Popliteal pterygium syndrome is a rare congenital disorder that consists of popliteal webs and craniofacial, genitourinary and extremity anomalies. Only moderate successful surgical excision of the fibrotic band within the popliteal web has been reported because the nerves and vessels in the affected site are short and displaced into the web and they are attached to adjacent tissues. We performed hamstring tenotomy on the ischial tuberosity, tenotomy of the flexor hallucis longus and Z-lengthening of the Achilles tendon on the ankle in our patient, and this was followed by gradual correction using an Ilizarov external fixator. Full extension of the knee joint was achieved at the ninth postoperative week. However, some recurrence of flexion contracture was noted at two years follow-up. Gradual soft tissue lengthening with an Ilizarov external fixator can be one of the optimal procedures when excision of a fibrous band and Z-plasty are not possible due to severe adhesion of the nerves and vessels into a fibrotic band. However, a cautious approach is recommended when considering the high risk of recurrence.
Popliteal pterygium syndrome; External fixator; Ilizarov
Popliteal pterygium syndrome (PPS) is a rare autosomal dominant disorder, thought to occur with an incidence of approximately 1 in 300 000 live births. The main clinical manifestations are popliteal webbing, cleft lip, cleft palate, lower lip pits, syndactyly, and genital and nail anomalies. This report describes the clinical features in two families with PPS and one isolated case, showing the range of anomalies found both within and between the families. PPS has some features in common with Van der Woude syndrome (VWS), also inherited as an autosomal dominant condition, with cleft lip/palate and, more distinctively, lower lip pits. Although the gene for VWS has not yet been identified, it has been localised to within 1.6 cM in the region 1q32-41. To determine whether PPS and VWS represent allelic forms of the same gene, three families were genotyped for markers flanking and within the critical region. A multipoint lod score of 2.7 was obtained, with no evidence of recombination, supporting the hypothesis that these two disorders are allelic.
Keywords: pterygium; van der Woude syndrome; cleft lip; cleft palate
Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix–turn–helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-α and -β after viral infection1, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32–q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits4, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies5. Phenotypic overlap6 and linkage data7 suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.
Escobar syndrome or multiple pterygium syndrome is characterized by a web across every flexion crease in the extremities, most notably the popliteal space. In addition, this syndrome is associated with two other structural anomalies: a vertical talus and congenital lordoscoliosis. We present a case report of a patient with Escobar syndrome who was initially managed conservatively and subsequently had severe and debilitating progression and respiratory decompensation ultimately requiring surgical intervention.
After preoperative evaluation by a pediatrician, pulmonologist, and otolaryngologist, the patient underwent one-stage anterior and posterior spinal fusion with instrumentation as well as multiple osteotomies, rib resections, and vertebrectomies.
The patient’s postoperative course was complicated by wound necrosis requiring irrigation and debridement, a urinary tract infection, and a tracheostomy for persistent atelectasis. The patient eventually recovered from all complications. There were never any focal neurologic deficits. The patient had a 3-year follow-up with radiographically confirmed maintenance of correction. Fusion was obtained in the anterior and posterior segments. Clinically, the patient is able to stand upright, can participate in functional activities, and has not required any pain medication. The patient’s functional vital capacity improved from 23% predicted preoperatively to 60% predicted postoperatively.
Patients with severe spinal deformity secondary to Escobar syndrome can be successfully treated surgically. We propose early surgical intervention in this group to prevent curve progression, restrictive lung disease, and the need for complex salvage procedures.
Escobar syndrome; spinal deformity; restrictive lung disease; multiple pterygium syndrome; lordoscoliosis
Cleft lip and cleft palate (CLP) are common disorders that occur either as part of a syndrome, where structures other than the lip and palate are affected, or in the absence of other anomalies. Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant disorders characterized by combinations of cleft lip, CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6). IRF6 belongs to a family of transcription factors that share a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain. To date, mutation analyses have suggested a broad genotype–phenotype correlation in which missense and nonsense mutations occurring throughout IRF6 may cause VWS; in contrast, PPS-causing mutations are highly associated with the DNA-binding domain, and appear to preferentially affect residues that are predicted to interact directly with the DNA. Nevertheless, this genotype–phenotype correlation is based on the analysis of structural models rather than on the investigation of the DNA-binding properties of IRF6. Moreover, the effects of mutations in the protein interaction domain have not been analysed. In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6. In addition, we have demonstrated that IRF6 functions as a co-operative transcriptional activator and that mutations in the protein interaction domain of IRF6 disrupt this activity.
The multiple pterygium syndrome is a rare autosomal recessive condition characterised by arthrogryposis multiplex congenita, pterygia of the neck, fingers, and antecubital, popliteal, and intercrural areas, growth retardation, and facial, vertebral, and genital anomalies. We present two unrelated patients of 17 and 6 years of age, respectively, affected with this condition. We describe the natural history of their disorder since birth and review the spectrum of phenotypic variation of the multiple pterygium syndrome in 25 published cases.
Lethal multiple pterygium (LMP) is a series of disorders of fetal formation with a heterogeneous range of manifestations that generally include cystic hygroma, pulmonary hypoplasia, cleft palate, cryptorchidism, joint contractures, fetal akinesia, heart defects, growth restriction, and intestinal malrotation. The prenatal diagnosis of this syndrome is suspected when two-dimensional ultrasound (2DUS) scan shows several malformations.. The three-dimensional ultrasound (3DUS) in rendering mode permits the spatial visualization of these malformations, allowing better understanding of this anomaly by parents. We report a case of a fetus in the second trimester with multiple abnormalities suggestive of LMP that were identified using 2DUS, and emphasize the importance of 3DUS in counseling the parents.
Lethal multiple pterygium; prenatal diagnosis; three-dimensional ultrasound; two-dimensional ultrasound
IRF6 is a transcription factor that, when mutated, causes allelic autosomal dominant clefting syndromes, Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS). We compared the distribution of IRF6 coding and splice site mutations from 549 VWS or PPS families to that of variants from the 1000 Genomes and NHLBI Exome Sequencing Projects.
We compiled all published pathogenic IRF6 mutations and performed direct sequencing of IRF6 in VWS/PPS families.
While mutations causing VWS/PPS were non-randomly distributed with significantly increased frequencies in the DNA-binding domain (p=0.0001), variants found in controls were rare and evenly distributed in IRF6. Out of 194 different missense or nonsense variants described as potentially pathogenic, we identified only two in over 6000 controls. 5.9% of missense mutations in patients were reported by PolyPhen and SIFT as benign; suggesting that use of current in silico prediction models to determine function can have significant false negatives.
Mutation of IRF6 occurs infrequently in controls, suggesting that for IRF6 there is a high probability that disruption of the coding sequence, particularly the DNA-binding domain, will result in syndromic features. Prior associations of coding sequence variants in IRF6 with clefting syndromes have had few false positives.
Van der Woude; exome; cleft; popliteal pterygium; mutation
Two additional families with popliteal pterygium syndrome are presented. Using previously published pedigrees, as well as the ones reported here, evidence is presented that supports an autosomal dominant mode of inheritance for this syndrome. Analysis of previous familial cases showed a large degree of between and within-family variation. The segregation analysis supports the dominant hypothesis (P=0.5).
The pterygium syndrome consists of the neck, the antecubital fossae and the popliteal regions together with flexion deformities of the limb joints and anomalies of the vertebrae. A family, three offspring of which appear to be affected with the same disorder, is presented. All three are female; there is also a normal female child of the same union.
Three sibs and their mother with features of a multiple pterygium syndrome are reported. Inheritance in this family is consistent with autosomal dominant inheritance with great variation in severity between affected subjects. The importance of examining other family members closely in cases of multiple pterygium is emphasised.
Interferon Regulatory Factor 6 (IRF6) encodes a member of the IRF family of transcription factors. Mutations in IRF6 cause Van der Woude (VWS) and popliteal pterygium syndromes (PPS), two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic mutations in IRF6 between two large geographically distinct collections of families with VWS and between one collection of families with PPS.
We performed direct sequence analysis of IRF6 exons on samples from three collections, two with VWS and one with PPS.
We identified mutations in IRF6 exons in 68% of families in both VWS collections and in 97% of families with PPS. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the IRF6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the VWS collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the PPS collection were missense. Further, the missense mutations associated with PPS were localized significantly to exon 4, at residues that are predicted to bind directly to DNA.
The non-random distribution of mutations in the IRF6 exons suggests a two-tier approach for efficient mutation screens for IRF6. The type and distribution of mutations are consistent with the hypothesis that VWS is caused by haploinsufficiency of IRF6. On the other hand, the distribution of PPS-associated mutations suggests a different, though not mutually exclusive, effect on IRF6 function.
Cleft lip and palate; mutation; haploinsufficiency; dominant negative; cryptic splice site; CpG
A pterygium, a wing-like thickening, of the bulbar conjunctiva is of environmental interest because it can occur on prolonged exposure to wind and weather. We describe a family with pterygium in two generations without a history of unusual exposure to the elements. There were six females and five males (including a set of male twins) with seven bilateral and four unilateral pterygia. The onset was unique in being in early adulthood, from the late teens through the twenties. This new genetic form can be distinguished by the age of onset from congenital and mid-adult pterygia, which are inherited as autosomal dominant traits. Irrespective of age, the treatment of conjunctival pterygium is surgical excision.
The clinical features of the multiple pterygium syndrome are multiple congenital joint contractures, multiple skin webs, camptodactyly, vertebral anomalies, short stature, ptosis, and antimongoloid eye slant. We present 11 new cases to show the evolution of the full phenotype from birth and to confirm autosomal recessive inheritance. We emphasise morbidity secondary to respiratory impairment and that conductive deafness may be part of the syndrome.
The purpose of this study was to report outcomes of infectious scleritis after pterygium surgery, managed with antibiotic therapies and early scleral debridement.
Retrospective chart review of 13 consecutive cases of infectious scleritis after pterygium excision between 1999 and 2009 was conducted. Collected data included prior medical and surgical history, latency period between pterygium surgery and presentation of infectious scleritis, culture and histopathologic findings, antibiotic regimen, length of hospital stay, visual acuity before and after treatment, and complications.
Median follow-up was at 14 months. Twelve patients underwent prompt surgical debridement after infectious scleritis diagnosis (median, 2.5 days). Debridement was delayed in one patient. Median hospital stay was 3 days. Best-corrected visual acuity improved in ten patients, remained stable in one patient, and decreased in two patients following treatment. Complications included scleral thinning requiring scleral patch graft (1/13), glaucoma (3/13), and progression to phthisis bulbi (1/13). No patients required enucleation.
In contrast to the generally poor outcomes in the literature, early surgical debridement of pterygium-associated infectious scleritis appears to offer improved prognosis.
Infectious scleritis; Pterygium excision; Surgical debridement; Biofilm; Medicine & Public Health; Ophthalmology
To report the efficacy, safety, and reliability of autologous cryoprecipitate in pterygium excision surgery and to compare it with the traditional method of using absorbable sutures, in regard to surgical time and the patient comfort.
Materials and Methods:
A prospective interventional clinical study was carried out in a specialized eye clinic. A total of 54 patients (90 eyes) underwent surgical excision of the nasal pterygium (whether primary or recurrent) with conjunctival autograft obtained from the same eye. Patients were divided into two groups. Autologous cryoprecipitate was used in 47 eyes (glue group), and absorbable sutures (8/0 vicryl) were used in 43 eyes (suture group) to attach the free conjunctival graft. There were 42 primary and 48 recurrent nasal pterygia that were included in the study. The surgical time was noted, and post-operative pain was graded. Follow-up period ranged from 6 months to 18 months (mean 12 months). P < 0.05 was statistically significant.
The medians of the visual analogue scale values were significantly lower in the glue group (P < 0.05). The median surgical time was statistically significantly lower at 11 min (range 9 min to 15 min) in the glue group, compared to 21 min (range 12 min to 28 min) for the suture group (P < 0.05). No significant intraoperative or post-operative complications were noted. Recurrence rate was 12%, and all recurrence cases occurred in the sutures group.
Application of autologous cryoprecipitate glue instead of sutures for attaching the free conjunctival graft in pterygium surgery resulted in less post-operative pain and shorter surgical time. Additionally, there were no cases of recurrence during the follow-up in patients who received autologous cryoprecipitate glue during pterygium surgery.
Autologous Cryoprecipitate; Conjunctival Autografts; Pterygium Excision
Primary pterygium in children is uncommon but is associated with severe visual problems. Astigmatism is the main visual problem caused by pterygium. Significant amounts of astigmatism occur long before a pterygium encroaches the visual axis. Early surgical intervention is safe and effective. It is associated with significant visual improvement in outcome. This is a case report on seven-year-old Malay boy who presented with a growth over nasal aspect of the right eye of 1 year duration. His right eye visual acuity is affected up to 6/12. The dilemma pased to early surgical interview is the high rate of recurrancean the young age group. This problem is highlighted in this case report.
AIM—To report cases of scleral necrosis after simple pterygium excision in which adjunctive treatment was not used.
METHODS—We reviewed four patients who presented with scleral melt after pterygium excision without the use of adjunctive treatment in the form of β irradiation, mitomycin C, or thiotepa. Each patient was thoroughly investigated to exclude underlying disease.
RESULTS—Certain similarities were found between our patients with pterygium melt and cases of surgically induced necrotising scleritis including the location of melt, associated inflammation, and its response to steroid treatment in the latent period before they presented.
CONCLUSION—Bare sclera pterygium excision can cause surgically induced necrotising scleritis years after the surgery.
AIM—To describe the prevalence of and risk factors for pterygium in a population based sample of residents of the Australian state of Victoria who were aged 40 years and older.
METHODS—The strata comprised nine randomly selected clusters from the Melbourne statistical division, 14 nursing homes randomly selected from the nursing homes within a 5 kilometre radius of the nine Melbourne clusters, and four randomly selected clusters from rural Victoria. Pterygium was measured in millimetres from the tip to the middle of the base. During an interview, people were queried about previous ocular surgery, including surgical removal of pterygium, and their lifetime exposure to sunlight.
RESULTS—5147 people participated. They ranged in age from 40 to 101 years and 2850 (55.4%) were female. Only one person in the Melbourne cohort reported previous pterygium surgery, and seven rural residents reported previous surgery; this information was unavailable for the nursing home residents. Pterygium was present upon clinical examination in 39 (1.2%) of the 3229 Melbourne residents who had the clinical examination, six (1.7%) of the nursing home residents, and 96 (6.7%) of the rural residents. The overall weighted population rate in the population was 2.83% (95% CL 2.35, 3.31). The independent risk factors for pterygium were found to be age (OR=1.23, 95% CL=1.06, 1.44), male sex (OR=2.02, 95% CL=1.35, 3.03), rural residence (OR=5.28, 95% CL=3.56, 7.84), and lifetime ocular sun exposure (OR=1.63, 95% CL=1.18, 2.25). The attributable risk of sunlight and pterygium was 43.6% (95% CL=42.7, 44.6). The result was the same when ocular UV-B exposure was substituted in the model for broad band sun exposure.
CONCLUSION—Pterygium is a significant public health problem in rural areas, primarily as a result of ocular sun exposure.
Although pterygium excision with conjunctival autograft is a widely performed surgical procedure, surgically induced necrotizing scleritis (SINS) following such surgery is extremely rare.
A 68-year-old man underwent nasal pterygium excision with conjunctival autograft uneventfully. On postoperative day 17, the conjunctival graft was avascular, with epithelial defect. Although topical steroid and antibacterial treatments were continued, the graft and sclera melted, with the ischemic sclera showing gradual thinning. The thinning area spread to the adjoining cornea, and active inflammation with epithelial defect was observed adjacent to the site of thinning.
Systemic and microbiological examination was noncontributory. The patient was suspected of having SINS, and administration of oral prednisolone was started. Although the necrotic area was reduced temporarily, medication was discontinued due to nausea, and the area of thinning increased. Conjunctival flap surgery was later performed, and the graft was well accepted.
SINS must be considered in the differential diagnosis of patients with scleritis following pterygium surgery, especially if radiation or mitomycin C has not been used.
scleritis; pterygium; pterygium surgery; conjunctival autograft; SINS
AIM: The study was designed to evaluate the long term results of intraoperative mitomycin C in patients with one recurrence of pterygium. METHODS: In 45 white patients with one recurrence of pterygium the 'bare sclera technique' was performed and a sterile sponge soaked in a 0.2 mg/ml (0.02%) mitomycin C solution was placed intraoperatively on the sclera for 3 minutes. The control group underwent surgical excision only. Recurrences were analysed by the chi 2 test and the method of Kaplan-Meier (life table analysis); the difference between survival curves was tested by the log rank test. The chi 2 test with Yates's correction or Fisher's exact test were used to analyse the difference in complications and side effects between the two groups. RESULTS: After a mean postoperative follow up of 34.55 (SD 13.70) months, 6 recurrences (12.5%) were observed in the mitomycin C treated patients and 16 (35.6%) in the control patients (p = 0.027). The 24 and 48 month life table success rates were 89% and 83% in the mitomycin C treated group and 66% and 63% in the control group, respectively (p = 0.022). No severe side effects appeared during follow up. Superficial punctate keratitis appeared in the early postoperative period in only seven mitomycin C treated eyes (15.5%) (p = 0.018). CONCLUSION: This study confirms the efficacy of intraoperative mitomycin C in improving the success rate after recurrent pterygium surgical excision.
Pterygium is a proliferative disease with hyperplastic growth of corneoconjunctival fibro vascular tissue onto the cornea. Surgical therapy can be used to successfully manage pterygia; however, recurrence remains a problem. To reduce recurrence, surgical management may include autoconjunctival grafting, lamellar keratoplasty, amniotic membrane transplantation, and intraoperative antimetabolites application.
To assess the safety and the efficacy of intraoperative mitomycin C (MMC) and 5-fluorouracil (5-FU) application in preventing recurrence of pterygium after excision.
Patients and methods
The study design is a prospective, randomized clinical trial. A total of 50 patients with bilateral pterygium were recruited for the study. The first group of patients (25) underwent surgical excision of the pterygium with bare sclera in one eye and MMC was applied as adjunctive therapy for the other eye. In the second group 5-FU was used instead of MMC. Recurrences and postoperative complications were measured in the two groups. The mean follow up period of the patients was 18.8 months. Chi square test, odds ratio, and frequency distribution were used to determine significance levels; P-values <0.05 were considered statistically significant.
In group 1 the recurrence rate was 8% for the MMC treated eyes and 32% for their fellow eyes (P = 0.03). In group 2 the rate was 18% for the 5-FU treated eyes and 34% for their fellow eyes (P = 0.07). No serious complications were recorded in either group.
Both MMC and 5-FU reduce the recurrence rate of pterygium after simple surgical excision; statistically, the effect of the former was significant, but insignificant for the latter. Both antimetabolites were safe during the whole study period, but 5-FU recurrent cases showed cosmetically unacceptable appearances with excessive vascularization. MMC, but not 5-FU, is recommended as an adjunctive therapy to prevent recurrence of pterygium after surgical excision.
recurrent pterygium; mitomycin C; 5-fluorouracil; adjunctive therapy
Surgeon‐dependent variables influencing pterygium surgical outcome using the conjunctival autograft technique include conjunctival retraction as a consequence of subepithelial contracting fibrous tissue, and autograft inversion causing necrosis and sloughing of the graft.
A simple and useful technique of pterygium excision is described, which helps to ensure the correct surface and linear orientations of the conjunctival autograft, and also defines the end point of adequate excision of the subepithelial connective tissue.
This simple technique of defining the anterior surface and the centrifugal orientation with the letter “G” marked on the graft prevents reverse orientation of the graft.
Pterygium is a common ocular surface pathology in tropical environments. In the early stages, it may be managed medically with topical anti-inflammatory agents and ocular lubricants. However as the disease progresses, surgical excision becomes necessary and several anaesthetic methods may be used to assist this. We share our experience of a 30-year old woman who underwent uneventful pterygium excision using peribulbar lignocain injection with adrenaline. She developed sudden blindness due to central retinal artery occlusion with macular infarction. While peribulbar anaesthesia is generally safe, a remote risk of retinal vascular accident exists and its routine use should be done with caution. Where possible topical anaesthesia with or without intra-lesional injection be employed.
Central retinal artery occlusion; macular infarction; peribulbar anaesthesia; pterygium; retinal ischemia
To evaluate the outcomes of primary pterygium excision with adjunctive amniotic membrane transplantation.
In an interventional case series, consecutive patients with primary pterygia underwent surgical excision with transplantation of preserved amniotic membrane onto bare sclera. Patients were followed for at least 12 months and the results were evaluated in terms of recurrent pterygium growth and complications.
Fifty eyes of 50 consecutive patients including 27 male and 23 female subjects with mean age of 43.36±10.88 years were operated. The pterygia extended onto the corneas for 4.69±1.2 (range 3 to 7) mm. Only one eye (2%) demonstrated recurrent pterygium growth which responded to subconjunctival mitomycin C injection. Another eye (2%) developed amniotic membrane retraction which eventually required a second transplantation leading to complete resolution.
Primary pterygium excision with amniotic membrane transplantation is a safe and effective surgical technique with low recurrence rate.