Osteogenesis imperfecta
Introduction
Introduction to osteogenesis imperfecta Osteogenesis imperfecta is a rare congenital skeletal development disorder, also known as fragile bone disease or brittle bone-blue sclera-deafness syndrome. It is a group of systemic connective tissue diseases characterized by increased skeletal fragility and collagen metabolism disorders. The lesions are not limited to bones, but often involve other connective tissues such as eyes, ears, skin, teeth, etc., which are characterized by multiple fractures, blue sclera, progressive deafness, tooth changes, joint relaxation, and skin abnormalities. The disease is hereditary and familial, but a few are single cases. basic knowledge The proportion of illness: 0.008% - 0.009% Susceptible people: no specific population Mode of infection: non-infectious Complications: rib fractures hydrocephalus flat feet
Cause
Osteogenesis imperfecta
Genetic (30%):
The cause of this disease is unknown, it is congenital developmental disorder, male and female are equal, can be divided into congenital and delayed type. Congenital type refers to the onset in the uterus, and can be divided into fetal type and infant type. Most of them die, or die shortly after delivery. They are autosomal recessive, and those with delayed type are milder. They can be divided into children and adults. Most patients can survive for a long time and are autosomal dominant. More than % of patients have a family history.
The disease is an autosomal dominant or recessive inheritance, which can be a sporadic case. The transmission of the blue sclera is 100%. Hearing loss varies with age. The sporadic cases are often caused by new mutations, often associated with the age of parents.
Gene mutation (30%):
The occurrence of osteogenesis imperfecta is mainly due to mutations in the genes encoding the 1 or 2 procollagen (Pro- 1 or Pro- 2 ) chains of type I collagen (ie COL1A1 and COL1A2), resulting in type I collagen synthesis disorders. The amount of collagen in the connective tissue, especially the type I collagen, is reduced. Collagen is the main collagen component of tissues such as bones, skin, sclera and dentin, and the disease changes in these parts are obvious.
Other factors (30%):
Mainly in the formation of skin, tendons, bones, cartilage and other connective tissue, the main component of collagen dysplasia, some authors reported that the patient's collagen tissue in the proline is too much, when the patient takes oral proline, blood The peak of endogenous proline is lower than that of normal children.
In the bone aspect, the osteoblast production is reduced or the activity is reduced, and alkaline phosphatase cannot be produced, or both cases are combined, so that the subperiosteal osteogenesis and the endochondral ossification are hindered, and the osteogenesis cannot be performed normally. The change is that the trabecular bone in the cancellous and cortical bones becomes fine and calcified, and there are clusters of chondrocytes, cartilage-like tissues and calcified bone-like tissues, and calcium deposition of bones. Normally, the above pathological changes cause bone fragility and bone softening.
Prevention
Osteogenesis insufficiency prevention
The disease is an autosomal dominant or recessive inheritance, which may be a sporadic case. There are no effective preventive measures at present.
When you are giving birth, you should go to the hospital for consultation or testing, early detection and early treatment. Avoid neonatal osteogenesis imperfecta.
Complication
Osteogenesis imperfecta complications Complications, rib fracture, hydrocephalus, flat foot
Severe cases of death in the uterus, or death within 1 week after delivery, most due to intracranial hemorrhage, or due to secondary infection, if you can survive for 1 month, there is a possibility of long-term survival, in infancy, Many times of fractures, the main difficulty in treatment, after puberty, the number of fractures is gradually reduced, women's fractures after menopause have an increasing trend, although the fracture can be healed normally, but not found in time or due to treatment Improper occurrence of false joints is also a lot, pelvic deformity can make childbirth difficult, neurological complications, including hydrocephalus, cranial nerve compression and corresponding dysfunction, spinal deformity can cause paraplegia.
The most common disease is complicated fracture. Most children have multiple multiple fractures, and the younger the fracture age, the worse the prognosis. The fracture is most likely to cause bone morphology changes or bone morphology abnormalities, spine and thoracic changes:
(1) The vertebral body is generally flattened and is biconcave or wedge-like;
(2) The posterior process or lateral posterior approach with thoracic distortion, collapse, common in childhood, progressive aggravation until before and after puberty;
(3) may also be associated with multiple rib fractures, beaded ribs and chicken breasts, pelvic changes vary in severity, mostly triangular deformation, acetabular retraction or with hip varus.
The complications of this disease are also the nervous system, including hydrocephalus, the cranial nerve is compressed to produce corresponding dysfunction, and spinal deformity can cause paraplegia.
Congenital osteogenesis imperfecta often due to intracranial hemorrhage to the stillbirth, delayed osteogenesis insufficiency can cause repeated fractures, often formed into angular deformities, the formation of pseudo-arthrosis, etc., can occur valgus foot, flat feet, habitual joint dislocation is also more common, There are incomplete teeth, progressive deafness and so on.
Symptom
Symptoms of osteogenesis imperfecta Common symptoms Osteoporotic spiral fractures Posterior vertebral head enlargement of deafness and otosclerosis Children with repeated fractures Cardiac malformation Facial kyphosis
About osteogenesis imperfecta, there are currently
(1) Fetal type: The condition is serious, and many classification methods are common: according to the time of the first fracture, it is divided into congenital type and delayed type; according to the severity of the disease, it is divided into 3 types; Sillence is based on hereditary methods and clinical manifestations in 1979. Divided into four types, this classification is currently the most widely used.
1. According to the severity of the disease, the skull is ossified and has multiple fractures in the fetal period. Most of them are stillbirths or short-term death after birth.
(2) Infant type: less common, there may be fractures after birth, after a minor trauma, or even no trauma can cause multiple fractures, more women than men, blue sclera and ligament relaxation.
(3) juvenile type (late type): the disease is the lightest, there is no fracture at birth, prone to fracture in childhood, and there is a tendency to automatically improve after puberty. Deafness can be caused by ear sclerosis around 20 years old.
2. According to hereditary methods and clinical manifestations (Sillence) classification
Type I: autosomal dominant inheritance, clinical features are fragile bone, postnatal fracture, blue sclera, in which the normal teeth are type A, and the incomplete teeth are type B.
Type II: Autosomal recessive inheritance, which can die in the perinatal period. Survivors present with deep blue sclera, femoral deformities and beaded ribs.
Type III: autosomal recessive inheritance, fracture at birth, progressive bone aggravation due to multiple fractures, normal sclera and hearing.
Type IV: autosomal dominant inheritance, normal sclera and hearing, only manifested as fragile bone.
3. Clinical manifestations of osteogenesis imperfecta
The disease is characterized by skeletal dysplasia, osteoporosis, increased fragility and malformation, blue sclera and hearing loss, but the clinical differences are very large. In severe cases, multiple intrauterine fractures and deaths occur, and symptoms are mild to school age. And can survive to the advanced age, the widely used clinical classification method is the four classification of Sillence, Sillence et al (1979) from the genetics of the perspective of osteogenesis imperfecta into four types, this type of method has been recognized by the academic community Type 1 is autosomal dominant, blue sclera, only mild bone deformity; type 2 is equivalent to the congenital type of the past; type 3 is severe, many cases show delayed intrauterine growth, fractures occur after birth, clinical Severe osteoarthrosis occurs in the infancy, blue sclera in infancy, not significant in childhood, this type of patient can generally survive to adulthood; type 4 is autosomal dominant, but no blue sclera, moderate osteoarthritis Although there is no intrauterine growth delay, the general development rate is slow, short stature, repeated fracture is a feature of osteogenesis imperfecta, with transverse fractures, spiral fractures are the most common, about 15% of fractures In the metaphysis, there may be a large number of epiphyseal hyperplasia after fracture, most of which can heal, but often residual deformity. In the literature, there are a large number of bone hyperplasia after 4 long bone fractures, resulting in high discharge heart failure and a large number of bone dysplasia caused by interval. Syndrome reports that fracture nonunion is prone to occur in progressive deformities with progressive fractures. Type 3 is more than type 4, and local atrophy or proliferative changes may occur.
At the age of 4, 70% of children with type I osteogenesis imperfecta can walk independently, and 1/3 of type 4 children can walk or climb, while type 3 children can not stand alone at this time. At 10 years old, 80% Type 3 children can sit independently, 20% of children can walk a short distance, 50% of type 1 and type 4 children with defects in the formation of teeth, more than 80% of type 3 children with incomplete teeth, congenital Cardiac malformation is not uncommon in type 3, and individual cases have hearing impairment due to otosclerosis. Recently, there have been reports of kidney stones, renal papillary calcification and diabetes.
(1) Increased bone fragility can cause fractures due to minor injuries. Severe patients present with spontaneous fractures. Congenital types have multiple fractures at birth. Most of the fractures are green branches, with less displacement, less pain, and healing. Fast, relying on subperiosteal ossification to complete, and therefore often not noticed to cause a deformed connection, long bones and ribs are good sites, the deformity caused by multiple fractures further reduces the length of the bone, after the puberty, the fracture trend is gradually reduced.
(2) The blue sclera accounts for more than 90%. This is because the patient's sclera becomes translucent and the color of the choroid below it can be seen. The thickness and structure of the sclera are not abnormal. The translucency is due to collagen fibers. The nature of the organization has changed.
(3) Deafness often occurs in the age of 11 to 40 years old, accounting for about 25%. It may be caused by ear canal sclerosis. The humeral foot plate attached to the oval window is fixed due to the rigidity of the bone, but some people think that it is the auditory nerve. The bottom is under pressure.
(4) Excessive joint relaxation, especially the wrist and ankle joint, which is due to the development of collagen tissue in tendons and ligaments. It can also have knee valgus, flat feet, and sometimes habitual shoulder dislocation and dislocation of the humeral head.
(5) The muscles are weak.
(6) Skull dysplasia with severe head and face deformity, the head has a skin sensation at birth, the skull is wide, the parietal bone and occipital bone are prominent, the two bulges are bulging, the frontal bone is protruding, the ears are pushed downward, and the face is Inverted triangles, some patients with hydrocephalus.
(7) Tooth dysplasia Dentin cannot develop well, and both the deciduous teeth and the permanent teeth can be affected. The teeth are yellow or blue-gray, easy to lick and early detachment.
(8) Dwarf, which is due to the development of a shorter period than normal, plus the healing of multiple fractures of the spine and lower extremities.
(9) Increased skin scar width, which is also due to defects in collagen tissue.
Examine
Osteogenesis insufficiency
The auxiliary examination methods for this disease are mainly X-ray examination and laboratory examination:
1, X-ray inspection:
X-rays are mainly characterized by bone deficiency and generalized bone sparseness.
1 The long bones are slender, the trabecular bones are sparse, semi-translucent, the cortex is thin as a pencil, the medullary cavity is relatively large, and the cystic changes can be severe in severe cases. The two ends of the bone are swollen and scorpion-shaped, and there are many places. Old or fresh fractures, some have been deformed, the backbone is curved, some deformities are caused by muscle attachment, such as hip varus, the femur and tibia are arched, some patients will form a rich spherical shape after the fracture Osteophytes, the number of which is wide, so that people will be misdiagnosed as osteosarcoma, and some patients have thicker cortical bone, called "thick bone type", rare.
2 delayed calcification of the skull, thinning of the bone plate, humeral bulging, wide frontal humerus, relatively dense rock bone, flat skull base, poor calcification of the deciduous teeth, and stable development of permanent teeth.
3 The vertebral body is thin, double concave, and the trabecular bone is sparse. The intervertebral disc is double convexly compensatory and can have scoliosis or kyphosis.
4 The ribs are bent downward from the ribs, and multiple fractures are often seen. The pelvis is triangular and the pelvis becomes smaller.
Joints: There are four main changes:
One part of the patient may cause depression of the acetabulum and femoral head into the pelvis due to osteomalacia;
2 Intramembranous osteogenesis of the backbone can cause the bone to become thinner, but the cartilage calcification and cartilage osteogenesis are still normal, and the bone ends of the joints are relatively coarse;
In some patients, there were most calcifications in the epiphysis, which may be caused by the unabsorbed calcium in the cartilage during cartilage osteogenesis;
4 pseudo-articular joint formation, due to multiple fractures, the formation of cartilage defects at the fracture, X-ray film looks like a pseudo-articular formation.
Skeleton: Early and late-onset osteogenesis imperfect bone damage is different. Early-onset patients are often characterized by multiple fractures of the long bones with osteophyte formation and skeletal deformation. Late-onset patients have obvious osteoporosis and multiple fractures. The long bone is bent or the femur is short and thick and the "accordion" is changed. The backbone is too thin or the backbone is too thick. The bone is cystic or honeycomb-like. The long cortical defect is rough, the ribs are thinner, and the lower edge is irregular or curved. The finger is changed like peanut, the alveolar plate is absorbed, the scoliosis is convex, the vertebral body is flattened, or the upper and lower diameters of the vertebral body are increased. It can also be expressed as a small vertebral body, the pedicle is enlarged, the skull is thin, and the suture is present. Protrusion, occipital ptosis, the long-distance line of the long bones of the extremities has a large number of horizontal dense lines, the density of the periorbital cartilage disc is increased and uneven, MRI and CT examination can find lateogenesis imperfecta lesions (osteogenesis imperfecta) There is hyperplastic osteophyte formation, sometimes resembling a bone tumor.
2, ultrasound examination
Ultrasound examination of the fetal skeletal system can detect congenital bone development disorders early. Garjian's experience shows that three-dimensional ultrasound can obtain stereoscopic anatomical positioning, so it is better than two-dimensional ultrasound examination. The former is more likely to detect head, face and rib deformities.
3. Laboratory inspection:
Generally normal, sometimes there may be an increase in blood phosphatase, which may be due to increased osteoblast activity after traumatic fracture, and extremely severe plasma calcium and phosphorus reduction, but very rare.
Patients with blood calcium, phosphorus and ALP are generally normal, a small number of patients with ALP can also be increased, urinary hydroxyproline increased, some with amino acid urine and mucopolysaccharide urine, 2 / 3 patients with elevated serum T4, due to increased thyroxine, white blood cells Oxidative metabolism is hyperthyroidism with platelet aggregation disorder.
Diagnosis
Diagnosis of osteogenesis imperfecta
diagnosis:
The four main diagnostic criteria are:
1. Osteoporosis and bone fragility increase.
2. Blue sclera.
3. Dentinogenesis imperfecta.
4. Premature otoclerosis.
Two of the above four items, especially the first two, can be diagnosed, and combined with imaging examination can help diagnose.
Generally, it is not difficult. Sometimes it is different from severe rickets. The rickets are characterized by widening and blurring of the epiphyseal cartilage. The dry sputum is irregular to the calcified cartilage area, the boundary is unclear, and the metaphyseal end itself is cup-shaped widening. The sparseness of other bones is not as obvious as that of osteogenesis imperfecta. Clinically, it should be different from cartilage hypoplasia, congenital muscle relaxation, hypothyroidism and parathyroidism. Generally speaking, it is not difficult.
Some scholars believe that the key point in the diagnosis of this disease is the identification of achondroplasia.
Cartilage hypoplasia is a systemic symmetrical cartilage development disorder, mainly characterized by short and thin limbs but normal to normal pygmy deformity. Severe cartilage hypoplasia sonogram features: fetal head enlargement, double top diameter widening; rib thick and short The chest is narrow but the lower thoracic cavity is relatively enlarged; the abdomen is bulging and the abdominal circumference is enlarged; the fetal limbs are short, the long bones are short and thick, and the bones are often curved and the bone ends are enlarged; the amount of amniotic fluid is increased, and the limbs of the two deformed fetuses are short. However, the osteogenesis is incomplete, the bone density is reduced, the cortex is thin, the fracture is very easy, and the bone deformity and thoracic deformation caused by the fracture are different from the chondral hypoplasia.
In addition, it should be noted that this disease can cause bone deformity and fracture, osteophyte formation, so the X-ray diagnosis should be differentiated from osteosarcoma, rickets, abnormal bone fiber and congenital pseudoarthrosis.
1. Delayed juvenile osteoporosis, general osteoporosis, vertebral biconcave deformation or flat vertebral body, and lateral kyphosis and easy fracture of the spine, similar to osteogenesis imperfecta; but the latter still has a large head The lateral humerus protrudes from the sides, the flat skull base, the face is small in triangle, the blue sclera, the multiple suture bones, and the family history are different from the former.
The diagnosis of type I OI is sometimes very difficult. I should think of type I OI in the case of osteoporosis in adolescents or severe osteoporosis in perimenopause.
2. Bone softening and rickets without bone brittle and easy to fold, no blue sclera, blurred front of the mineralization with brush or cup mouth, widened cartilage disc, bone softening more common in pregnant or lactating women, with bone pain , serum calcium, phosphorus are reduced.
3. Patients with vitamin C deficiency also have osteoporosis, but there may be bleeding points under the skin, between the muscles and the epithelium. There may be severe pain and pseudo-sputum, and calcification may occur after the fracture is healed.
4. Osteosarcoma osteogenesis patients with fractures may have a large number of osteophytes, most of which are benign, only a few have erythrocyte sedimentation and elevated blood ALP, if necessary, bone biopsy can be identified.
5. Hyperactivity of joints Joint relaxation and hyperactivity are one of the characteristics of OI and should be associated with other collagen-deficient diseases that cause this change, such as benign joint hyperactivity syndrome, Morquio syndrome, Ehlers-Danlos syndrome, Marfan syndrome, Larsen syndrome, etc., in addition, special types of OI can be expressed as Cole-Carpenter syndrome, or adolescent osteoporosis, Ehlers-Danlos syndrome, OI combined with primary hyperparathyroidism, OI combined teeth Dentinogenesis imperfecta (DI), OI-like syndrome, should be noted for identification.
