Coats Disease and VATER Association in a 5-Year-Old Boy

Coats disease is an uncommon exudative retinopathy of unknown originthat may cause blindness. We report the unusual occurrence of Coats diseasein a 5-year-old boy with multiple congenital abnormalities due to VATER association.The possibility of a genetic basis for some cases of Coats disease is discussed.

The VATER association comprises congenital defects including vertebraldefects, imperforate anus, tracheoesophageal fistula, and radial and renaldysplasia.¹ The underlying cause of VATERassociation may be a severe embryonic insult during the simultaneous developmentof the organ systems.¹ Patients with VATERassociation often require multiple surgical procedures and extensive rehabilitation.We report a unique case of exudative retinopathy (Coats disease) in a caseof VATER association.

A child with a normal prenatal ultrasound at 20 weeks gestation anda negative TORCH (toxoplasmosis, other infections, rubella, cytomegalovirusinfection, and herpes simplex) panel was born after an otherwise uncomplicatedpregnancy by normal spontaneous vaginal delivery at 33 weeks gestational age.The results of a physical examination at birth revealed an imperforate anusand polydactyly with an extra digit lateral to the right thumb. The resultsof a radiological examination showed communicating hydrocephalus with gradeII bilateral renal reflux and hemivertebra with severe scoliosis (Figure 1A. Corrective surgical proceduresincluded digit amputation, colostomy, and anoplasty. There was no family historyof eye or genetic defects, and karyotyping was normal in the child and hisparents.

At 5 years of age, the patient was referred for left eye leukocoria.Visual acuity was 20/20 OD and 1/60 OS. There was total exudative retinaldetachment with associated tortuous vessels with multiple aneurysmal dilatationscompatible with Coats disease, stage 3B (Figure 1B.² The lower 2 quadrantsof the retina were preferentially affected. There was no evidence of associatedanterior chamber or vitreal inflammation. The findings of the retinal examinationof the fellow eye, including the periphery area, were normal. Further examinationof old photographs showed the patient had had leukocoria since the age of6 months. The results of B-scan ultrasonography revealed retinal detachmentwith no calcification or mass. This was confirmed by a computed tomographyscan of the orbits. Intraocular pressure was normal with no evidence of neovascularizationof the iris. Cryotherapy was offered to the patient to preserve vision andprevent further complications, including neovascular glaucoma, a painful blindeye, and a possible need for enucleation. The parents finally opted for conservativetreatment.

A number of patients with VATER association have been described as havingeye defects.¹ The most common associationsare coloboma and microphthalmos.³ However,the retina and posterior segment are seldom involved, and Coats disease washitherto unreported. The term Coats disease refersto idiopathic retinal telangiectasia with intraretinal or subretinal exudationand without appreciable signs of retinal or vitreal traction. The diagnosisof Coats disease is one of exclusion after careful workup and examination,especially with regard to retinoblastoma, retinopathy of prematurity, retinalcapillary angiomatosis, and toxocara, all of which were not implicated inour case. Reported associations include renal-retinal abnormalities and retinaldisorders.⁴ Familial forms exist, but nospecific gene defect is known. In the largest reported series, the medianage of diagnosis was 5 years with a male predominance (76%), the majoritywith unilateral disease (95%).² Aggressivemanagement for early cases, including laser photocoagulation, cryotherapy,and drainage of subretinal exudates using pars plana vitrectomy techniques,may prevent neovascular glaucoma and a painful blind eye.

Because the definitive genetic defects for both VATER association andCoats disease in humans are unknown, we can only speculate about the possiblecommon genetic link. Recently, an adriamycin-induced rat model of the VATERassociation, with defects in the hedgehog gene pathway, has been developed.⁵ The secreted glycoprotein, sonic hedgehog (SHH), acts as an endodermal signal that controls gut andlung patterning. Interestingly, the SHH protein isalso secreted by retinal ganglion cells to help optic disc astrocyte precursorcells to guide retinal axon growth, and to convert optic stalk neuroepithelialcells into pigmented cells. Both VATER and retinal defects can be producedby targeted SHH mutations. Ultrastructural retinalcell abnormalities are not infrequently found in pathologically examined eyesof patients with Coats disease.⁶ Nevertheless,it remains to be elucidated whether any aberrations in these pathways mayexplain the unusual clustering of specific defects in our case.

The authors have no relevant financial interest in this article.

Correspondence: Dr Hon, Department of Ophthalmology, Prince of WalesHospital, Shatin, Hong Kong (honc@ha.org.hk).