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dominantly inherited forms of OI that result from muta-
tions in type I collagen genes are found in all population
studies and there is no reason to think that their incidence
would vary, as heterogeneity that might influence muta-
tion rate and type in the genes is small among population
groups. The contrast in frequency for recessive disorders
is striking among groups because, as a result of mutation
and probably population selection, some groups have a
relatively high frequency of specific mutations.
The measures of incidence and prevalence vary
among studies but the composite evidence from all is
that the incidence is probably just over 1/10,000 births
and the prevalence is a little less, which takes into
account the perinatal deaths of those with lethal forms
of OI. The measures of incidence suffer from the inabil-
ity to make the diagnosis of OI in infants with mild
forms of OI who have no evidence of fracture, bowing
or changes in scleral hue. This is compounded by the
increasing incidence of early pregnancy termination that
removes the severely affected pregnancies from the mea-
surements. In 1979, Sillence et al. reported an incidence
of 3.5/100,000 for OI type I in Victoria, Australia, and an
incidence in Australia of 1.6 per 100,000 for OI type II.
4
A study in Edinburgh revealed an incidence of OI of 1 in
20,000.
42
In a Northern Ireland survey spanning 12 years,
the incidence of OI type II was 1.5/100,000: only four
children were identified.43
43
Estimates based on the pres-
ence of fractures at birth range from 1.6/100,000 births
in Singapore
44
to 3.3/100,000 in France
45
to 15/100,000 in
the United Kingdom.
46
All these estimates are problem-
atic because of the small sample sizes used.
Barbosa-Buck et al. conducted a survey of osteochon-
dral dysplasias (OCD) based on more than 1.5 million
births in Latin America. OCD was identified in 492 new-
borns among 1,544,496 births (32/100,000) occurring and
examined in 132 hospitals of ECLAMC (Latin American
Collaborative Study of Congenital Malformations)
between 2000 and 2007. Among 211 cases from the best
documented group, 33% had OI, consistent with the idea
that OI is the most common of the inherited skeletal dys-
plasias and has an incidence that approaches 10/100,000.
Stevenson et al. surveyed the Utah Birth Defect Network
(United States) which collects population-based data on
births, still births and pregnancy terminations from all
Utah women for the prevalence of skeletal dysplasias,
from 1999 and 2008. In this group OI accounted for 40 (an
incidence of 7.9/100,000) and included all types of OI.
47
Prevalence figures are also difficult to obtain because
they require a complete survey of a representative set of
the entire population. These surveys are difficult to do in
the United States but Scandinavian countries include such
data in their health surveillance data, which include the
entire population. Perhaps the best study in this regard is
one of hearing loss in OI in the Finnish adult group. That
study estimated that the prevalence was about 8/100,000,
consistent with estimates of incidence and the expected
early loss of children with lethal forms of OI.
Given the current world population, these figures
would mean that the United States has 25,000-30,000
individuals with OI at any given time and about 400
newly affected people born each year. The frequency of
birth of infants with the severe forms of OI appears to
be decreasing as early pregnancy ultrasound becomes
standard and pregnancies with severe and lethal forms
of OI are terminated before 16-20 weeks' gestation. The
availability of prenatal diagnosis in families with severe
recessive disorders and in families in which a parent is
mosaic for a lethal form of dominant OI has changed
the epidemiology to some extent, although overall these
pregnancies probably represent about 15% of all preg-
nancies with OI.
In the United States, because of the marked heteroge-
neity of the population, recessively inherited forms of OI
have relatively little effect on either frequency or distribu-
tion among specific ethnic populations, with rare excep-
tions. For example, among African Americans, the carrier
frequency of a single LEPRE1 allele is about 1/240. As a
consequence about 1/240,000 births in the population
would be expected to be affected with a lethal form of OI
due to homozygosity for the mutation. This accounts for
about 15-20% of the infants with lethal OI born to this
group. In countries in which this mutation originated,
Ghana and Nigeria, some populations have a carrier fre-
quency that approaches 1/50. In that group the estimated
frequency at birth would be about 1/10,000 and so could
account for more than 75% of infants born with the peri-
natal lethal form of OI. When frequencies at these levels
are recognized, the nature of screening and testing will
change to better identify the high frequency forms of OI.
Any discussion of the epidemiology or prevalence
of OI must acknowledge uncertainty due to the recent
definition of new phenotypes as a consequence of the
discovery of genes associated with recessive OI types.
Recognition that there exist unrecognized possibilities
for mutations affecting collagen synthesis or that of other
bone-related proteins suggest that specific diagnoses will
eventually be possible for other osteopenic disorders cur-
rently undiagnosed. As new genes have been reported
the numbers of individuals affected by these mutations
have been expanded. Prior to the identification of these
genes, the affected individuals were either not consid-
ered to have OI or were diagnosed as OI with no type I
collagen mutation. An example of this was the definition
of OI type V in a group of patients previously considered
as Sillence type IV, a phenotype recognized earlier for its
clinical heterogeneity. The incidence of type VI OI, first
reported in 2002, is not established.
8
However, with the
identification of mutations affecting the chaperone pro-
tein SERPINF1, cases have now been identified in several
countries, including several French Canadian families,
18
