Extracts from the Lectures of the 32nd Nordic Congress of Dermato-Venereology, Tampere, Finland
quences for genetic counseling, particularly in families where
there is no previous history of a blistering disease.
Furthermore, identi?cation of mutations in the candidate
genes has formed basis for prenatal testing in families at risk
for recurrence, which can be performed by chorionic villus
sampling as early as the 10th week gestation. Recent work has
also focused on development of non-invasive prenatal testing
through analysis of the fetal DNA in the mother’s serum. Fetal
free DNA is readily detectable in mother’s blood by polymerase
chain reaction as early as the 5th week gestation, i.e., just at
the time when a woman may know that she is pregnant. Thus,
non-invasive prenatal diagnosis can provide information of
the fetal genotype to the parents and healthcare providers
earlier than currently available. The identi?cation of speci?c
mutations in families with EB has also formed the basis for
pre-implantation genetic diagnosis which is done even before
the pregnancy starts in the context of in vitro fertilization.
This approach has already been applied to a limited number
of cases with severe forms of EB.
Finally, identi?cation of speci?c mutations in the candidate
genes in different forms of EB has led to development of novel
molecular therapies of regenerative medicine, including gene
therapy and protein replacement approaches. Finally, allogeneic bone marrow transplantation for recessive dystrophic
EB has been demonstrated to alleviate blistering tendency in
a subset of patients. While the early results have warranted
cautious optimism, the long-term outcome of this process is
not yet known. Also, allogeneic bone marrow transplantation
carriers a signi?cant risk of complications and death, indicating that a careful analysis of the risk/bene?t ratio is in order.
Nevertheless, one could predict that treatment of single gene
disorders, such as EB, will be available soon.
JOUNI UITTO
pleomorphic ichthyosis (or non-LI/non-CIE). Included in the
latter subgroup of ARCI are 3 genetically distinct conditions:
(i) self-improving congenital ichthyosis due to ALOX12B/
ALOXE3 and TGM1 mutations; (ii) ichthyosis prematurity
syndrome due to SLC27A4 mutations, and (iii) bathing-suit
ichthyosis due to temperature sensitive TGM1 mutations,
explaining why lamellar ichthyosis appears only on skin
areas exposed to high ambient temperature, such as in utero
and under tight clothing in a hot climate. When diagnosing
ichthyosis in children and adults it is important not to miss
this subgroup of ARCI with mild skin symptoms, because
both medical advice (e.g., concerning anhidrosis and heatintolerance) and genetic councelling will differ compared to
other forms of more common ichthyosis. The most effective
therapy for ichthyosis remains retinoids together with emollients, but the side effects of retinoids are still a problem and
new, potent alternative remedies are needed.
A few other disorders of corni?cation were also discussed,
especially in the light of recent progress in our understanding
of their pathogenesis. Acral peeling skin syndrome (APSS) typically starts at the age of 3–6 months with super?cial blisters
on the toes and ?ngers. The aetiology is a de?ciency of TGM5,
encoding a transglutaminase essential for the adherence of
stratum corneum to stratum granulosum, especially when
acral skin is exposed to heat and friction. This recessive and
fairly common condition is genetically distinct from generalised peeling skin syndrome due to CDSN mutations. A rarer
type of recessive disorder of corni?cation is Mal de Maleda
due to SLURP-1 mutations; our recent investigations have
established that the Gamborg-Nielsen type of keratoderma,
typically found in northern Sweden, is a mild variant of Mal
de Maleda. The more common, dominant form of keratoderma, type Bothnia, on the other hand, is due to mutations
in an aquaporin gene, AQP5, which encodes a