The majority of patients present with truncal ataxia by the age of 2 years and almost all are affected by the age of 6 years. The disease is progressive with poor prognosis [212]. About one-third of cases have died by the age of 15 years and survival beyond the age of 30 years is very unusual [213].

AT patients are likely to have recurrent sinopulmonary infections because of immune dysfunction for which they need appropriate long-term care. The AT-associated malignancies such as lymphoma and leukemia require modified chemotherapy and radiotherapy dosages because of hypersensitivity to radiation and chemotherapy-induced DNA damage [216].

7.6.9.8  Signs and Symptoms

The clinical manifestations of AT involve many organs with predominance of neural, ocular, and cutaneous changes. Progressive cerebellar ataxia in early childhood is the hallmark of AT and is seen in all cases [214]. Other neurologic findings include cho- rea-athetosis, dysarthria, drooling, and hypotonic facies. The telangiectasia involves the bulbar conjunctiva and the skin of the arms, neck, and shoulder region. The telangiectasia have later onset, usually by the age of 6 years, and may even be absent in some cases. Ocular motility disorder in AT is characterized by oculomotor apraxia of the vertical gaze [212]. Presence of oculomotor apraxia with cerebellar ocular motor abnormalities is highly suggestive of AT [215].

Other significant manifestations of AT are dysplasia of the thymus gland, recurrent pulmonary infections, susceptibility to neoplasia, endocrine abnormalities, and progeric changes [216]. Lymphoma and leukemia occur in early adulthood in about 15% of cases representing 1,000 times greater incidence than the general population. The leukemia is exclusively lymphocytic in origin. The lymphoid malignancies arise from both B- and T-cells [217].

7.6.9.9  Diagnosis and Diagnostic Aids

The diagnosis of AT is essentially based on clinical findings. The laboratory markers include elevated serum alpha-fetoprotein after 2 years of age, elevated plasma carcinoembryonic antigen, and low serum antibody levels (IgA, IgG2, and IgE). In vitro studies on lymphocytes show spontaneous chromosome breaks and rearrangements and cultured fibroblasts show increased sensitivity to ionizing radiation.

7.6.9.11  Social and Family Impact

It has been suggested that AT heterozygotes, such as asymptomatic parents, have a risk of cancer involving the breast, pancreases, stomach, bladder, and ovary [218]. The estimated relative risk of breast cancer is 6.8, representing about 9% of all breast cancer in the United States [219]. These findings are not usually accepted with others not finding any enhanced risk of breast cancer in AT heterozygotes [220].

7.7  Retinal Caverous Hemangioma

7.7.1  Introduction

Retinal cavernous hemangioma is a rare congenital vascular hamartoma with clusters of saccular aneurysms filled with dark blood, giving a “cluster-of- grapes” appearance [221]. Occasionally, it is associated with cerebral cavernous malformations as an autosomal dominant syndrome with high penetrance and variable expressivity [222, 223]. Retinal and cerebral cavernous malformation syndromes have been proposed to be included as a part of neuro-oculo-cutane- ous disorders, but the association with cutaneous hemangiomas is inconsistent [221].

7.7.2  Historical Context

Scheyhing described a retinal vascular tumor composed of multiple dilated vessels with the appearance of grapes in 1937 [224]. In 1971, Gass proposed the term “cavernous hemangioma” and stressed its