High incidence of Xeroderma Pigmentosum in a countryside community in the state of Goiás, Brazil

Received on: 08/03/2011
Approved on: 15/03/2011

This study was performed at the Hospital
Geral de Goiânia - Dermatology Department
(an institution of the Goiás State Department
of Health) – Goiânia (GO), Brazil.

Conflicts of interest: none
Financial support: Federal Health System and
Goiás State Department of Health

Abstract

We describe a settlement in the Araras District in central Brazil that presents a high incidence of Xeroderma Pigmentosum.Twenty patients have had clinical diagnoses compatible with this condition so far. Reports from surviving relatives suggest an additional 20 deaths linked to typical Xeroderma Pigmentosum symptoms.This is possibly the first report of its kind in the literature, due to the extension of the family factor prevalence, the patients’ age range and different characteristics of the clinical manifestations.

Keywords: XERODERMA PIGMENTOSUM, SKIN NEOPLASMS, GENETICS, EPIDEMIOLOGY

COMMUNICATION

Xeroderma Pigmentosum (XP) is rare recessive autosomal inherited condition characterized by a high sensitivity to sunlight.The early appearance of skin tumors – with a frequency 1,000 times higher than average, which causes a significant reduction in life expectancy – is one of its main clinical characteristics. XP patients also present diverse clinical manifestations – such as neurological complications, redness of the eyes, hearing loss, development abnormalities and early aging in some organs (such as the skin). 1

The molecular cause of XP was identified when it was demonstrated that patients’ cells presented reduced levels of repaired DNA synthesis;2 their skin cells are highly sensitive to ultraviolet (UV) light and present high mutagenicity levels after irradiation. Thus there is a strong correlation between cellular phenotype and genetic instability, which must cause skin tumors to develop in XP patients. In most XP patients, such cellular phenotypes are caused by the cells’ incapacity to remove DNA UV-induced lesions, due to genetic flaws in the DNA repair mechanism known as nucleotide excision repair. Some patients have a normal repair mechanism, yet have problems in the replication of damaged DNA; such cases are known as XP variants.

From a genotypic point of view, XP clinical manifestations are accompanied by an equally polymorphic variation. Seven groups, classified as XPA to XPG, represent individual repair genes; the XP variant type is known as XPV.3,4 While less severe – with a better prognosis and longer life expectancy – XPV presents similar clinical characteristics to other XP types.

In spite of the syndrome’s high genetic diversity, the Araras case suggests that XPV is characterized by a defect in the post-replication repair of DNA.The mutated gene is identified by a culture of the patients’ cells, which confirms a clinical diagnosis of the condition. A 5-year-old red-haired male child was examined in 2007, presenting with ephelides in the face. The patient returned in 2009 for a consultation, and was diagnosed with probable XP. In a 2010 field visit to Araras, a city of about 1,000 where the child and his family live, 20 new cases compatible with XP were identified. According to residents’ reports, more than 30 other individuals have died with symptoms typical of the disorder in the last few decades.

In addition to the patients identified in Araras, there are reports of individuals with typical XP symptoms in neighboring cities.The literature describes a second group with XP: approximately 10 Indians from Guatemala with serious symptoms who died before 10 years of age.5 The study of the Araras group will certainly bring many advances in the understanding of the disorder, due to the extension of the prevalence in the patient’s extended family, the patients’ age range, and different characteristics of clinical manifestation (Figures 1-5).

Although it is rare for XP patients to reach an advanced age, some in the Araras group (age range 8-76) are elderly, with serious lesions (Table 1). Most patients are of Caucasian origin, however three were identified as having black ancestors. Despite the high frequency of individuals with XP clinical symptoms, it was only recently that the characteristics described by the term “xeroderma” were recognized among them. The initial care consists of the removal of tumors.The dermatologic follow-up must include periodic control, protection against the sun and other elements. and treatment of premalignant and malignant lesions. Medical care must also include multidisciplinary specialists: genetic, ophthalmologic, neurological, oncologic, psychological and social assistance.

References

1 . Historical aspects of xeroderma pigmentosum and nucleotide excision repair. Adv Exp Med Biol. 2008;637:1-9.

2 . Defective repair replication of DNA in xeroderma pigmentosum. Nature. 1968; 218(5142): 652-6.

3 . Chigancas S,Galhardo RH.Carvalho,Menck CF The eukaryotic nucleotide excision repair pathway. Biochimie. 2003;85(11):1083-99.

4 . Exploring DNA damage responses in human cells with recombinant adenoviral vectors." Hum Exp Toxicol. 2007;26(11):899-906.

5 . Xeroderma pigmentosum group C in an isolated region of Guatemala. J Invest Dermatol. 2007;127(2):493-6.