Atlas of Genetics and Cytogenetics in Oncology and Haematology

Nancy Uhrhammer1, Jacques-Olivier Bay1, Susan Perlman2, Richard A Gatti3 1. Centre Jean Perrin, Departement d'Oncologie Moleculaire, Clermont-Ferrand, France 2. UCLA School of Medicine, Dept of Neurology, Los Angeles, CA 90095 3. UCLA School of Medicine, Dept of Pathology, Los Angeles, CA 90095 April 2000; updated April 2002. Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder with early-onset cerebellar ataxia as its defining neurologic feature. It is the most common, recessively inherited, cerebellar ataxia in children under 5 years of age, with a prevalence of 1/40,000 to 1/100,000 live births [Swift 1985]. The accompanying extra-neural features aid in its clinical diagnosis and include conjunctival and cutaneous telangiectases, elevated levels of serum alphafetoprotein, chromosome aberrations, immunodeficiency with recurrent sinopulmonary infection, cancer susceptibility, and radiation hypersensitivity. Since identification of the causative gene, ATM (for Ataxia-Telangiectasia mutated), on chromosome 11q22-q23 [Gatti 1988, Savitsky 1995], the molecular basis of certain aspects of the disease have become clearer, though others remain to be elucidated [Gatti 1998, Meyn 1997, Shiloh 1996]. Note: see also cards on genes ATM, and NBS1 , and on cancer prone diseases Ataxia telangectasia and Nijmegen breakage syndrome CLINICAL FEATURES Neurologic Features Progressive cerebellar ataxia is almost always the presenting symptom and becomes apparent as early as the first year of life. Truncal and gait ataxia are slowly and steadily progressive, although between the ages of 2 and 5 years normal development of motor skills may temporarily mask this decline. This cerebellar degeneration typically leads to wheelchair dependence by the second decade. Migration abnormalities of prenatal Purkinje cell (PC) as well as post-natal PC degeneration have been seen [Vinters 1985], with thinning of the molecular and granule cell layers and minor changes in dentate and olivary nuclei and medullary tracts. Oculomotor abnormalities may also be seen. The typical patient with A-T is of normal intelligence, although the motor abnormalities make formal psychometric testing and standard learning programs difficult. Telangiectasia Telangiectases appear an average of two to four years after onset of the neurologic syndrome and are progressive. They are composed of dilated capillaries in the conjunctiva, and, later, on the ears, over the bridge of the nose, in the antecubital fossae, behind the knees, or more diffusely. They do not occur on internal organs nor are they generally associated with bleeding problems. Cancer Risk