Osteogenisis Imperfecta (Oi)- Essay, Research Paper
Osteogenisis Imperfecta (OI)-
Osteogenisis imperfecta (OI) is a rare genetic
disorder of collagen synthesis associated with broad
spectrum of musculoskeletal problems, most notably bowing
and fractures of the extremities, muscle weakness,
ligamentous laxity, and spinal deformities.
(Binder, 386). Other collagen-containing extraskeletal
tissues, such as the sclerae, the teeth, and the heart
valves are also affected to a variable degree. OI has a
common feature of bony fragility associated with defective
formation of collagen by osteoblasts and fibroblasts.
(Smith, 1983, 13) This disease, involving defective
development of the connective tissues, is usually the result
of the autosomal dominant gene, but can also be the result
of the autosomal recessive gene. Spontaneous mutations are
common and the clinical presentation of the disease remains
to be quite broad. (Binder, 386)
OI is most commonly referred to as brittle bones ,
but other names include: fragilitas ossium, hypolasia of
the mesenchyme, and osteopsathyrosis. Osteogenisis
imperfecta is still not completely understood, and while
there have been advances in diagnosing the disease,
treatment is still limited.
Osteogenisis imperfecta is the result of mutations
in the genes for type I collagen.
In the mild dominantly inherited form of OI (type I), a
non-functional allele for the alpha 1 (I) chain halves
collagen synthesis, (Smith, 1995, 169) and is largely
responsible for the inheritance. Single base mutations in
the codon for glycine causes lethal (type II) OI by wrecking
the formation of the collagen triple helix. Types III and
IV are the less dram- atic outcomes of similar glycine
mutations in either the alpha 1 (I) or the alpha 2(I)
chains.(Smith, 1995, 169)
The clinical signs can be caused from defective
osteoblastic activity and defective mesenchymal collagen
(embryonic connective tissue) and its derivatives, such as
sclera, bones, and ligaments. The reticulum fails to
differentiate into mature collagen or the collagen develops
abnormally. This causes immature and coarse bone formation
and thinning. (Loeb, 755)
SIGNS AND SYMPTOMS
The signs and symptoms of OI vary greatly depending
on the type. The most commonly used classification is the
Sillence (type I to IV):
Type I is the mildest form of OI and is inherited as
an autosomal dominant trait. The sclerae(middle coat of
eyeball) is distinctly blue. Type I is broken down into IA
and IB — the difference being whether dentinogenesis is
present. IA has a life expectancy nearly the same as the
general public. The physical activity is limited, and may
appear to have no disability at all. The bones have a
mottled or wormian appearance, forming small islands.
Type II is lethal in utero or shortly there
afterbirth. The survivors live from just a few hours to
several months. The kayotypes of parents are usually normal.
This type is broken down into three subgroups: IIA is
characterized by a broad, crumpled femora and continuos rib
beading, IIB by minimal to no rib fractures, and IIC by a
thin femora and ribs with extensive fracturing. While in
the uterus, there is poor fetal movement, low fetal weight,
poor ossification of the fetal skeleton, hypoplastic lungs,
the long bones of the upper and lower limbs are shortened or
deformed, and the head is soft. Intrauterine fractures
occur, and parinatal death is usually from intracranial
hemorrhage due to vessel fragility or respiratory distress
from pulmonary hypoplasia. The bones and other tissues are
extremely fragile, and massive injuries occur in utero or
delivery. The ribs appear beaded or broken and the long
bones crumpled. (Isselbacher, 2111)
Type III and IV are intermediate in severity between
types I and II. Type III differs from I in its greater
severity, and from IV in that it increases in severity with
age. It can be inherited as either a autosomal recessive or
dominant trait. The sclerae is only slightly bluish in
infancy and white in adulthood, although the average life
expectancy is 25 years. Type IV is always dominant. With
types III and IV multiple fractures from minor physical
stress occurs leading to progressive and severe deformities.
Kyphoscoliosis may cause respiratory impairment and
predisposition to pulmonary infections. Popcorn-like
deposits of mineral appear on the ends of long bones.
The symptoms of OI tarde (types I, III and IV) can
appear when the child begins to walk, and lessens with age.
The tendency to fracture decreases and often disappears
after puberty. Later in life, particularly during pregnancy
and after menopause, more fractures occur. The bones are
usually slender with short, thin cortices and trabeculae
(fibers of framework), but can also be unusually thin.
(Smith, 1983, 136) Narrow diaphysis of the long bones
contributes to the fractures and bowing deformities.
Scoliosis is common. The haversian cells are poorly
developed. The bones lack minerals needed to form bone
matrix. Epiphyseal fractures (end of the bone) results in
deformities and stunted growth (dwarfism). Osteopenia, the
decrease in bone mass, is symptomatic.
Other signs of OI include hyperextensibility of the
joints — double-jointedness– and abnormally thin,
translucent skin. Discolored (blue-gray or yellow-brown) and
malformed teeth which break easily and are cavity prone are
found in patients Patients with OI have a triangular-shaped
head and face, a bilaterally bulging skull, and prominent
eyes with a wide distance between the temporal region.
Hearing loss by the age of 30-40 is the result of
the pressure on the auditory nerve because of the deformity
of its canal in the skull, and the development of
otosclerosis. Recurrent epistaxis (nosebleeds), bruising
and edema (especially at the sight of fractures), difficulty
tolerating high temperatures and mild hyperpyrexia are other
symptoms. Thoracic deformities may impair chest expansion
and the ability to effectively breath deeply and cough.
(Loeb, 755) Patients are also more susceptible to infection.
In assessing a patient data is needed about the
genetic history and birth of the child, as well as a
complete development assessment from birth. Vital signs are
taken, and periods of increased heart and respiratory rate
and elevated body temperature are note-
worthy. Skin should be examined for color, elasticity,
translucency, and signs of edema and bruising. A
description of position and appearance of a child s trunk
and extremities and facial characteristics should be noted.
The height of the child in terms of expected growth, signs
of scoliosis or laxity of ligaments, and range of motion of
the joints are all important. Sight and hearing should be
tested since there are sensory problems associated with OI.
The appearance of the sclerae and tympanic membranes and
defects of primary teeth and gums are important. (Jackson,
X-rays usually reveal a decrease in bone
density. There is no consensus, however, as to whether the
diagnosis can be made by microscopy of bone specimens.
(Isselbacher, 2112) DNA sequencing and incubating skin
fiboblasts are two ways help diagnose OI.
Prenatal ultrasonography is used to detect severely
affected fetuses at about 16 weeks of pregnancy. Diagnosis
of the lethal type II by ultrasound during the second
trimester of pregnancy is by the identification of fractures
of the long bones. Compression of the fetal head is seen by
ultrasound probe, and low echogeneity of the cranium can be
signs of skeletal dysplasia (faulty development of the
tissues). Diagnosis is confirmed by postmortem examination
including radiography and biochemical studies of cultivated
fibroblasts from the fetus. (Berge, 321) Diagnosis by
analyzing DNA sequencing can be carried out in chronic villa
biopsies at 8-12 weeks.
There is no known treatment of OI at this time.
Treatment therefore is predominantly supportive and
educational. Because of multiple fractures and bruising, it
is important to diagnose this disease in order to prevent
accusations of child abuse.
Treatment of fractures is often challenging because
of abnormal bone structure and laxity of the ligaments.
Splinting devices are used to stabilize the bones and to
protect against additional fractures. Treatment aims to
prevent deformities through use of traction and/or
immobilization in order to aid in normal development and
rehabilitation. Limb deformities and repeated fractures can
be corrected by intramedullary rods — telescoping
rods that elongate with growth. After surgical placement of
the rods, extensive post- operative care is required because
greater amounts of blood and fluid are lost. (Loeb, 755) It
should be noted that the healing of fractures appear to be
normal. (Isselbacher, 2112) Braces, immobilizing devices and
wheelchairs are necessary.
Physical therapy is important in the treatment of
OI. Bone fracture density in unfractured bone is decreased
when compared with age-matched controls due to limited
exercise, so it is essential to stay as active as possible.
Physical therapy is also used for strengthening muscle and
preventing disuse fractures with exercises with light
resistance, such as swimming.
Regular dental visits are necessary to monitor the
teeth. Monitoring by opthalmol-
ogists for vision and audiologits for hearing is also
essential. Radiologists need to examine the structure and
density of the bones, and an orthopedist is needed to set
fractures and take care of other bone related problems.
Counseling and emotional support is needed for both
the patient and the family. It is important not to limit a
child because of his/her disabilities, and to realize that
many victims of this disease live successful lives. Debrah
Morris, a successful business woman, and active fighter for
disability rights and helping other patients of OI, says,
If I had the choice to be anyone in the world, I would be
exactly who I am. The people I have met, the challenges I
have faced, the opportunities that I have been presented —
all are directly related to dealing with being a little
person with brittle bones. (Kasper, 53) Many of the
symptoms of OI can be confused with those of a battered
child. X-rays are used to show evidence of old fractures
and bone deformities to distinguish the difference. The
Osteogenesis Imperfecta Foundation (OIF) has is a national
support group that offers assistance to families in this
position and to increase public awareness. The OIF has a
medical advisory council, chapters, support groups, regional
meetings, biennial national conferences, and parent contacts
to help families feeling alone and helpless. They also
publish a newsletter, provide literature and videos about
OI, and sponsors a fund to support research.
Magnesium oxide can be administered to decrease the
fracture rate, as well as hyperpyrexia and constipation
associated with this condition. (Anderson, 1127) A
high-protein, high-carbohydrate, high-vitamin diet is needed
to promote healing. A growth hormone has also been
administered during childhood, and is shown to substantially
increase growth. Treatment with bisphosphorates and related
agents has been discussed to decrease bone loss, but no
controlled studies have been done. (Isselbacher, 2113)
Since there is no cure for oseogenesis imperfecta,
appropriate and properly timed rehabilitation intervention
is of the utmost importance to ensure that the child is able
to function to the best of his/her ability in society. A
ten year study that was submitted in 1992 proves this.
25 of 115 children with severe OI were observed
since birth or infancy at the National Institutes of Health,
MD and the Skeletal Dysplasia Clinic at the Children s
National Medical Center in D.C. One was Type I, two Type
II, nine Type III, and thirteen Type IV. They were
classified by physical characteristics and functional
Group A consisted of those who were severely dwarfed
with large heads and marked bowing , contractures, and
weakness of extremities. The highest functional skill
expected was independent sitting. Group B was growth
deficient, but with a normal sized head. Femoral bowing,
scoliosis, and contractures of the hip flexors were
characteristics. they were expected to stand and/or
ambulate with braces. Group C were less growth deficient,
and had good strength, but poor endurance. They had marked
joint laxity and poorly aligned lower extremity joints, but
were ambulators. (Binder, 386-387)
Group A patients were the most severely involved.
Most were basically sitters. The majority were totally
dependent in their self care. Group B had the potential to
become at least short-distance ambulators. These patients
had acquired the ability to move to sitting, but had
transitional moving problems, such as sitting to standing.
All were part-
ially independent in their self care. Group C had
antigravity strength and 50% had good strength in their
extremities. All were physically active and
age-appropriately independent, but none were good
long-distance walkers. (Binder, 387-388)
Progressive rehabilitation of these groups all
included posture exercises and active range of motion and
strengthing exercises. Group B had additional ROM and
posture exercises, as well as Developmental exercises.
Group C added coordination activities.
Conclusion, Management of patients with OI should
address the child s functional needs. Even though the
degree of disability may be severe, management should not be
limited to orthopedic procedures and bracing. Treatment
planning should be considered, but not totally based on
genetic, anatomical, and biochemical abnormalities. Our
ence suggests that clinical grouping based in part on
functional potential can be useful in the appropriate
management of children with OI. (Binder, 390) Independence
was stressed in this study, and even patients with limited
sitting ability, upper extremity function can be improved to
at least minimal independence in self-help skills.
Potential ambulators should be helped because, although
their ability might not progress past indoor ambulation,
walking will make them more independent and may result in
increased bone mineralization. Poor joint alignment, poor
balance, and low endurance can all be improved with
persistent, individualized physical and occupational
therapy. For best results, therapy should be started as
soon after birth as possible. Mainstreaming school aged
children is also important. All of this together leads to
age-appropriate social development and markedly improved
independence and quality of life in the majority of
patients. (Binder, 390)
Osteogenesis imperfecta is the most common genetic
disorder of the bone. It occurs in about 1 in 20,000 live
births, and is equally prevalent in all races and both
sexes. The Type I OI has a population frequency of about 1
in 30,000. Type II has a birth incidence of about 1 in
60,000. Types III and IV are less common and may be as
high as 1 in 20,000. (Isselbacher, 2111) The occurrence of
OI in families with no history or blue sclerae is about 1 in
3,000,000 births.(Smith, 1995, 171) The recurrence risks in
families is estimated to be 6 to 10%, but is only estimated
because most couples choose not to have any more children.
15 to 20% of patients with OI do not carry the gene for
abnormal collagen, making many wonder if there is yet
another genetic problem undiagnosed at this time.(Smith,
Anderson, Kenneth N., ed. Mosby s Medical, Nursing and
Allied Health — 4th Edition
St. Louis: Mosby, 1994: 112.
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Imperfecta Acta Obstetricia et
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Children With Osteogenesis Imperfecta: A Ten-Year
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Medicine New York: McGraw Hill,
Jackson, Debra B., and Saunders, Rebecca B. Child Health
J.B. Lippincott, 1993: 1696-1699.
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Sturdy Spirit Independent
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