Ocular findings in Loeys-Dietz syndrome

Busch, Catharina; Voitl, Robert; Goergen, Barbara; Żemojtel, Tomasz; Gehle, Petra; Salchow, Daniel J.

doi:10.1136/bjophthalmol-2017-311254

Cited by 18 publications

(29 citation statements)

References 17 publications

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“…Mutations in Tgf‐β pathway components, including TGFBR1 (OMIM 190181), TGFBR2 (OMIM 190182), TGFB2 (OMIM 190220) and SMAD3 (OMIM 603190), have been linked to Loeys‐Dietz syndrome, a disorder affecting the connective tissue and cardiovascular systems (Loeys et al, 2005; Loeys et al, 2006). Although craniofacial defects are common in this syndrome, microphthalmia, anophthalmia, and coloboma have not been reported (Busch et al, 2018). Studies utilizing transgenic zebrafish reporter lines show active Tgf‐β signaling in the fissure, and many components of the Tgf‐β signaling pathway are expressed in periocular tissues, including the signaling ligands Tgfb2, Tgfb3, and their receptor Tgfbr2b (Knickmeyer et al, 2018).…”

Section: Ventral Head Mesenchyme and Extracellular Matrix Remodelingmentioning

confidence: 99%

“…(Loeys et al, 2005;Loeys et al, 2006). Although craniofacial defects are common in this syndrome, microphthalmia, anophthalmia, and coloboma have not been reported (Busch et al, 2018). Studies utilizing transgenic zebrafish reporter lines show active Tgf-β signaling in the fissure, and many components of the Tgf-β signaling pathway are expressed in periocular tissues, including the signaling ligands Tgfb2, Tgfb3, and their receptor Tgfbr2b (Knickmeyer et al, 2018).…”

Section: Ventral Head Mesenchyme and Extracellular Matrix Remodelingmentioning

confidence: 99%

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Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Yoon

Fox

Dicipulo

et al. 2020

American J of Med Genetics Pt C

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Ocular coloboma is a congenital disorder of the eye where a gap exists in the inferior retina, lens, iris, or optic nerve tissue. With a prevalence of 2-19 per 100,000 live births, coloboma, and microphthalmia, an associated ocular disorder, represent up to 10% of childhood blindness. It manifests due to the failure of choroid fissure closure during eye development, and it is a part of a spectrum of ocular disorders that include microphthalmia and anophthalmia. Use of genetic approaches from classical pedigree analyses to next generation sequencing has identified more than 40 loci that are associated with the causality of ocular coloboma. As we have expanded studies to include singleton cases, hereditability has been very challenging to prove. As such, researchers over the past 20 years, have unraveled the complex interrelationship amongst these 40 genes using vertebrate model organisms. Such research has greatly increased our understanding of eye development. These genes function to regulate initial specification of the eye field, migration of retinal precursors, patterning of the retina, neural crest cell biology, and activity of head mesoderm. This review will discuss the discovery of loci using patient data, their investigations in animal models, and the recent advances stemming from animal models that shed new light in patient diagnosis.

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Section: Ventral Head Mesenchyme and Extracellular Matrix Remodelingmentioning

confidence: 99%

Section: Ventral Head Mesenchyme and Extracellular Matrix Remodelingmentioning

confidence: 99%

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Yoon

Fox

Dicipulo

et al. 2020

American J of Med Genetics Pt C

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“…Loeys-Dietz Syndrome is an AD inherited disorder with mutations in TGF beta receptor 1 (TGFBR1), TGF beta receptor 2 (TGFBR2), TGF beta 2 (TGFB2), TGF beta 3 (TGFB3), or SMAD3 [10,50,66], with an estimated prevalence of ≤1 in 100,000 [51]. Systemic manifestations of LDS are similar to MFS, including vascular aneurysms (cerebral, thoracic, or ab-dominal), skeletal abnormalities (pectus excavatum or carinatum), scoliosis, joint laxity, and craniofacial abnormalities (cleft palate, craniosynostosis, or bifid uvula) [10]. Allergies, skin abnormalities, neurological findings, pulmonary manifestations, and pregnancy-related changes have also been reported [67,68].…”

Section: Loeys-dietz Syndromementioning

confidence: 99%

“…An initial study involving 14 patients with LDS noted 13 with hypertelorism, seven with exotropia, and eight with blue sclera [50]. However, another retrospective review found no patients with hypertelorism or blue/dusky sclera [10], making it challenging to confirm these findings as diagnostic criteria for LDS. Patients with LDS have decreased CCT and increased myopia rates compared to controls, though myopia was less common and severe compared to patients with MFS [10].…”

Section: Loeys-dietz Syndromementioning

confidence: 99%

“…However, the above risk factors may not be problematic for every person with an HDCT diagnosis. For example, reduced CCT is associated with specific gene sequence variants [3], and clinical presentation for each HDCT is variable and wide-ranging in symptom severity [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The exact rate of post-LASIK complications has been difficult to assess due to limited refractive surgery cases performed on those diagnosed with HDCTs.…”

Section: Introductionmentioning

confidence: 99%

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Controversy and Consideration of Refractive Surgery in Patients with Heritable Disorders of Connective Tissue

Moshirfar

Barke

Huynh

et al. 2021

JCM

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Heritable Disorders of Connective Tissue (HDCTs) are syndromes that disrupt connective tissue integrity. They include Osteogenesis Imperfecta (OI), Ehlers Danlos Syndrome (EDS), Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS), Epidermolysis Bullosa (EB), Stickler Syndrome (STL), Wagner Syndrome, and Pseudoxanthoma Elasticum (PXE). Because many patients with HDCTs have ocular symptoms, commonly myopia, they will often present to the clinic seeking refractive surgery. Currently, corrective measures are limited, as the FDA contraindicates laser-assisted in-situ keratomileusis (LASIK) in EDS and discourages the procedure in OI and MFS due to a theoretically increased risk of post-LASIK ectasia, poor wound healing, poor refractive predictability, underlying keratoconus, and globe rupture. While these disorders present with a wide range of ocular manifestations that are associated with an increased risk of post-LASIK complications (e.g., thinned corneas, ocular fragility, keratoconus, glaucoma, ectopia lentis, retinal detachment, angioid streaks, and ocular surface disease), their occurrence and severity are highly variable among patients. Therefore, an HDCT diagnosis should not warrant an immediate disqualification for refractive surgery. Patients with minimal ocular manifestations can consider LASIK. In contrast, those with preoperative signs of corneal thinning and ocular fragility may find the combination of collagen cross-linking (CXL) with either photorefractive keratotomy (PRK), small incision lenticule extraction (SMILE) or a phakic intraocular lens (pIOL) implant to be more suitable options. However, evidence of refractive surgery performed on patients with HDCTs is limited, and surgeons must fully inform patients of the unknown risks and complications before proceeding. This paper serves as a guideline for future studies to evaluate refractive surgery outcomes in patients with HDCTs.

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Ectopia lentis in Loeys‐Dietz syndrome type 4

Braverman

Blinder

Khanna

et al. 2020

American J of Med Genetics Pt A

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Loeys‐Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early‐onset and aggressive disease of the aorta and its branches. There are multiple types of Loeys‐Dietz syndrome related to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3. Individuals with Loeys‐Dietz syndrome may be misdiagnosed as having Marfan syndrome due to shared phenotypic features and aortic root dilation. However, ectopia lentis has been an important discriminating feature, being unique to Marfan syndrome and not reported to be associated with Loeys‐Dietz syndrome. We report the case of a 46‐year‐old woman with Loeys‐Dietz syndrome type 4 due to a pathogenic variant in TGFB2 who was diagnosed with ectopia lentis at age 44. The patient underwent whole exome sequencing and no other pathogenic variants were found to explain the ectopia lentis. Our findings indicate that ectopia lentis may be an uncommon finding in Loeys‐Dietz syndrome type 4 and emphasize the importance of genetic testing in familial thoracic aortic aneurysm disease.

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Ocular findings in Loeys-Dietz syndrome

Abstract: Ocular features of LDS include decreased central corneal thickness and mild myopia. Ectopia lentis may be slightly more common than in controls but appears less common than in Marfan syndrome. Hypertelorism, scleral and retinal vascular abnormalities were not features of LDS.

Cited by 18 publications

References 17 publications

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Controversy and Consideration of Refractive Surgery in Patients with Heritable Disorders of Connective Tissue

Ectopia lentis in Loeys‐Dietz syndrome type 4

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