Xeroderma Pigmentosum (XP)

A syndrome characterized by a defect in ultraviolet radiation-induced DNA repair mechanisms and by a severe sensitivity to all sources of ultraviolet radiation (especially sunlight). XP is categorized into seven complementation groups according to the capacity of the body to repair DNA. Life-threatening. The DNA damage is cumulative and irreversible. Sometimes lethal in infancy or childhood.

Xerodermic Idiocy; Kaposi Disease.

A group of rare autosomal recessive inherited disorders that were first described by Ferdinand Ritter von Hebra, Austrian dermatologist, and Moritz Kohn Kaposi, Hungarian dermatologist, in 1874.

1:250,000 in general population; higher in Japan (1:40,000). Sex ratio is about 1.

A rare autosomal recessive genetic defect.

Caused by a defect in nucleotide excision repair (NER), leading to an inability to repair DNA damaged by ultraviolet radiation. There are two types of NER: global genome (GG-NER) and transcription coupled (TC-NER). There are seven XP repair genes (XPA to XPG), with seven principal complementation groups of XP corresponding to defects (four other subcategories have been described). Frequency and severity varies among forms; XPA and XPC are the most common.

Clinically evocated by the skin lesions with a three-stage evolution. Skin is normal at birth. After the age of 6 months, a diffuse erythema, scaling, and freckle-like areas of increased pigmentation, initially on the face can be seen. The second stage is characterized by poikiloderma and the third stage by the appearance of numerous malignancies. Diagnosis may be suspected and can be made during the first stage. It is confirmed in vitro and by a skin biopsy.

Normally, it involves the skin (photosensitivity, skin hypoplasia, increased patchy skin pigmentation, decreased or increased irregular skin pigmentation, hyperkeratosis, hemangioma capillary, telangiectasia skin, neoplasia), eyes (photophobia, optic disc atrophy, conjunctival telangiectasia, paresis of ocular muscles), and CNS (more common in XPA and XPD: e.g., abnormality, seizures, areflexia, cerebral cortex atrophy, microcephaly, deafness, and mental retardation). Other possible features include ectopic testes and teeth anomalies.

Evaluate the neurological function (clinical, electroencephalogram, CT) and ocular lesions. Avoid radiographs because of photosensitivity.

Patient behavior in the operating room may be affected by photophobia. It is recommended to dim the light. As with other dermatological illness, intraoperative padding (pressure points) and positioning is very important. Difficult airway management is possible because of skin atrophy, scarring and macroglossia.

The use of inhalational agents is questioned because of their potential interaction with the NER in cells of patients affected with XP, worsening the symptoms of the disease. The interaction between anesthetic drugs and antiepileptic treatment must be considered. Special attention must be given to the administration of new medications and their photosensitivity properties (e.g., antibiotics) medications that might affect DNA must be avoided.

De Santis Caccione Syndrome: This particular syndrome is usually present in xeroderma pigmentosum group A, and shows, in addition to XP, severe mental deficiency, choreoathetoid neurologic signs (usually), dwarfism, and gonadal hypoplasia.

Netherton Syndrome: Congenital disorder characterized by abnormal brittle hair (diagnostic sign). Other features include onychodystrophy, cataracts, and teeth problems. Associated with mental retardation, skin sensitivity to light, and skin ichthyosis.

Bloom Syndrome: Cancer-prone genetic disorder inherited as autosomal recessive disease. Patients present with small and short stature, erythematous skin, butterfly facial rash sensitive to sunlight, excessive hypoand hyperpigmented lesions, and a high rate of bacterial infection as a result of immunodeficiency (requiring antibiotics during surgery). Other features include chronic lung disease and diabetes. Common among Ashkenazi Jews.

Cockayne Syndrome: The characteristics of this autosomal recessive inherited disease are dwarfism, precociously senile appearance, pigmentary retinal degeneration, optic atrophy, progressive sensorineural deafness, sensitivity to sunlight, and mental retardation. Disproportionately long limbs with large hands and feet and flexion contractures of joints are usual skeletal features.

Fanconi Anemia: Spontaneous chromosomal aberrations associated with hypocellular marrow, pancytopenia, and constitutional aplastic anemia, presenting in the first years of life, and associated with growth retardation.