisite for optimal management and genetic counseling.     

A family with blepharophimosis, ptosis, epicanthus inversus and telecanthus. Occurrence of the hereditary marker in five generations]

The condition with blepharophimosis, ptosis, epicanthus inversus and telecanthus is reported in one family over five generations. The syndrome is transmitted as an autosomal-dominant characteristic with a very high penetrance and expressivity, preferentially affecting and being transmitted by males. Affected females were infertile. There were no other accompanying systemic disorders. A three-year-old boy, who develops deprivation amblyopia, was first treated by levator attachment according to Friedenwald's method. Medical canthal surgery followed two years later to correct the epicanthus and telecanthus. A good clinical result was achieved by performing Mustardè's Z-plasty and shortening of the medial canthal ligament. Alternative techniques are reviewed briefly.     

Single stage surgery for Blepharophimosis syndrome

Purpose:

The purpose of this study was to report the functional and cosmetic outcome of single stage surgical procedure for correction of the classic components of Blepharophimosis syndrome.

Materials and Methods:

We report a retrospective case file review of 11 patients with Blepharophimosis syndrome operated between July 2004 and April 2008. Each patient had undergone the correction of epicanthus inversus, telecanthus, palpebral phimosis, and bilateral ptosis as a single-stage surgical procedure. Patients were examined and photographed before and after surgery. The mean follow-up was 3 years (range 2-6 years).

Results:

A total of 11 patients (8 males, 3 females) with a mean age of 9 years (range 6--22 years) were reviewed. The surgical outcome was assessed both functionally and cosmetically. The mean preoperative visual acuity was 0.729 ± 0.316 SD and the mean postoperative visual acuity was 0.856 ± 0.277 SD (P <0.0428). There was a statistically significant decrease of astigmatism following ptosis correction (P<0.05), improvement of telecanthus (P<0.0001) in terms of IICD (inner intercanthal distance), and HPFL (horizontal palpebral fissure length) (P=0.019) along with improvement of the superior visual field. The mean preoperative and postoperative IICD was 3±0.33 SD and 2.418 ± 0.189 SD, respectively. There was also a significant postoperative improvement of ptosis (P< 0.01), as measured by IPFH (vertical interpalpebral fissure height). All the patients had a stable functional and cosmetic result after a mean follow-up period of 3 years.

Conclusion:

Single-stage surgical correction of the classic anomalies of Blepharophimosis syndrome provides stable and successful long-term results.     

Cutaneous peculiarities in blepharophimosis-ptosis-epicanthus inversus syndrome: report of a case.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare inherited disorder with characteristic oculofacial affection of the eyelid region. Recent results of genetic analysis of the causative gene, as well as a hitherto unknown association with hormone-dependent endometrial carcinoma, motivated us to review this syndrome.     

Blepharophimosis-ptosis-epicanthus inversus syndrome: objective analysis of surgical outcome in patients from a single unit

BACKGROUND: The aim was to objectively assess surgical outcome in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). METHOD: Retrospective review of 14 consecutive patients with BPES. Mustardé double z plasty (at about age 4) and autogenous fascia lata Crawford brow suspension (9-12 months later) were used in all. One consultant performed all operations. Patient photographs were scanned and magnified for analysis. Preoperative and postoperative intercanthal distance, vertical palpebral aperture and cosmetic outcome were measured. Values were converted into ratios. RESULTS: Bilateral (mildly asymmetrical) ptosis and symmetrical epicanthic folds were found in all preoperatively. Seventy-one per cent had severe folds. Preoperative intercanthal distance ratio range was 1.26-1.60 (non-BPES=1.0). Median reduction post surgery was 26% (P=0.001, Wilcoxon's signed ranks test). Patients with largest preoperative ratio displayed greatest correction (P=0.029). Mustardé technique completely abolished all epicanthic folds and unmasked prominent caruncles in all. Fifty per cent had mild scarring postoperatively in the medial canthal region. Median change in marginal reflex distance ratio (right)=22.2% (P=0.012), left=18.2% (P=0.008), Wilcoxon's signed ranks tests. Postoperatively all had formed eyelid creases with improved upper lid position symmetry. CONCLUSIONS: This is the first known study objectively assessing surgical outcome in BPES. Mustardé double z plasty and Crawford autogenous fascia lata brow suspension are an effective surgical combination in the treatment of this syndrome, with overall cosmetic benefit.     

Surgical treatment of congenital eyelid malpositions in children

Congenital eyelid malpositions can be isolated or associated with other structures such as the eyeball, ocular muscles, and lacrimal pathways. It is important to separate eyelid malpositions, which are topographical disorders, from eyelid malformations, which are constitutional morphological disorders. Only eyelid malpositions will be described in this paper, with a distinction made between static and dynamic disorders. Static disorders include epiblepharon, congenital ectropion and entropion, epicanthus, telecanthus, and centurion syndrome. Dynamic disorders group ptosis and congenital eyelid retractions. Epiblepharon is characterized by the absence of adhesion between the lower eyelid retractors and the orbicularis-skin layer, which allows the anterior lamella to roll over. Congenital entropion and ectropion are very rare. They most often require surgical treatment. Epicanthus involves a semi-lunar fold of skin extending from the upper eyelid across the medial canthal area to the margin of the lower eyelid. Four types (supra-ciliaris, palpebralis, tarsalis and inversus) of epicanthus are described. Treatment requires surgery. Telecanthus is defined as an increased distance between canthi. Primary telecanthus results from attenuation of the medial canthal tendons and is usually associated with other soft tIssue abnormalities such as epicanthus or blepharophimosis, or is seen after trauma. Secondary telecanthus is caused by underlying bony malpositions with an abnormal separation between the orbits because of an increased thickness of the interorbital bones such as that seen in hypertelorism or in other complex craniofacial syndromes. Euryblepharon is distinguished by an enlargement of the horizontal palpebral fissure associated with enlarged eyelids. The etiology is unknown and patients may benefit from surgery. Congenital ptosis is characterized by a deficiency of the levator muscle. They are most often unilateral and isolated. When associated with other abnormalities such as squint, synkinesis, blepharophimosis, or craniofacial syndromes, surgical treatment may require several-stage procedures. On the other hand, isolated congenital ptosis is usually treated in childhood (3-6 years) in a single stage. Congenital eyelid retractions may affect either the lower or the upper eyelid. They make up a rare condition and most cases are associated with craniofacial syndromes such as Crouzon or Apert syndromes. Upper eyelid retractions may spontaneously improve in some cases, but lower eyelid retractions do not. Treatment requires surgery, depending on the corneal consequences.     

先天性小睑裂综合征FOXL2基因缺失和突变分析

目的 对5例先天性小睑裂综合征(BPES)患者行遗传学分析,探讨基因型与表型的关系.方法 综合应用核型分析、荧光原位杂交(FISH)、单核苷酸多态性微阵列(SNP array)、聚合酶链反应及DNA测序技术对1例BPES伴智力障碍和4例单纯BPES患者行FOXL2基因缺失和突变分析.结果 BPES伴智力障碍患者染色体3q22.1-q23存在包含FOXL2基因在内约9.4 Mb的杂合性缺失;例2和例3患者FOXL2基因存在c.704delG杂合突变,已报道该突变病例的临床表型为Ⅰ型BPES,但例3临床表现为Ⅱ型BPES;例4和例5未检测到突变.结论 染色体3q22.1-q23可能存在导致智力障碍的相关基因;FOXL2基因c.704delG杂合突变(表达截短蛋白)可导致Ⅰ和Ⅱ型BPES.     

Eye manifestations of fetal alcohol syndrome]

Alcohol is the most frequent and most important teratogenic agent causing mental and physical retardation in childhood. The alcohol fetal syndrome is characterized by pre- and postnatal growth retardation, hypotonia, hyperactivity, microcephalus, mental retardation and typical craniofacial malformations. The latter includes short palpebral fissures, a poorly developed philtrum, thin upper lip vermillion, short mandibles, a flattened midface structure and dysplastic ears. Ophthalmological signs occur in 90% and include epicanthus, ptosis, myopia, optic nerve hypoplasia and tortuous retinal vessels. Microphthalmus, coloboma and Peters' anomaly have also been described. Five children with alcohol embryopathy are presented. The histopathological findings of the enucleated eye of a 6th child with alcohol embryopathy which was sent to us for examination and which revealed an anterior staphyloma with Peters' anomaly is also described. Ophthalmologists should be aware of alcohol in pregnancy as a preventable cause of eye malformation.     

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.