What is Ataxia-telangiectasia?

Ataxia-telangiectasia, also known as Louis-Bar syndrome, is a rare inherited multisystem disorder distinguished by: ataxia, oculocutaneous telangiectasia, immunodeficiency, and cancer susceptibility, as well as radiation toxicity.

Causes of Ataxia-telangiectasia

Ataxia-telangiectasia is an autosomal recessive disorder in which one ataxia-telangiectasia gene is inherited from each parent. ATM gene inactivation mutations are found on chromosome 11q22-23. In Purkinje cells of the cerebellum, as well as in brain, skin, and conjunctival endothelial cells, the ATM gene codes a protein kinase that is important for double-strand-break DNA repair.

Clinical features of Ataxia-telangiectasia

Children with ataxia-telangiectasia appear normal at birth, and symptoms do not show until they learn to walk at age one or two.

Neurological manifestations:

Unsteady walk
Abnormal jerky movements
Poor coordination of the limb
Slow and slurred speech
Facial features: dull, sad, inattentive
Growth is delayed
One-third of patients experience learning difficulties

Oculocutaneous manifestations:

Telangiectases are the second most common clinical manifestation of ataxia-telangiectasia. Dilated conjunctivae vessels appeared first at the angles of both eyes and spread horizontally in the equatorial region of the conjunctivae toward the corneal limb. They may have a subtle effect on the internal ears, eyelids, and cubital and popliteal fossas. Telangiectasia patches in other areas of the skin are less common.

Some gray hairs are usually noticed, even in young children. During adolescence, the facial skin becomes atrophic and sclerodermoid, with atrophic areas resembling large varicella scars. Pigmentary changes occur in a mottled pattern of hypopigmentation and hyperpigmentation.

Additional skin changes may include:

Café au lait spots
Vitiligo
Cutaneous granulomas: red-brown nodules and infiltrating ulcerative plaques are frequently seen on the face and limbs.
Seborrheic dermatitis, keratosis pilaris, common warts, and hirsutism of the arms and the legs are also frequently found.
Multiple senile keratoses and basal cell carcinomas of the face have been reported in patients in their 20s.

Patients with ataxia-telangiectasia have a compromised immune system, making them susceptible to recurring sinus and bronchial infections. Also, they are at a greater risk of developing malignancies.

Diagnosis of Ataxia-telangiectasia

The clinical suspicion of ataxia telangiectasia is supported by:

Elevated serum levels of alpha-fetoprotein (AFP)
A cytogenetic study may help confirm the diagnosis (7;14 translocations).
The molecular diagnosis.

If a parent has an inactivating ATM gene mutation, a prenatal diagnosis can be made.

Treatment of Ataxia-telangiectasia

There is no cure for ataxia-telangiectasia. The management of ataxia-telangiectasia focuses on treating symptoms, preventing complications, and, most importantly, supporting patients and their families. This could involve physiotherapy, speech therapy, and antibiotics for infection. Death usually occurs in early or middle adolescence, mainly from bronchopulmonary infection, less frequently from cancer, or a combination of both.

Written by:

Atheer Alhuthaili , Medical Student.

Revised by:

Naif Alshehri, Medical Intern.

Article References:

DermNet.

Uptodate.

Amboss

Picture Reference:

Bolognia 4th edition.