Osteogenesis Imperfecta Osteogenesis 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, laxity in the ligaments, and spinal deformities.(Binder, 386). Other collagen-containing skeletal 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. Osteogenesis imperfecta is still not completely understood, and while there has been advances in diagnosing the disease, treatment is still limited.
Osteogenesis imperfecta is the result of mutations in the genes that code 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 dramatic outcomes of similar glycine mutations in either the alpha 1 (I) or the alpha 2(I) chains (Smith, 169). The clinical signs can be caused from defective osteoblastic activity and defective mesenchymal collagen (embryonic connective tissue) and its derivatives, such as sclerae, 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). 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 worm like appearance, forming small islands (Isselbacher, 2111). Type II is lethal in utero or shortly there afterbirth. The survivors live from just a few hours to several months.
The karyotypes 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 death is usually from intracranial hemorrhaging 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 is 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 an 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 (curvature of the spine) may cause respiratory impairment and predisposition to pulmonary infections. Popcorn-like deposits of mineral appear on the ends of long bones (Isselbacher, 2111). The symptoms of OI (types I, III, and IV) can appear when the child begins to walk, and decreases with age. The tendency of bone 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 increases the number of 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 almost translucent skin. Discolored (blue-gray or yellow-brown) and malformed teeth which break easily and are cavity prone are found in most 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 (Loeb, 755). Hearing loss by the age of 30-40 is the result of the pressure on the auditory nerve due to the deformity of its canal in the skull.
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 noteworthy. 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, 1699). 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 biochemical studies of cultivated fibroblasts from the fetus (Berge, 321). Diagnosis by analyzing DNA sequ …