Bloom syndrome is an archetypal “chromosome breakage syndrome.” A recessively inherited mutation in the BLM
gene leads to an inordinate frequency of chromosomal breaks and rearrangements, possibly via aberrant repair of breaks in double stranded DNA.7–10
mutation in turn gives rise throughout life to a high number of acquired somatic mutations. Genomic instability can affect virtually all genetic loci, cell types, and tissues in an individual with Bloom syndrome, so it is not surprising that manifold ocular abnormalities have been observed. As described here, a single patient in a short span of time displayed multiple independent retinal pathologies. In addition to early onset retinal drusen, which may be considered characteristic for the syndrome, he developed two different complications secondary to systemic diseases: diabetic retinopathy and leukaemic retinopathy.
Perhaps the most common ocular finding in Bloom syndrome is the presence of retinal drusen at an early age (fig 1); noted in this patient at age 39, drusen may be present even in childhood. In this and in other reported cases the drusen are hard, small, and non-confluent. Landau and colleagues11
first described bilateral drusen in three children and termed them “colloid body-like spots.” They equated these childhood drusen with those more commonly seen as a “senile phenomenon,” and indeed there is a clinical resemblance to age related macular degeneration. Of note, no form of exudative macular degeneration has been reported in these patients.
Non-proliferative diabetic retinopathy in this patient had typical features (fig 2), with severe macular oedema recalcitrant to standard laser therapy. Diabetes is a classic feature of Bloom syndrome, usually occurring in its non-insulin dependent form. It is therefore surprising that diabetic retinopathy has not, to our knowledge, previously been described in Bloom syndrome. This absence may result from patient age and diabetes duration being curtailed by early mortality in patients with Bloom syndrome. The patient reported here had reached 40 years of age, one of the longest surviving patients with Bloom syndrome; perhaps his later age and duration of diabetes allowed for retinal expression of his diabetes.
Acute leukaemias are the most frequent malignancies arising in patients with Bloom syndrome, but again leukaemic retinopathy has not to our knowledge been reported previously. In this case, rapid visual loss and haemorrhagic retinopathy were the presenting signs for the diagnosis of acute leukaemia. The retinal findings were those of typical leukaemic retinopathy12–13
with bilateral haemorrhages in the superficial and deep retina throughout the posterior pole, some white centred haemorrhages, and also subretinal haemorrhage at the central macula in one eye (fig 3). Partial reversal of the retinopathy was seen following chemotherapy and remission of his leukaemia.
A wide variety of other ocular abnormalities have been found in Bloom syndrome (see table 1). A sunlight induced telangiectatic facial rash resembling that of lupus erythematosis is one of the diagnostic features of the disease; telangiectatic lesions can involve the lower eyelids14
and have even been reported on the conjunctiva.15,16
In the patient described here, the anterior chamber angles were seen to be narrow bilaterally; he had no evidence of narrow angle glaucoma, and glaucoma has not been reported as a feature of Bloom syndrome.
Ophthalmological abnormalities reported in Bloom syndrome
Abnormalities of the posterior segment have been described sparsely in Bloom syndrome. Although a wide array of systemic diseases and malignancies appear in Bloom syndrome, retinal pathologies secondary to disorders such as diabetes, leukaemia, lymphoma, or tumour metastases have not been reported. Retinoblastoma has been reported in a child17
; an infant with bilateral optic nerve hypoplasia has also been reported.15
In conclusion, the collected observations in Bloom syndrome indicate that a wide variety of ocular abnormalities can arise as a consequence of excessive somatic mutations. While reports of retinal abnormalities have been scant in this disorder, the ophthalmological spectrum of Bloom syndrome can be expanded from the multiple, independent findings in this patient.