Ataxia Telangiectasia (Louis-Bar syndrome)

1. Problem: Inability to repair damaged DNA (the AT mutated gene product is a signaling protein kinaseinvolved in cell-cycle control, DNA recombination, and other cellular responses to DNA damage)
2. Inheritance: auto recessive, chromosome 11q22-23

Triad:

1. Neuro/development
   • progressive ataxia, starting as toddler (2nd year of life, presenting symptom): Inability to ambulate independently by10 years of age. (Friedrich Ataxia: ataxia starts later, but before 10 yo)
   • MR
   • early development is usually normal, but walking might be delayed and when it occurs, a truncal ataxia is noted. This worsens and mean age of loss of walking is ten years.
   • dysarthria develops
   • Extrapyramidal signs such as athetosis and dystonia are often features.
   • Signs of a peripheral neuropathy may be evident from the second decade (Chediak-Higashi syndrome also presents with a peripheral neuropathy in the teens)
   • eye movements are jerky and oculomotor apraxia are common
2. telangiectasia of bulbar conjunctiva, ears, face
   • Ocular (3-7 years of age)
   • Cutaneous: on areas of trauma, sun exposure, flexor surfaces, malar
3. immune dysfunction (cellular immunity, thymic hypoplasia); recurrent sinopulmonary infections
   • humoral& cellular-apparent by 3-6 years of age
   • Abnormal number and function of T cells (hypoplasticthymus)
   • Variable immunoglobulin deficiency IgA(50-80%)
   • Recurrent sinopulmonaryinfections.

Other features

1. tendency to malignancies, esp lymphoreticular cancers (increased risk of cancer in heterozygotes, particularly breast cancer in women); lymphoma/leukemia; Increased sensitivity to ionizing radiation (even carriers)
2. may also have vitiligo, cafe-au-lait spots, premature graying of hair

Labs: Progressive lymphopenia involving both T and B cells. Decreased in vitroT-cell proliferation responses. Decreased IgAand IgE.

• Main causes of death: lymphoreticular cancer's and progressive neurologic disease
• Treatment: IVIG and antibiotics
• BMT is not a viable option because of cellular radiosensitivity.

See discussion of other diseases with dermatologic findings

CHLA board review course 2005
Baraitser and Winter, 1996. Color Atlas of Congenital Malformation Syndromes