Down syndrome: Possible predisposition to retinoblastoma

Abstract

Recent studies reviewing the pattern of malignant disorders in individuals with Down syndrome (DS) suggests an association between DS and retinoblastoma (RB) [1][2][3]. We encountered such a patient: retinoblastoma in a young child with DS, and here discuss the possible link between both diseases.Our patient was a 20-month-old girl with trisomy 21 who was referred to the Ocular Oncology Unit for a suspected right intraocular tumour. She was the first child of young parents and had a history of complex cardiac malformation (atrioventricular defect and tetralogy of Fallot) that had previously been corrected. A comprehensive ocular examination under anesthesia was performed and revealed a right 12 mm  11 mm  5 mm retinal tumoral mass located 1 mm inferior to the papilla; no vitreous or subretinal seeding was detected and examination of the left eye was normal. Metastatic evaluation including cerebral magnetic resonance imaging was negative. The diagnosis of unilateral sporadic RB (Reese-Ellsworth group III) was confirmed and the child was treated with chemoreduction (6 cycles of carboplatin, vincristine, etoposide) as previously described [4] and five sessions of transpupillary thermotherapy. The patient is still well without recurrence 18 months after the last local treatment. Genetic analysis by sequencing confirmed the absence of constitutional alteration of the RB gene in this patient. DISCUSSIONWith this patient, 16 cases of RB in children with DS have been described in the literature [5][6][7][8][9][10][11][12][13][14]. In addition to two large epidemiologic studies conducted in Norway and Denmark, it provides further evidence of a possible association between DS and RB [15,16].The pattern of occurrence of malignant disorders in patients with DS is unique: the risk of leukemia is 20-fold higher in DS than in non DS whereas malignant solid tumours seem to be globally underrepresented as compared with the general population [1]. However, among these solid tumours, some are in excess including lymphomas, germ cell tumours (gonadal and extragonadal), and possibly RB [3]. Neoplasms in DS patients are seen at a younger age, sometimes in fetal life (leukemias and testicular germ cell tumours) or neonatally (leukemias and lymphomas). By contrast, other tumours are rarely seen in patients with DS, particularly neuroblastomas and nephroblastomas in young children or intracranial and peripheral nerve tumours [1,3,5]. These observations suggest that in DS, some tissues are more affected by malignant diseases; e.g., hematopoietic elementsf or germ cells and others seem to be protected. This evidence supports the hypothesis there are leukaemogenic genes and several tumour suppressor genes on chromosome 21 [3,17]. Another specific tumour profile in DS is the marked preponderance of affected males by malignant diseases and the decreased risk of secondary cancers [1].Among the 16 reported cases of RB associated with DS, a high male sex ratio of 2.5:1 is also observed (10 males; 4 females; 2 unknown). Five of the 16 patients ...

Down syndrome: a review of ocular manifestations

“…However, several isolated reports of retinoblastoma in patients with Down syndrome have suggested a predisposition to the condition, though no population-based studies have been performed. [132][133][134][135] There are two documented cases of rare pigment epithelium neoplasm developing on the same tissue of the eye -one bilateral case in an 11-year-old and one aggressive unilateral case in a 37-year-old patient. Both were found to have areas of focal hyperplasia of the retinal pigment epithelium, alluding to the possible vulnerability of the retinal pigment epithelium to an overgrowth in Down syndrome patients.…”

The Impact of Optical Factors on Resolution Acuity in Children with Down Syndrome

“…20 -24 A few case studies cite instances of optic disc elevation, 25,26 macular coloboma, 27 Leber congenital amaurosis, 28 and a possible link between DS and retinoblastoma. 29,30 There is also evidence of increased vasculature at the optic nerve head. 23,[31][32][33] No studies have been published regarding retinal function in DS using techniques such as electroretinograms.…”