RETINAL VASCULAR TORTUOSITY IN DIGEORGE SYNDROME COMPLICATED BY SOLAR RETINOPATHY Jennifer E. De Niro, MD,* Sandeep Randhawa, MD,* H. Richard McDonald, MD*†

Purpose: To report a case of vascular tortuosity associated with DiGeorge syndrome that was complicated by solar retinopathy. Methods: Case report and literature review. Results: A 56-year-old woman with DiGeorge syndrome with secondary schizophrenia and developmental delay presented with decreased vision that was worse in her left eye. Ocular examination revealed bilateral retinal vascular tortuosity involving both the arteries and veins. Both eyes had an abnormal foveal light reflex with a central yellowish hue, which was more pronounced in the left eye. Optical coherence tomography showed disruption of the photoreceptor inner segment–outer segment junction and retinal pigment epithelium centrally, which was also more prominent in the left eye. Conclusion: DiGeorge syndrome is associated with retinal vascular tortuosity in a large percentage of patients. The patient’s decreased vision is likely caused by solar retinopathy (prolonged sun gazing as a result of the secondary schizophrenia and developmental delay). RETINAL CASES & BRIEF REPORTS 7:343–346, 2013

visual acuity was 20/32 in the right eye and 20/50 in the left eye. The intraocular pressure was within normal limits in both the eyes, and the anterior segment examination was unremarkable. Dilated fundus examination revealed bilateral vascular tortuosity involving both the arterioles and the venules (Figure 1). The fovea in both eyes had a yellowish discoloration. Fluorescein angiography did not show any retinal vascular leakage or evidence of vasculitis or optic nerve head inflammation (Figure 2). Spectral-domain optical coherence tomography showed disruption of the photoreceptor inner segment–outer segment junction and retinal pigment epithelium that was more prominent in the left eye (Figure 3). In addition to DiGeorge syndrome, the patient’s medical history was notable for developmental delay, schizophrenia, diabetes mellitus, obstructive sleep apnea, mild pulmonary hypertension, hypothyroidism, sensorineural hearing loss, unilateral right club foot, and a right-sided aortic arch, which were all related to the DiGeorge syndrome. Her most recent hemoglobin A1c level was 6.3. She also had a history of hyperprolactinemia, which was attributed to risperidone. On physical examination, she had dysmorphic appearance of nose and ears secondary to DiGeorge syndrome.

From the *Department of Ophthalmology, California Pacific Medical Center, San Francisco, California; and †West Coast Retina Medical Group, San Francisco, California.

T

he causes of retinal vascular tortuosity are extensive and are thought of in terms of generalized tortuosity (arterial and venous), predominantly venous or predominantly arterial tortuosity, conditions that produce retinal ischemia, and rare etiologies of increased toruosity, which includes DiGeorge syndrome. We present a case of DiGeorge syndrome complicated by solar retinopathy as a result of sun gazing.

Case Report A 56-year-old woman with DiGeorge syndrome presented with decreased vision that was worse in her left eye. Her best-corrected Supported by the San Francisco Retina foundation and Pacific Vision Foundation. None of the authors have any financial/conflicting interests to disclose. Reprint requests: H. Richard McDonald, MD, West Coast Retina, 185 Berry Street, Suite 130, San Francisco, CA 94107; e-mail: [email protected]

Discussion The differential diagnosis of retinal vascular tortuosity is extensive. Causes of generalized tortuosity (arterial and venous) include hyperopia, retinopathy of 343

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Fig. 1. Color fundus photographs showing bilateral vascular tortuosity. A yellow dot is also present in the central fovea bilaterally but is more prominent in the left eye.

prematurity, and epiretinal membranes. Predominantly, venous tortuosity may arise from venous congestion caused by hyperviscosity syndromes, cardiopulmonary disease, pseudotumor cerebri, or retinal vein occlusions. Conditions that produce retinal ischemia, including diabetic retinopathy and high-altitude retinopathy, may also lead to venous tortuosity. Fetal alcohol syndrome has also been associated with venous tortuosity. Predominantly, arterial tortuosity may be caused by an increased blood flow because of a wide range of conditions, including aortic coarctation, anemia, sickle cell retinopathy, carotid cavernous sinus fistula, localized feeder vessels from tumors, Coats disease, and Von Hippel–Lindau

Fig. 2. Fluorescein angiography did not show any retinal vascular leakage or evidence of vasculitis or optic nerve head inflammation.

disease.1 The syndrome of idiopathic retinal vasculitis, aneurysms, and neuroretinitis is associated with vascular tortuosity.2 Rare etiologies of increased retinal tortuosity include familial retinal arteriolar tortuosity, Osler–Weber–Rendu syndrome, Aarskog syndrome, Wyburn–Mason syndrome, neurofibromatosis Type 1, fascioscapulohumeral muscular dystrophy, Fabry disease, and DiGeorge syndorme.1,3 Wyburn–Mason syndrome is a phakomatoses defined by unilateral arteriovenous malformations that affect the retina, brain, and subcutaneous facial structures. It is nonhereditary and has no sex predilection. Patients with retinal arteriovenous malformations warrant neuroimaging to exclude concomitant intracranial involvement.4

DIGEORGE SYNDROME WITH SOLAR RETINOPATHY

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Fig. 3. Spectral-domain optical coherence tomography showing disruption of the photoreceptor inner segment–outer segment junction and retinal pigment epithelium (more prominent in the left eye).

Familial retinal artery tortuosity is a rare disorder with autosomal dominant inheritance characterized by progressive, pronounced tortuosity of the second-order and third-order arterioles in the macular and peripapillary area. The vascular tortuosity generally develops during childhood or early adulthood and can be complicated by intra- or preretinal hemorrhages. The hemorrhages generally clear with time, usually with recovery of full visual acuity.1 Children with fetal alcohol syndrome experience growth retardation, mental deficiency, and characteristic facial dysmorphism, including microcephaly, microphthalmia, and/or short palpebral fissures, poorly developed philtrum, and flattening of the maxillary area. Tortuosity of the retinal vessels, especially the arteries, occurs in up to 49% of patients. Patients frequently have optic nerve hypoplasia, and visual acuity is often moderately to severely reduced.5 The syndrome of idiopathic retinal vasculitis, aneurysms, and neuroretinitis typically affects young, healthy individuals and is not associated with any systemic abnormalities. Patients have optic nerve head vascular tortuosity and numerous aneurysmal dilations of the retinal and optic nerve head arterioles either at or near the major branching sites. These vascular malformations have a propensity to leak fluid, which causes a visually threatening exudative retinopathy in almost all patients. Extensive peripheral capillary nonperfusion is another very common manifestation. The majority of patients have vitritis, and many have anterior uveitis. On fluorescein angiography, patients characteristically have neuroretinitis and retinal vasculitis.2

Fabry disease is an X-linked inborn error of glycosphingolipid metabolism. The clinical features include paresthesias of the extremities, cutaneous angiokeratomas, renal failure, and ischemic complications involving the heart or brain. Conjunctival and retinal vascular tortuosity and corneal verticillata are frequently observed. The retinal tortuosity affects both arteries and veins. Visual acuity is not affected.6 Aarskog syndrome (facio-digital-genital dysplasia) is an X-linked genetic disorder characterized by short stature, dysmorphic facies with telecanthus and hypertelorism, shawl scrotum, and digital anomalies. It is associated with bilateral venous tortuosity and optic nerve hypoplasia.7 DiGeorge syndrome (Chromosome 22q11.2 deletion syndrome, velocardiofacial syndrome) occurs in approximately 1:4,000 births. The majority of patients have a cardiac anomaly (49–83%), and many patients have mild to moderate immune deficiency. Additional features include endocrine abnormalities (hypocalcemia 4%, hypoparathyroidism 17–60%, and diabetes), renal anomalies (up to 37%), palatal defects (up to 80%), hearing loss (10% sensorineural, 45% conductive), lower limb anomalies (up to 15%), developmental delay (up to 75%), and psychiatric disorders.8,9 Although phenotypic variability occurs, individuals with DiGeorge syndrome have high rates (up to 30%) of psychiatric disorder, especially schizophrenia (with molecular genetic studies suggesting that a schizophrenia susceptibility locus maps to Chromosome 22q).10,11 Accurate phenotypical evaluation of patients with Del22 demonstrates

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that facial anomalies, severely or mildly expressed, are detectable in all subjects. Characteristic facial features include periorbital fullness, narrow upslanted palpebral fissures, prominent nose with large tip, and hypoplastic nares, small mouth with everted upper lip, and small dysmorphic ears. Some patients, especially children, may have only a subtle facial phenotype.12 The dysmorphic facial features including a bulbous nasal tip, micrognathia, and small ears were also seen in our patient.3 Ophthalmologic examination has shown posterior embryotoxon in 49% of patients and tortuous retinal vessels in 34% to 75% of patients.3,13 The presence of retinal vascular tortuosity in our patient (Figure 1) and her right-sided aortic arch, schizophrenia, developmental delay, hearing loss, and dysmorphic facial features are all consistent with DiGeorge syndrome. Patients with DiGeorge syndrome have a high incidence of refractive error, but their bestcorrected visual acuity is generally within the normal limits.3 Our patient’s examination and imaging findings are most consistent with solar retinopathy, which is a photochemical retinal injury caused by staring directly at the sun. Solar retinopathy has been described to occur in patients with psychiatric illness.14 Patients may complain of a central scotoma or may be asymptomatic. The ophthalmoscopic signs of solar retinopathy are limited to the fovea. In the acute stage, there is a yellow spot in the fovea. In long-standing solar retinopathy, there is a small multifaceted outer retinal hole. These holes can be mistaken for small, full-thickness macular holes because of their reddish center. However, on closer inspection, the holes are restricted to the outer retina stereoscopically. Their borders are usually irregular and often have a multifaceted (angulated) appearance, as opposed to the round or oval appearance of full-thickness macular holes. Spectral-domain optical coherence tomography demonstrates a defect in the outer retina at the fovea involving the photoreceptor inner segment–outer segment junction and the retinal pigment epithelium, as seen in our patient (Figure 3). Many patients lack visible retinal pigment epithelial changes, but severe solar retinopathy can produce significant retinal pigment epithelial disruption. Asymmetric and unilateral findings have been described in solar retinopathy, most frequently being worse in the dominant eye.15

This case highlights the presence of retinal vascular tortuosity as an important ocular finding in DiGeorge syndrome. Given the association with schizophrenia and psychosis, this patient is also predisposed to solar retinopathy as a result of sun gazing. Key words: Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome, retinal vascular tortuosity, solar retinopathy. References 1. Sutter FKP, Helbig H. Familial retinal arteriolar tortuosity: a review. Surv Ophthalmol 2003;48:245–255. 2. Chang TS, Aylward W, Davis JL, et al. Idiopathic retinal vasculitis, aneurysms, and neuro-retinitis. Ophthalmology 1995; 102:1089–1097. 3. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine 2011;90:1–18. 4. Chan W-M, Yip NKF, Lam DSC. Wyburn-Mason syndrome. Neurology 2004;62:99. 5. Strömland K. Ocular involvement in the fetal alcohol syndrome. Surv Ophthalmol 1986;31:277–284. 6. Nguyen TT, Gin T, Nicholls K, et al. Ophthalmological manifestations of Fabry disease: a survey of patients at the Royal Melbourne Fabry Disease Treatment Centre. Clin Experiment Ophthalmol 2005;33:164–168. 7. Jogiya A, Sandy C. Mild optic nerve hypoplasia with retinal venous tortuosity in Aarskog (facial-digital-genital) syndrome. Ophthalmic Genetics 2005;26:139–141. 8. Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370:1443–1452. 9. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 deletion syndrome. . In: Pagon RA, Bird TD, Dolan CR, et al, eds. GeneReviews™ [Internet]. Seattle, WA: University of Washington; 1993. Available at: http://www.ncbi.nlm.nih.gov/ books/NBK1523/. Accessed April 1, 2013. 10. Murphy KC. Schizophrenia and velo-cardio-facial syndrome. Lancet 2002;359:426–430. 11. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56:940–945. 12. Digilio MC, Marino B, Capolino R, Dallapiccola B. Clinical manifestations of deletion 22q11.2 syndrome (DiGeorge/velocardio-facial syndrome). Images Paediatr Cardiol 2005;7:23–34. 13. Casteels I, Casaer P, Gewillig M, et al. Ocular findings in children with microdeletion in chromosome 22q11.2. Eur J Pediatr 2008;167:751–755. 14. Anaclerio AM, Wicker HS. Self-induced solar retinopathy by patients in a psychiatric hospital. Am J Ophthalmol 1970;69: 731–736. 15. Comander J, Gardiner M, Loewenstein J. High-resolution optical coherence tomography findings in solar maculopathy and the differential diagnosis of outer retinal holes. Am J Ophthalmol 2011;152:413–419.

Retinal vascular tortuosity in DiGeorge syndrome complicated by solar retinopathy.

To report a case of vascular tortuosity associated with DiGeorge syndrome that was complicated by solar retinopathy...
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