Biallelic CPAMD8 variants in a patient with ectopia lentis associated with extraocular systemic features reminiscent of Marfan syndrome

Purpose: To report a case presented with unilateral acute angle closure glaucoma secondary to ectopia lentis (EL) as first manifestation of Marfan syndrome(MFS) Material and Methods: case report Results: A 37-year-old man with patent laser peripheral iridotomy(LPI) in both eyes presented with repeated episodes of acute angle closure glaucoma in his right eye. Scheimpflug photography (Pentacam, Oculus demonstrated bilateral and superotemporal EL. Pupillary dilated slit lamp examination confirmed EL later. Bilateral EL was also diagnosed in the patient's elder brother Transthoracic echocardiography demonstrated mitral valve prolapse in this patient and aortic root dilatation in the patient's elder brother. Genetic evaluations revealed fibrillin1 (FBN1) gene mutation in this patient, his son and the patient's elder brother. The patient and his elder brother were finally diagnosed as MFS based on Ghent nosology. Conclusion: EL should be considered when repeated episodes of acute angle closure glaucoma occurred in young patients with patent LPI. Scheimpflug photography is valuable in providing the correlation between EL and iris plane with fixed-dilated pupil. Early diagnosis and appropriate surgical management of EL can preserve vision in patients with MFS.

Background: Marfan syndrome, an inherited disorder, affecting Fibrillin-1 gene, is a multisystem disorder affecting mainly skeletal, cardiovascular and ocular systems along with involvement of ligaments, lungs, skin and brain, aorta. The diagnosis mainly relies on history and examination. Genetics include Fibrilin-1 gene mutation on chromosome 15, these patients have variable expressivity and penetrance, with heterogenous presentations and symptoms. Case presentation: Here we are presenting a case of 22-year young male with Marfan syndrome having positive family history and typical features i-e tall stature, disproportionately long arms and legs, thin, lean with long extremities, high arched palate, arachnodactyly, pectus carinatum, flat foot, hyperflexible joints, positive thumb and wrist sign, mitral regurgitation and mitral valve prolapse presenting with ocular complications, bilateral ectopia lentis (upward deviation of lens with preserved zonular fibers) and rhegmatogeous retinal detachment. The diagnosis of Marfan was made on clinical grounds and Ghent criteria (score of 8), which was further strengthened by ocular and cardiovascular manifestations. Genetic testing was not done in this case. Treatment and outcome: Left eye vitrectomy and aspiration was successfully done. Later after 6 months, on follow up patient developed blurred vision and dark curtain appearing in front of left eye. On ophthalmological review, he had left retinal detachment. He underwent encirclement and pars plana vitrectomy and oil in left eye. Conclusion: Marfan syndrome requires regular monitoring for complications as leaving untreated has adverse outcomes and decreased lifespan. Management requires multidiscilpinary approach, corrective surgeries, medical treatment and regular follow up for screening of complications.

To describe the causes of ectopia lentis (EL) and the outcomes after surgery in a Danish population. The Eye Clinic Rigshospitalet and Kennedy Center in Copenhagen. Retrospective cohort study. Medical records of patients with nontraumatic EL born after 1980 and seen at the Eye Clinic Rigshospitalet and Kennedy Center from 1983 to 2019 were reviewed. Clinical information regarding family history, comorbidities, genetic workup, ophthalmological examinations, and surgical history was retrieved. 72 patients (38 males), of whom 68 had bilateral EL (94.4%) were identified. Marfan syndrome (MFS) was found in 34 (47.2%) and biallelic variants in ADAMTSL4 in 4 (5.6%). Surgery was performed in 38 (52.8%) patients, 66 eyes, with a median age at the time of first eye surgery of 8.4 years (range 0.8 to 39.0 years) and a follow-up of 2.3 years (range 0 to 25.7 years). Intraocular lenses were implanted in 9 (23.7%) (11 eyes). Corrected distance visual acuity improved from 0.7 to 0.2 logMAR (median) in right eyes and from 0.7 to 0.3 logMAR in left eyes postoperatively. 21 patients (56.8%), 42 eyes, did not experience any surgery-related complications. 3 patients (3 eyes) experienced a perioperative tear in the posterior capsule. Temporary postoperative ocular hypertension was reported in 3 patients (7.9%) (3 eyes), and 2 patients (5.4%) (2 eyes) developed persistent ocular hypertension. There were no cases of postoperative retinal detachment. The main reason for EL was MFS. Surgery improved visual acuity, and postoperative ocular hypertension was the most common complication, whereas retinal detachment was not observed.

To evaluate corneal curvature, pachymetry, and endothelial cell density (ECD) in Marfan syndrome (MFS). A case-control study in which K values, pachymetry, and ECD were compared in 39 MFS eyes and 40 control eyes matched for age and refraction was conducted. MFS eyes with lens subluxation also were compared with eyes without subluxation. The mean K(med) value in MFS eyes was lower than in the control eyes, 42.2 ± 1.9 versus 43.4 ± 1.4 dioptres (D), respectively (p = 0.02). Fifteen MFS eyes (38%) and three control eyes (8%) had K(med) values below 41.5 D (p = 0.0012). MFS eyes had generally more corneal astigmatism than control eyes, 1.1 ± 0.9 versus 0.8 ± 0.4 D (p = 0.035), and MFS eyes with lens subluxation had more corneal astigmatism than those without, 1.6 ± 1.1 versus 0.6 ± 0.3 D (p = 0.0002). Nine MFS eyes with corneal astigmatism exceeding 1.5 D also had a subluxated lens. No eyes had keratoconus. The mean pachymetry value was lower in MFS eyes compared to the controls, 485 ± 54.5 versus 514 ± 37.3 μm (p = 0.007); 24 MFS eyes (62%) and 10 control eyes (25%) had measurements below 500 μm (p = 0.01). The mean ECD values were similar in MFS and control eyes, 2815 ± 430 versus 2858 ± 458 cells/mm(2) (p = 0.66). The mean K value, pachymetry, and ECD values did not differ between MFS eyes with and without lens subluxation. Decreased K values and pachymetry could indicate MFS regardless of subluxation. High corneal astigmatism is associated with subluxation in MFS. Subluxation should be identified in MFS eyes with high corneal astigmatism.

Introduction: Marfan syndrome (MFS) is characterized by ectopia lentis (EL) and elongated axial length (AL). The characteristics of AL in young patients with MFS and bilateral EL before the lens surgery are not fully understood. Methods: This study reviewed MFS patients under 20 years old with bilateral EL from January 2015 to October 2020. The Z-scores were introduced in terms of the number of standard deviations from the mean of age-matched normative data. Using Z-scores, the distribution of AL and influence factors were evaluated. The correlations between AL and other biometrics were analyzed. Results: We reviewed 183 patients and enrolled both eyes. The mean age was 8.44 ± 4.69 years. About 36% of the patients were children under 6 years old. The median AL increased from 23.16 mm under 5 years old to 26.20 mm in the 16–20 age group, and when plotted, the trend presented a logarithmic curvature (R² = 0.145, p < 0.001). The median Z-AL score was 1.24. One-third of eyes had Z-score <0. About 20% of the patients had AL difference over 1 mm between the right and left eyes, and the right one had longer Z-AL scores (p = 0.013). The eye complicated with megalocornea (10, 7.04%) had larger Z-AL scores (4.72 ± 3.51 vs. 1.10 ± 2.25, p = 0.002). A positive correlation was found between Z-AL and Z-corneal curvature radius (r = 0.265, p < 0.001). Conclusion: Young patients with bilateral EL but small AL should not be excluded from MFS without systematic examination. The age-adjusted Z-score will facilitate further study of the individual variations in AL across different ages.

Marfan syndrome (MFS) is an autosomal dominant systemic disorder of the connective tissue. Children impacted by the MFS carry the mutation in one of their two alleles of the gene that codes the connective tissue protein fibrillin-1 (FBN-1). MFS influences their effects upon most organs and tissues, in particular the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the reminder of the physique. A case report of MFS with atypical pneumonia has been reported with positive Steinberg sign, thumb sign and wrist sign. Existence of long legs with the positive Walker Murdoch sign. There were no complications such as an aortic aneurysm, ocular lens luxation, or mitral valve prolapse were remarked. Since the patient was lacking such complications based on MFS, he was treated only for atypical pneumonia. Keywords: Marfan Syndrome, Fibrillin-1, Thoracic Aortic Aneurysm or Dissection, Ectopia Lentis

Ectopia lentis is defined as an acquired or hereditary malposition of the crystalline lens due to a zonular deficiency. It can be caused by a trauma or secondary to an underlying systemic disease, such as Marfan syndrome, Weill-Marchesani syndrome and homocystinuria. Marfan Syndrome (MFS) is a disease of the connective tissue mainly affecting the ocular, cardiovascular and skeletal system. Up to 80% of patients with Marfan syndrome develop ectopia lentis, 50% of which occurs before the age of 5. Lens displacement is usually bilateral and symmetrical, and frequently occurs superotemporally. We here report the case of a 17-year-old girl born to consanguineous parents. She presented with behavioral disorders and school problems reported by her parents. On general examination, she was tall for her age and had long, thin fingers. Clinical examination showed visual acuity 2/10 and good pupillary light reflex; the examination of the anterior segment objectified clear cornea, with an increase in anterior chamber depth and bilateral ectopia lentis in the nasal area. Fundus examination was normal. Etiological research didn’t uncover causal effects. The patient underwent phacophagia with implantation of an iris-fixated implant and skin biopsy aimed to confirm the diagnosis of Marfan syndrome.

Summary To report three male Marfan patients from one family, with no skeletal anomalies, but with nasally subluxated lenses in two and bilateral total crystalline lens dislocation into the vitreous cavity in one of them. Ophthalmological, cardiological, orthopaedic evaluation. Although none of the patients had any skeletal abnormalities, all three had ophthalmological involvement. Cardiological examination revealed mitral valve prolapse and aortic root dilatation in all patients. Associated grade 1tricuspid valve insufficiency was present in one patient. Conclusion: Whenever bilateral ectopia lentis is observed, Marfan syndrome should be suspected, and careful systemic evaluation should be carried out in order to avoid overlooking the other systemic life-threatening failures. (TOD Dergisi 2010; 40: 245-7)

Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis, and a distinct "crumpled ear" deformity. While the disorder is similar to Marfan syndrome, it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echocardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.

Marfan syndrome (MFS) is a multisystem connective tissue disorder with primary involvement of the ocular, cardiovascular, and skeletal systems. We report on eight patients, all presenting initially with bilateral ectopia lentis (EL) during early childhood. These individuals did not have systemic manifestations of MFS, and did not fulfill the revised Ghent diagnostic criteria. However, all patients had demonstratable, disease-causing missense mutations in the FBN1 gene. Based on molecular results, cardiovascular imaging was recommended and led to the identification of mild aortic root changes in seven of the eight patients. The remaining patient had mitral valve prolapse with a normal appearing thoracic aorta. The findings presented in this paper validate the necessity of FBN1 gene testing in all individuals presenting with isolated EL. As we observed, these individuals are at increased risk of cardiovascular complications. Furthermore, we also noted that the majority of our patient cohort's mutations occurred in the 5' portion of the FBN1 gene, and were found to affect highly conserved cysteine residues, which may indicate a possible genotype-phenotype correlation. We conclude that in patients with isolated features of EL, FBN1 mutation analysis is necessary to aid in providing prompt diagnosis, and to identify patients at risk for potentially life-threatening complications. Additionally, knowledge of the type and location of an FBN1 mutation may be useful in providing further clinical correlation regarding phenotypic progression and appropriate medical management.

Marfan Syndrome, an autosomal dominant, generalized disorder affecting the connective tissue, caused by mutations of FBN 1 gene which leads to deficiency of fibrillin 1 leading to reduced microfibril formation and disrupts the mechanical integrity of connective tissue, presents a complex clinical picture affecting multiple systems, poses significant challenges to conventional management. We present an 18-year-old female with Marfan Syndrome, highlighting her clinical features such as thin and slender body with disproportionately long arms and legs as compared with the trunk, bilateral Ectopia lentis, Arachnodactyly, positive Walker Murdoch Wrist sign and positive Steinberg Thumb sign, bilateral Pes planus, asymmetrical chest with mild Pectus carinatum deformity and moderate degree of Kyphoscoliosis along with winging of scapula. This article explores the Ayurvedic concept of Beeja dosha and highlights the value of integrating Ayurvedic insights into the management of Marfan Syndrome, offering a holistic and personalized approach to patient care to improve the quality of life and aims to deepen understanding of Marfan Syndrome from an Ayurvedic perspective, laying the groundwork for future research into Ayurvedic management strategies.

A rare case of bilateral ectopia lentis with isolated lens coloboma in Marfan syndrome is reported. A 21-year-old female presented with decreased vision in both eyes. Her unaided visual acuity was 20/200 and 20/400 in the right and left eye, respectively, improving to 20/40 with –4.5 DS/–3.0 DC x 10° correction in the right eye and 20/80 with –10.0 DS/–6.5 Dc x10° correction in the left eye. On slit lamp examination under mydriasis, both eyes revealed ectopia lentis with lens coloboma and stretched zonules. Fundus examination revealed pigmentary changes at the fovea. On systemic evaluation, she was diagnosed with Marfan syndrome. She was prescribed a refractive correction in form of a contact lens and kept under observation.

Functional and Structural Outcomes Following Lensectomy for Ectopia Lentis

Marfan syndrome is named after the French pediatrician Antoine Bernard-Jean Marfan who described in 1896 a girl with arachnodactyly and long limbs1. The patient also had congenital contractures of the elbows and would not fulfill the current criteria for Marfan syndrome. She probably was suffering from a condition that we now call contractural arachnodactyly, caused by mutations in the FBN2 gene.The clinical features of Marfan syndrome affect many systems of the body. The most obvious are the skeletal features, long limbs, tall stature, long thin fingers (arachnodactyly or spider fingers). The skeletal features can be scored objectively as: arm span more than 1.05 x body length; wrist sign (thumb and index finger can encircle the wrist of the other hand with at least one digit overlap) and thumb sign (when making a fist around the thumb, one digit of the thumb sticks out). The main neurological symptom is dural ectasias. The most severe symptoms are cardiovascular: mitralis valve prolapse, aortic dilatation and thoracic aortic aneurysms and dissections, which may lead to sudden death5. However, I noticed in discussions with patients that they often consider the ocular symptoms, severe myopia and lens luxation, the worst for themselves, because the latter may lead to blindness.

Marfan syndrome is a potentially fatal disorder with cardiovascular, skeletal, and other manifestations that may also be seen in individuals without Marfan syndrome, making diagnosis difficult. Our goals were (1) to examine the ways in which patients have been recognized as having Marfan syndrome, (2) to examine the prevalence of current diagnostic findings, and (3) to determine which physically evident features are most sensitive and specific for referral to confirm a diagnosis of Marfan syndrome. Between 2005 and 2007, we prospectively studied 183 consecutive patients with identified Marfan syndrome (Marfan group) and 1257 orthopaedic patients and family members (non-Marfan group). For the Marfan group, we recorded age at the time of recognition and the methods by which the syndrome was recognized; we used Ghent criteria to identify physically and radiographically evident features. For the non-Marfan group, we examined for Ghent criteria that could be noted on the basis of a routine history, physical examination, or radiographs. We used means, odds ratios, and frequencies to analyze the diagnostic use of each finding (alpha = 0.05). According to the Ghent criteria, 27% of patients in the Marfan group (mean age at the time of diagnosis, 7.3 years) had major skeletal involvement whereas 19% had zero or one skeletal feature. The most common physical features were craniofacial characteristics, high-arched palate, positive thumb and wrist signs, and scoliosis. In the non-Marfan group, 83% had one skeletal feature, 13% had two skeletal features, and 4% had three skeletal features or more. The physical features with the highest diagnostic yield were craniofacial characteristics, thumb and wrist signs, pectus excavatum, and severe hindfoot valgus. Musculoskeletal clinicians should be aware of the diagnostic features of Marfan syndrome. Patients with three to four physically evident features, or two highly specific features (e.g., thumb and wrist signs, craniofacial features, dural ectasia, or protrusio), should be carefully reexamined and possibly referred for an echocardiogram or a genetics consultation. Diagnostic Level II. See Instructions to Authors for a complete description of levels of evidence.