Genetic over clinical diagnosis? Ataxia telangiectasia with heterozygous mutation

Ataxia telangiectasia (A-T) is a rare genetic form of early-onset autosomal recessive ataxia. It is due to mutations of the ATM gene, which is responsible of mending aberrant double-strand DNA breaks. Cerebellar atrophy with progressive ataxia, oculocutaneous telangiectasias, an increased risk of cancer (particularly lymphoid), radiosensitivity, immunodeficiency, recurrent sinopulmonary infections, and elevated serum levels of alpha-fetoprotein are the disease’s hallmarks.
Presentation of the case
A 24-year-old female, who began at age 2 with clinical data of ataxia, with gait incoordination. A neurology approach was initiated, finding cerebellar atrophy. At 5 years of age, telangiectasis became evident in scleras. She presented recurrent upper respiratory infections and oral candidiasis. Genetics found the fusion of genetic material corresponding to a chromosome 14 almost in the totality of its short arm with a chromosome 7 as a telomeric fusion, diagnosing ataxia telangiectasia. Elevation of alpha fetoprotein was reported. Progression of ataxia, with the need for wheelchair use at age 11. No alterations in immunophenotype, however, in periodic follow-up to rule out complications.
The discovery of a homozygous or compound heterozygous mutation in the ATM gene yields the conclusive diagnosis of A-T. Chromosomal translocation 7:14 is identified in about 5-15% of ataxia telangiectasia cases. Due to variations in genetic penetrance, not all features of the syndrome are present in patients with A-T, and the severity of each symptom also varies from person to person. There is no general consensus on the management of heterozygous carriers of pathogenic ATM mutations. The case in point did not present with immune alterations, however a thorough screening enables the prevention of recurring infections and early tumor identification, have a significant impact on these patients’ overall survival.

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