Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings

Abstract

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin‐C‐induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X‐ray‐induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid‐type aberrations. She had a number of typical clinical features, including cafe‐au‐lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelo‐dysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin‐C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous ‘butterfly rash’. Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

Non-ocular tumours following retinoblastoma in Great Britain 1951 to 2004

“…There were 13 tumours in 13 non-heritable cases; one of these was a case of acute myeloid leukaemia that developed in a child with Fanconi anaemia: details of this child have been published in a previous paper;6 it is well known that there is an increased incidence of leukaemia associated with this condition.…”

Fanconi anaemia with bilateral diffuse pulmonary arterio venous fistulae: a case report

“…Apart from squamous cell carcinomas, FA is also associated with liver tumours [18] and focal nodular hyperplasia of liver [19]. Other malignancies linked with FA include; Wilms' tumour, medulloblastoma [20] and retinoblastoma [21]. …”

Ocular manifestations and visual functions in patients with Fanconi anaemia

“…Isolated case reports have described congenital glaucoma (Aslan et al 2005), cataract (Elgohary et al 2006), uveal or optic disc vasculopathy (Yahia et al 2006;Jain et al 2007) and retinoblastoma (Gibbons et al 1995).…”

“…Ocular manifestations, reported in almost half (48%) of 419 patients in the International Fanconi Anaemia Registry, were short and ⁄ or almondshaped palpebral fissures, hyper-or hypotelorism, ptosis, microphthalmia and epicanthal folds (Giampietro et al 1997). Isolated case reports have described congenital glaucoma (Aslan et al 2005), cataract (Elgohary et al 2006), uveal or optic disc vasculopathy (Yahia et al 2006;Jain et al 2007) and retinoblastoma (Gibbons et al 1995).…”