Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting
in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers.
It is a rare genetic autosomal recessive disorder and has been found in all continents and
racial groups. Estimated incidences vary from 1 in 20, 000 in Japan to 1 in 250, 000
in the USA, and approximately 2.3 per million live births in Western Europe.
The first features are either extreme sensitivity to sunlight, triggering severe sunburn,
or, in patients who do not show this sun-sensitivity, abnormal lentiginosis (freckle-like
pigmentation due to increased numbers of melanocytes) on sun-exposed areas.
This is
followed by areas of increased or decreased pigmentation, skin aging and multiple
skin cancers, if the individuals are not protected from sunlight. A minority of patients
show progressive neurological abnormalities.
There are eight XP complementation groups,
corresponding to eight genes, which, if defective, can result in XP. The products
of these genes are involved in the repair of ultraviolet (UV)-induced damage in DNA.
Seven of the gene products (XPA through G) are required to remove UV damage from the
DNA. The eighth (XPV or DNA polymerase η) is required to replicate DNA containing
unrepaired damage. There is wide variability in clinical features both between and
within XP groups.
Diagnosis is made clinically by the presence, from birth, of an
acute and prolonged sunburn response at all exposed sites, unusually early lentiginosis
in sun-exposed areas or onset of skin cancers at a young age. The clinical diagnosis
is confirmed by cellular tests for defective DNA repair. These features distinguish
XP from other photodermatoses such as solar urticaria and polymorphic light eruption,
Cockayne Syndrome (no pigmentation changes, different repair defect) and other lentiginoses
such as Peutz-Jeghers syndrome, Leopard syndrome and Carney complex (pigmentation
not sun-associated), which are inherited in an autosomal dominant fashion.
Antenatal
diagnosis can be performed by measuring DNA repair or by mutation analysis in CVS
cells or in amniocytes.
Although there is no cure for XP, the skin effects can be
minimised by rigorous protection from sunlight and early removal of pre-cancerous
lesions. In the absence of neurological problems and with lifetime protection against
sunlight, the prognosis is good. In patients with neurological problems, these are
progressive, leading to disabilities and a shortened lifespan.
Source: Alan R Lehmann, David McGibbon and Miria Stefanini. Orphanet Journal of Rare Diseases