Diagnosis and Diagnostic Aids

The diagnosis of retinal AVM is essentially clinical, but fluorescein angiographic studies can be utilized to document the vascular pattern. The intracranial AVM is best imaged by magnetic resonance imaging or arteriography.

Treatment

Unlike the intracranial AVM, retinal AVMs are relatively stable and do not tend to bleed. Some lesions may lead to vascular occlusions and retinal ischemia with the development of neovascular glaucoma. If neovascular glaucoma occurs, symptomatic treatment can be offered. Intracranial AVMs are often not amenable to surgical resection because of their location in the midbrain. Embolization may be effective in these cases.

7.6.9  Ataxia Telangiectasia

7.6.9.1  Introduction

Although AT is included in phakomatoses, it has only limited similarity to other disorders in this group. AT has predominant neural, ocular, and cutaneous manifestations, but lacks dominant inheritance and tendency for systemic hamartomatosis. AT is a childhood neuro-degenerative disorder associated with ocular and cutaneous telangiectasia and immune dysfunction.

7.6.9.2  Historical Context

Madame Louis-Bar in 1941 described a young boy with progressive cerebellar ataxia and oculo-cutaneous telangiectasia [203]. The term AT was proposed by Boder and Sedgwick in 1958 when they described seven cases of familial progressive cerebellar ataxia, with oculo-cutaneous telangiectasia, and sinopulmonary infections [204]. Other features such as lymphoreticular malignancy and immune dysfunction were not reported until later [205].

7.6.9.3  Overview with Clinical Significance

AT is a rare autosomal recessive disorder with varied clinical manifestations. Ataxia is typically the first manifestations with onset by 5 years. In addition to some of the features outlined above, premature aging, chromosomal instability, and hypersensitivity to ionizing radiation are also important aspects of this disorder [206].

7.6.9.4  Classification

The AT phenotype is classified by studying the response of fibroblasts or lymphoblastoid cells to radiosensitivity. At least four different complementation groups have been identified. With the identification of a single AT gene, the exact role of complementation group has been questioned.

7.6.9.5  Genetics

AT follows autosomal recessive patterns of inheritance. Each time two AT carriers mate, there is a 25% risk of an affected child. In addition, every healthy sibling of an AT patient has a 66% risk of being a carrier. In some of the studies involving large number of families with AT, unusual features of inheritance such as low rate of consanguinity and lower than expected recurrence risks in the siblings have been observed [207].

A gene that causes AT was identified on chromosome 11q22–23 [208]. Two regions of the ATM gene include a region that is homologous to phopshoino- sitiol-3 kinase, a region that mediates cell growth signals. A second region homologous to RAD 3 and MEC 1 regulates cell cycle explaining diverse manifestations of AT [209]. It is now possible to identify disease causing mutations in patients with AT. In a large number of AT families from Scandinavia, who were screened for mutations using protein truncation test, fragment length, and heteroduplex analyses, the mutations could be detected in 82% of the cases [210].

7.6.9.6  Incidence

The incidence of AT is about three per million live births. The minimum frequency of AT gene in the US white population is estimated to be 0.0017 [211].