what-when-how
In Depth Tutorials and Information
EDS classical type (types I and II) (OMIM
130000,130010) is usually caused by mutation occur-
ring in the genes encoding type V collagen, COL5A1
and COL5A2. 8,9 Phenotype is characterized by skin
hyperextensibility, fragile and soft skin, delayed wound
healing with formation of atrophic scars, easy bruis-
ing and generalized joint hypermobility. Patients can
also have muscle hypotonia and delayed gross motor
development. Complications of joint hypermobility
like dislocations/subluxations, manifestations of tissue
extensibility and fragility like hernias, and other derma-
tologic manifestations like molluscoid pseudotumors
and subcutaneous spheroids can be seen. 10
EDS, hypermobility type (type III) (OMIM 130020)
can be caused by mutation in the gene encoding tenas-
cin-XB (TNXB), but in most cases the causative gene
is unknown. 11 Phenotype is characterized mainly by
joint hypermobility. Skin is soft with normal or slightly
increased extensibility. Fragility or other significant
skin/soft tissue abnormalities are usually absent.
Other clinical features are recurrent joint dislocations
or subluxations, chronic joint pain, limb and/or back
pain. 12-15 Some of these patients may present with pre-
menopausal low bone mass with hypermobility.
There is some evidence that the BMD is reduced in
EDS, but the studies are few and the population size
small. Dolan et  al. reported on a group of 23 patients
with EDS (three patients with type I, seven patients
with type II and ten patients with type III) compared to
a matched control group. There were 17 women in each
group and the areal BMD at the spine and the femoral
neck and the ultrasound at the calcaneous were signifi-
cantly reduced in the EDS group. More importantly the
EDS group had a significantly increased fracture risk. 16
Carbone et  al. found that EDS type III patients had
lower femoral neck BMD compared to controls, but
when corrected for height, weight and activity the sig-
nificance disappeared ( p = 0.07), but the calcaneal BUA
(broadband ultrasound attenuation) remained signifi-
cantly reduced. 17
Classic EDS is caused by mutations in type V colla-
gen, which is structurally similar to type I collagen with
two alpha 1 chains and one alpha 2. It forms a hetero-
typic fibril with type I collagen and regulates the num-
ber and diameter of the collagen fibrils.18 18 There is a
paucity of information as to the extent of bone disease
with classic EDS, but we suspect on the basis of its func-
tion and the above preliminary data that it is likely to
be important in the differentiation of AOI.
Another rare disease with similarities to OI is arthro-
chalasia type EDS (type VII A and B) (OMIM 130060)
caused by mutations occurring in the genes encoding
type I collagen, COL1A1 and COL1A2, respectively;
generally caused by splice mutations skipping exon 6.
These mutations alter the protease cleavage site in the
alpha 1 or alpha 2 chains of type I collagen, resulting
in the inability of type I procollagen to be converted to
type I collagen. 19-22 Arthrochalasia type EDS (type VII
A and B) differs from AOI because of the marked joint
hyperflexibility with hip dislocations at birth, various
joint dislocations throughout life and muscle hypo-
tonia, but patients have blue sclera. 22,24-26 Byers et  al.
reported fractures in EDS type VII, consistent with
alterations in mineral deposition on collagen fibrils in
bony tissues. 22
In order to differentiate OI from EDS Table 28.1 may
be of some help. Blue sclera is not a good differentia-
tor of disease since it has been reported as present in
almost all types of EDS, particularly arthrochalasia and
dermatosparaxis types. 22-26 However, pre-senile hear-
ing loss occurs in around 50% of patients with AOI, 27,28
which is not reported with EDS.
ID IOPATHIC OSTEOPOROSI S
The differential diagnosis of adult OI type I includes
idiopathic osteoporosis. There are many similarities
between osteoporosis and OI including low bone min-
eral density and increased fractures. Paterson stud-
ied the natural history of OI 29 in men and women and
found that both had childhood fractures and the frac-
ture frequency declined with puberty, but increased
again at menopause. This implies that AOI bone
responds to estrogen similarly to osteoporotic or nor-
mal females.
There are two cases in the literature that were
thought to be instances of osteoporosis with type I col-
lagen abnormalities. Shapiro 30 reported on a 38-year-
old premenopausal woman with a cysteine-to-glycine
substitution at helix position 43 in the pro-alpha(I)
chain of type I collagen without fractures, but with
short stature, blue sclera, hypermobility and elastic
skin. The joint manifestations included shoulder dislo-
cations and multiple ankle sprains. She also sustained
a tear of her bladder and uterus during her last deliv-
ery. The BMD was more than two standard deviations
below normal at the spine and hip. Two of her four chil-
dren had joint laxity and no fractures. She was origi-
nally thought to have idiopathic osteoporosis, but this
case could be classified as either mild OI or ED disease.
Spotila 31 reported on a patient with a gly661ser
mutation in COL1A2 with features suggestive of post-
menopausal osteoporosis. She had a postmenopausal
vertebral fracture, but also had five previous fractures,
slightly blue sclera and mild hearing deficit. She had
childhood fractures, but these seemed to be related to
trauma. The BMD was very low. This case illustrates
that some cases of mild OI are difficult to differentiate
from postmenopausal osteoporosis.
 
Search WWH ::




Custom Search