PEDBASE.org - The Pediatric Database - Detailed information of ATAXIA-TELANGIECTASIA

ATAXIA-TELANGIECTASIA

DEFINITION:

A chromosomal breakage disorder affecting multiple systems characterized primarily by ataxia, telangiectasia, and frequent sinopulmonary infections.

EPIDEMIOLOGY:

incidence: 1/40,000 live births
(most common of the degenerative ataxias)
age of onset:
- first 1-2 years (ataxia)
risk factors:
- familial - autosomal recessive
  - chrom. #: 11q22-q23
  - gene: ?
- M = F

PATHOGENESIS:

1. Background

considered to be a "chromosome breakage syndrome"
- one of at least 4 disorders associated with a high fre-quency of chromosomal breaks and rearrangements and with an increased risk of lymphoreticular (leukemia and lymphoma) and other malignancies
- other syndromes:
  - Bloom Syndrome
  - Fanconi Anemia
  - Xeroderma Pigmentosum

2. Genetic Defect

genetic defect -> defect in x-ray induced DNA repair mechanisms (but not UV-induced DNA repair mechanisms) -> may result in a differentiation defect -> failure of mesodermoentodermal interactions -> neurologic, cutaneous, and immune disorders

3. Chromosomal Abnormalities

chromosomal breaks, gaps, and rearrangements
- dicentrics and abnormal monocentrics
stable clones with chromosome 14 translocations

CLINICAL FEATURES:

1. Neurological Manifestations

1. Truncal Ataxia

initial symptom beginning in first 2 years of life
progressive with loss of ambulation by adolescence
chorea/choreoathetosis may develop before or instead of ataxia

2. Others

oculomotor apraxia (in 90% of cases)
- initially mild
- difficulty fixing smoothly on an object
- lateral overshooting of head followed by refixing eyes
horizontal nystagmus
muscle weakness and poor reflexes
initially normal intelligence but then regression to mildly retarded range (10 year level)
dull or expressionless face with excessive drooling

2. Cutaneous Manifestations

1. Telangiectasia

ocular & cutaneous telangiectasia develop from 2-10 years of age
first appear on bulbar conjunctivae (blood-shot eyes)
other areas affected: upper half of ears, flexor (exposed) surfaces of limbs (antecubital & popliteal fossae), butterfly distribution on face, hard palate
exacerbated by sunlight, irritation, or friction
become more prominent and more extensive with time

2. Others

atopic dermatitis, cafe-au-lait spots, cutaneous atrophy, hypo- & hyperpigmentation, loss of skin elasticity, nummular eczema, premature greying of hair

3. Other Manifestations

1. Immune

recurrent sinopulmonary infections
- may lead to bronchiectasis

2. Endocrine

growth failure
lack of development of secondary sex characteristics due to ovarian hypoplasia

3. Neoplasms

1. Lymphoreticular Tumors

lymphoma - Hodgkin's Disease, Non-Hodgkin's Disease
lymphocytic leukemia

2. Others

brain tumors
hepatocellular carcinoma
gonadoblastomas and dysgerminomas in some females
50 to 100-fold greater chance of developing a neoplasm
death due to infection or neoplastic disease
- 67% die by age 20

INVESTIGATIONS:

1. Serum

deficiency of IgA, IgE or both
- 50-70% - deficiency of both
- 20-40% - deficiency of IgE only
elevated alpha-fetoprotein and carcinoembryonic antigen (CEA)
karyotype: high incidence of chromosomal breaks especially chromosome 14
elevated FSH and LH with reduced estrogen

MANAGEMENT:

1. Supportive

no treatment available
surveillance for and treatment of all infections and neoplasms
minimization of radiation (x-rays or cancer treatment) as may induce chromosomal damage -> neoplasm

INTERNET LINKS:

The A-T Children's Project Home Page

Pediatric Database - ATAXIA-TELANGIECTASIA

Pediatric Organization - Pedbase [at] Gmail.com