128: Ataxia-Telangiectasia

Key Points

  • Disease summary:

    • Ataxia-telangiectasia (AT) is a recessive hereditary genomic instability disorder occurring in between 1 out of 40,000 and 1 out of 100,000 persons worldwide.

    • AT is clinically characterized by early-onset progressive cerebellar ataxia, telangiectasias of the skin and bulbar conjunctiva, progressive apraxia of eye movements, increased susceptibility to sinopulmonary infections, endocrine deficiencies and lymphoreticular malignancies, and other malignant tumors. Atypical forms including adult-onset AT and AT with early-onset dystonia including levodopa-responsive dystonia may occur.

    • Laboratory confirmation of the diagnosis is based on a combination of increased serum α-fetoprotein level, increased in vitro radiosensitivity, decreased or absent intracellular ATM protein levels on western blotting, and mutations in the ATM gene.

  • Hereditary basis:

    • AT is due to ATM gene mutations, which follow an autosomal recessive inheritance pattern. More than 600 mutations of the ATM gene have already been identified, most of which are unique to single families (private mutations). Genetic screening can be extensive and remains unsuccessful in 5% to 15% of cases.

  • Differential diagnosis:

    • AT variants have been recognized which include the Nijmegen breakage syndrome due to mutations in the NBS1 gene on chromosome 8q21, and AT-like disorder (ATLD) due to mutations in the MRE11.

    • Ataxia with ocular motor apraxia types 1 and 2 can clinically mimic AT. Other ataxia disorders including Friedreich ataxia and vitamin E-associated ataxia should also be considered.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria

At least one of the following

  • An increased serum α-fetoprotein level (not specific)

  • Increased in vitro radiosensitivity

  • Decreased or absent intracellular ATM protein levels on western blotting

  • Mutations in the ATM gene

Supportive Criteria

  • Reduced IgG or IgA levels (reduced in 80% and 60% of AT patients)

  • 7;14 chromosome translocation

Clinical Characteristics

AT should be considered in the context of progressive cerebellar dysfunction with onset in infancy. This can present as

Jun 2, 2016 | Posted by in HUMAN BIOLOGY & GENETICS | Comments Off on 128: Ataxia-Telangiectasia

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