Ehler -Danlos syndrome Type IV (EDS Type IV) results from mutations in the COL3A1 gene, which encodes chains of type III procollagen. Patients with EDS Type IV have typical features like thin translucent skin with a tendency for easy bruising, typical facial appearance, acrogeria, hypermobility of joints, and arterial, intestinal, or uterine fragility or rupture. Glaucoma is a seldom reported finding in a case of EDS Type IV. We report a case of advanced glaucoma in a patient with typical features of EDS Type IV.
A 26-year-old male presented with the complaint of defective vision in the left eye. He was a known myope on refractive correction since childhood. He noticed dimness of vision in the right eye seven years ago, which has gradually progressed [Figs. 1 and 2]. His best corrected visual acuity (BCVA) was hand movement (HM) in the right eye and 6/60, improving to 6/9 with -4.00 diopter sphere and -0.25 diopter cylinder at 180°(-4.00/-0.25 × 180) in the left eye. Lid examination showed ptosis and ectropion in both eyes [Figs. 3a and b]. Fornices showed congestion with papillae in both eyes. Right eye anterior segment examination showed a relative afferent pupillary defect (RAPD). Left eye examination was normal. Intraocular pressure (IOP) in the right and left eyes were 46 and 42 mmHg, respectively. Gonioscopy showed open angles in both eyes [Grade IV Shaffer's in all quadrants]. Fundus examination showed glaucomatous optic atrophy (GOA) in right eye and a cup disc ratio of 0.75 with bipolar rim thinning with pallor of the neuroretinal rim in the left eye [Fig 4a and b]. Central corneal thickness (CCT) was 588 μ and 576 μ in right and left eye, respectively. Visual field of left eye was not reliable in spite of repeat tests, due to high false negative errors.
Systemic examination showed hyperextensible skin and joints. Hypermobility of the finger joints was present since childhood, and he had a tendency for skin-splitting. Acrogeria-an aged appearance in the extremities, particularly the hands-was apparent. He provided a history of easy bruising and tendency to fall easily, with two episodes of shoulder dislocation in the past. There was no family history of EDS. He had a hematoma in his right leg at presentation along with varicose veins in both legs. He had hypodontia, high arched palate, and history of delayed eruption of teeth. He also had skeletal abnormalities [Figs. 5–7]. He provided a history of having an intestinal rupture 5 years ago for which he had undergone surgery. These features were suggestive of EDS Type IV.
A diagnosis of open angle glaucoma in a case of EDS Type IV was made. He was referred to a rheumatologist. A decision to perform a trabeculectomy in the left eye first was made and done followed by a palliative trabeculectomy in the right eye [Figs. 8a and b]. Ectropion correction by horizontal lid tightening and lower-lid retractor reinsertion was done for both eyes. At the last follow up (3 years after trabeculectomy in the right eye) IOP was 14 and 12 mmHg in the right and left eye, respectively.
EDS is a clinically and genetically heterogeneous connective tissue disorder affecting as many as 1 in 5,000 individuals. EDS is characterized by abnormal collagen synthesis, affecting skin, ligaments, joints, blood vessels, and other organs. Following the identification of specific mutations in the genes the EDS classification scheme was condensed into six distinct clinical syndromes. Each subtype is based on the severity of clinical symptoms, pattern of inheritance, and the underlying genetic defect [Table 1]. All these gene mutations for specific subtypes of EDS involve the synthesis of collagen, collagen-modifying proteins or enzymes, and tenascin-X.
EDS Type IV is generally inherited in an autosomal dominant (AD) fashion, but autosomal recessive (AR) inheritance has also been reported. It is a very serious vascular disorder and not just a skin disease. Major complications of EDS Type IV are arterial, bowel, and uterine rupture. Reduced life expectancy is not generally a feature of EDS, with the exception of this vascular form (EDS Type IV). Median life expectancy for patients with EDS Type IV is 50 years because medium-sized arteries, the GI tract, and other organs tend to spontaneously rupture. Morbidity in EDS Type IV is due to dislocations, pain, or both from chronic joint laxity as well as aberrant scarring and wound healing from abnormal tensile strength of the skin. Various skeletal abnormalities described in EDS Type IV include micrognathia, club foot, congenital dislocation of hip, pectus excavatum, acroosteolysis, and joint contractures. Our patient was referred to a rheumatologist for his systemic problems and was confirmed to be a patient of EDS Type IV.
Major ocular complications are very infrequent in EDS. These patients have been commonly reported to have redundant skin on the upper eyelids, ease of eversion of the upper lid (Metenier's sign), and widely-spaced eyes. Other features like epicanthic folds and blueness of the sclera, strabismus, and myopia are less frequently encountered. Keratoconus, ectopia lentis, postoperative dehiscence of cataract wounds, and bilateral corneal lacerations as a result of minor trauma have been observed. Blue sclera, microcornea, and glaucoma were observed in a patient reported by Durham.
There have been very few reports of grave ocular complications in EDS Type IV patients and very few authors have reported association of glaucoma with EDS Type IV. Pollack et al., reported a case of recurrent carotid cavernous fistula (CCF) with secondary glaucoma and cerebral aneurysm in a case of EDS Type IV. Akar et al., reported a rare case of EDS Type IV with open angle glaucoma and skeletal abnormalities. Thus, although ocular abnormalities have been reported in some patients with EDS (including EDS Type IV), the association of glaucoma in a case of EDS Type IV has very rarely been reported in literature.
EDS Type IV patients have a Type III procollagen defect. The features of EDS Type IV results from mutations in the COL3A1 gene, which encodes the chains of type III procollagen. COL3A1 cause variable clinical phenotypes including acrogeria and vascular rupture. The corneoscleral and uveal trabecular meshwork is composed of Type I, II, and IV collagen, while the Juxtacanalicular Meshwork (JCM) has Types I, III, IV, V, and VI collagen. The Schlemms canal also has Type III collagen. Since EDS Type IV has the defect in the Type III procollagen, these patients have a propensity to develop an open angle glaucoma although very few cases have been reported in literature. The management of glaucoma in EDS Type IV has not been specified. Our patient had GOA in the right eye and advanced cupping in the left eye; therefore, we opted for surgical intervention.
This case report presents the extremely rare association of glaucoma in a case of EDS Type IV. The theories of pathogenesis and possible relationship between the syndrome and a defect in the ocular collagen have been established. Ophthalmologists should be aware of the ocular manifestations, hazards in clinical management, and possible significance of this syndrome in the study of the pathogenesis of glaucoma.
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Conflict of Interest: None declared.