The prevalence of epidermolysis bullosa in Scotland

H.M. HORN1,
G.C. PRIESTLEY1,
R.A.J. EADY2,
M.J. TIDMAN1
British Journal of Dermatology
Volume 136, Issue 4, pages 560564, April 1997

Summary
The prevalence of epidermolysis bullosa (EB) in Britain and most other countries is
unknown. Patients suffering from the inherited forms of EB and living in Scotland have been
traced. Two hundred and fifty-nine affected people from 76 families have been identified, of
whom 211 were clinically assessed. One-third of these Scottish EB sufferers had never been
seen by a dermatologist. In Lothian, where there appears to be a relatively high prevalence of
EB, 75% of patients were unknown to their general practitioners.
The point prevalence of all forms of EB at the outset of the study was 490 per million,
comprising EB simplex 286 per million and dystrophic EB 204 per million. Extrapolation of
accurate data available for the Lothians suggests that the point prevalence of all forms of EB
in Scotland is in excess of these figures.

Epidermolysis Bullosa

Author: M Peter Marinkovich, MD; Chief Editor: Dirk M Elston, MD

Epidemiology
Frequency

United States
Assuming that mild cases of epidermolysis bullosa simplex are reported only 10% of the
time, the affected population in the United States is approximately 12,500 persons. According
to a National Epidermolysis Bullosa Registry report,[5] 50 epidermolysis bullosa cases occur
per 1 million live births. Of these cases, approximately 92% are epidermolysis bullosa
simplex, 5% are dystrophic epidermolysis bullosa, 1% are junctional epidermolysis bullosa,
and 2% are unclassified. Patients with hemidesmosomal epidermolysis bullosa probably
constitute much less than 1% of total epidermolysis bullosa cases.

International
According to the National Epidermolysis Bullosa Registry,[5] the number of epidermolysis
bullosa cases in Norway is 54 cases per million live births, in Japan is 7.8 cases per million
live births, and in Croatia is 9.6 cases per million live births.

Mortality/Morbidity
Infancy is an especially difficult time for epidermolysis bullosa patients. Generalized
blistering caused by any subtype may be complicated by infection, sepsis, and death. Severe
forms of epidermolysis bullosa increase the mortality risk during infancy. Patients with the
Herlitz or letalis form of junctional epidermolysis bullosa have the highest risk during
infancy with an estimated mortality rate of 87% during the first year of life. In patients with
epidermolysis bullosa that survive childhood, the most common cause of death is metastatic
squamous cell carcinoma (SCC), as in the image below.

Recessively inherited dystrophic epidermolysis bullosa,

squamous cell carcinoma
This skin cancer occurs specifically in patients with recessively inherited epidermolysis
bullosa who most commonly are aged 15-35 years. In contrast, dominantly inherited
epidermolysis bullosa simplex and dystrophic epidermolysis bullosa and milder forms of
junctional epidermolysis bullosa may not affect a patient's life expectancy adversely.
One study reported that from 1979-2002, the overall age-adjusted annual mortality annual
mortality rate from bullous skin diseases 0.103 death per 100,000 population (2000 US
standard population).[6]

Age
Onset of epidermolysis bullosa is at birth or shortly after. The exception occurs in mild cases
of epidermolysis bullosa simplex, which may remain undetected until adulthood or
occasionally remain undiagnosed.

Letter to the Editor

Journal of Investigative Dermatology (2001) 116, 483484; doi:10.1046/j.15231747.2001.01279-11.x

Epidermolysis Bullosa Carrier Frequencies in the US Population

Ellen Pfendner, Jouni Uitto and Jo-David Fine*
1. Department of Dermatology and Cutaneous Biology and the DebRA Molecular
Diagnostics Laboratory, Thomas Jefferson University, Philadelphia, Pennsylvania,
U.S.A.
2. *Department of Dermatology and National Epidermolysis Registry, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.

Correspondence: Dr J. Uitto, Department of Dermatology and Cutaneous Biology and the

DebRA Molecular Diagnostics Laboratory, Thomas Jefferson University, Philadelphia, PA
19107, U.S.A.
Received 7 November 2000; Accepted 13 November 2000.
To the Editor:
Epidermolysis bullosa (EB) is a group of heritable blistering disorders in which three major
subtypes have been recognized on the basis of clinical, genetic, and ultrastructural features:
the simplex (EBS: OMIM 601001, 131800, 131900, 131950, 131760), junctional (JEB:
OMIM 226700, 226650, 226730), and dystrophic (DEB: OMIM 226600, 131705, 131850,
131750, 132000) forms (Fine et al. 2000). Our laboratory has been involved in the elucidation of the
genes and mutations causing two of the major subtypes, JEB and DEB, and has been
performing genetic analysis of patients and their families over the last several years (Pulkkinen &
Uitto, 1999
). During the course of these studies we are frequently consulted about families with an
affected child as to the recurrence risk and the type of genetic testing available. Frequently,
siblings and other family members become involved and are concerned about their carrier
status and their risk of having affected children. Through these inquiries, it has come to our
attention that there is no published estimate of the population carrier risk of each of the three
forms of EB. Recent information compiled by the National EB Registry (NEBR) (Fine et al. 1999)
estimates the incidence of each form of EB in the US population. From these data population
carrier frequencies can be calculated assuming HardyWeinberg equilibrium. The data in
Table 1 indicate the results of these calculations using the incidence data presented byFine et al.
(1999)
. Since both dominant and recessive forms of EBS and DEB are recognized, some caution
must be exercised in interpreting the data. Until mutation analysis has proven otherwise,
inheritance pattern is generally inferred from the pedigree. EBS, usually autosomal dominant,
may manifest with relatively mild phenotype, which is elucidated only upon close
examination and questioning of the patient and his/her family. Alternately, EBS may manifest
with a much more severe phenotype, which is usually identified in the neonatal period. In
addition, a few cases of recessively inherited EBS have been described (Chan et al. 1994;Rugg et al.
1994;Jonkman et al. 1996
), which may be more severe than most dominant cases, although the EBS
phenotype may not be a good predictor of inheritance pattern. Based on this information, the
majority of EBS cases may be considered to have a dominant inheritance pattern. Similarly,
dominant DEB is generally milder than the recessive forms of dystrophic EB, particularly the
Hallopeau-Siemens type; however, a number of cases in which mutations have been
identified by this laboratory (Christiano et al. 1996;Jrvikallio et al. 1997) and colleagues (Gardella et al. 1996;Tamai et al.
1999
) indicate that milder forms of recessive dystrophic EB are not uncommon, and these
cases, in the absence of family history, are clinically indistinguishable from mild, de novo
dominantly inherited DEB. On the other hand, dominant DEB cases are more numerous and
have been generally inferred from the pedigree, giving rise to the dominant and recessive
incidence values (Fine et al. 1999).

Table 1 - Carrier frequency of major EB subtypes in the US population.

Full table

The new mutation rate for any of the forms of EB has not been calculated; however, a
number of sporadic cases of DEB have been analyzed for mutations in the COL7A1 gene and
are presumed to result from germline mosaicism (Rouan et al. 1998;Hashimoto et al. 1999;Lee et al. 2000).
Continued elucidation of the mutations involved in all forms of EB will allow us to further
understand the relative numbers of new mutations, and to correlate type of mutation and
pattern of inheritance.
The carrier incidence information provided in Table 1 should enable genetics professionals to
accurately calculate the risk of recurrence to individual family members based on the family
history and provide up-to-date risk estimates that will facilitate accurate counselling of
extended families at risk.