Osteogenesis imperfecta - Clinicals, Diagnosis, and Management

Genetic & Congenital disorders

Clinicals - History

Fact Explanation
Multiple fractures, pathological fractures occur due to trivial trauma Osteogenesis imperfecta is a genetic disorder causing qualitative or quantitative defect in type 1 collagen which forms the bone matrix . So the bones that are formed are dysplastic causing it to break even with minimal force. Bone fragility is severe in type II and III, moderate in IV and mild in type I. Type 1 is the most commonest form. . In type II usually the child dies during or shortly after birth. Multiple fractures, pathological fractures occur due to trivial trauma
Osteogenesis imperfecta is a genetic disorder causing qualitative or quantitative defect in type 1 collagen which forms the bone matrix . So the bones that are formed are dysplastic causing it to break even with minimal force. Bone fragility is severe in type II and III, moderate in IV and mild in type I. Type 1 is the most commonest form. . In type II usually the child dies during or shortly after birth.
Short stature More prominent in type III and IV.
Micro fractures on the growth plates following minor trauma leads to disturbed enchondral ossification. Which ultimately results in disturbed growth.
Also the involvement of the spine is also an important factor for reduced truncal growth. it is due to multiple compression fractures of the vertebral bodies and progressing spinal deformities. this usually starts after 6 years
Short stature
More prominent in type III and IV.
Micro fractures on the growth plates following minor trauma leads to disturbed enchondral ossification. Which ultimately results in disturbed growth.
Also the involvement of the spine is also an important factor for reduced truncal growth. it is due to multiple compression fractures of the vertebral bodies and progressing spinal deformities. this usually starts after 6 years
Recurrent pulmonary infections Most of them have spinal deformities such as thoracic scoliosis reducing pulmonary function thereby increase pulmonary morbidity during adulthood. Recurrent pulmonary infections
Most of them have spinal deformities such as thoracic scoliosis reducing pulmonary function thereby increase pulmonary morbidity during adulthood.
Presenile Hearing loss (progressively worsens) - Commonly conductive and mixed hearing loss seen. but also small percentage have sensorineural hearing loss. Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius . Presenile Hearing loss (progressively worsens) - Commonly conductive and mixed hearing loss seen. but also small percentage have sensorineural hearing loss.
Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius .
Limb deformities - Difficulty in ambulation Due to multiple fractures varies types of limb deformities are seen. Limb deformities - Difficulty in ambulation
Due to multiple fractures varies types of limb deformities are seen.
Lax joints Ligaments also contain type 1 collagen in their matrix . so defective collagen leads to defective ligaments which cannot maintain the joint integrity. Lax joints
Ligaments also contain type 1 collagen in their matrix . so defective collagen leads to defective ligaments which cannot maintain the joint integrity.
Defective dentition- discolored teeth (blue gray/ yellow brown color), weak fragile teeth (seen in both primary and secondary teeth) This is also known as Dentinogenesis imperfecta . Dentin which is the calcified part of the tooth which gives the color to the teeth since the enamel is translucent. Dentin also consist type 1 collagen in its matrix which becomes weak in Osteogenesis imperfecta . Defective dentition- discolored teeth (blue gray/ yellow brown color), weak fragile teeth (seen in both primary and secondary teeth)
This is also known as Dentinogenesis imperfecta . Dentin which is the calcified part of the tooth which gives the color to the teeth since the enamel is translucent. Dentin also consist type 1 collagen in its matrix which becomes weak in Osteogenesis imperfecta .
Cardiovascular abnormalities , Congenital cardiac defects and acquired heart defects such as aortic root dilatation, aortic insufficiency, mitral valve prolapse are important extra skeletal manifestations of Osteogenesis imperfecta.
Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood.
Cardiovascular abnormalities ,
Congenital cardiac defects and acquired heart defects such as aortic root dilatation, aortic insufficiency, mitral valve prolapse are important extra skeletal manifestations of Osteogenesis imperfecta.
Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood.
Renal manifestations - urinary stone disease Renal stones formation and renal papillary calcification is also seen in childhood Osteogenesis imperfecta. Renal manifestations - urinary stone disease
Renal stones formation and renal papillary calcification is also seen in childhood Osteogenesis imperfecta.
Neurological manifestations- seizure disorder, headache,features of brain stem compression such as lower cranial nerve dysfunction, quadriparesis, ataxia, nystagmus etc Hydrocephalus, basilar invagination and cerebral atrophy are seen in Osteogenesis imperfecta. Basilar invagination leads to compression of the brain stem. Also skull fracture and seizure disorder may also lead to the neurological manifestations. Neurological manifestations- seizure disorder, headache,features of brain stem compression such as lower cranial nerve dysfunction, quadriparesis, ataxia, nystagmus etc
Hydrocephalus, basilar invagination and cerebral atrophy are seen in Osteogenesis imperfecta. Basilar invagination leads to compression of the brain stem. Also skull fracture and seizure disorder may also lead to the neurological manifestations.
Family history of Osteogenesis imperfecta It is an inherited genetic condition due to mutation of COL1A1, COL1A2 genes which are type I collagen forming protein coding genes resulting in quantitative or qualitative defects of type 1 collagen. 95% is inherited in an autosomal dominant fashion and the rest account to autosomal recessive pattern and new mutations. .
When a parent has the disease there is a 50% chance and if a sibling has the disease chance varies from 0-50% due to the mosaic pattern in parent.
Family history of Osteogenesis imperfecta
It is an inherited genetic condition due to mutation of COL1A1, COL1A2 genes which are type I collagen forming protein coding genes resulting in quantitative or qualitative defects of type 1 collagen. 95% is inherited in an autosomal dominant fashion and the rest account to autosomal recessive pattern and new mutations. .
When a parent has the disease there is a 50% chance and if a sibling has the disease chance varies from 0-50% due to the mosaic pattern in parent.
Easy bruising Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII. Easy bruising
Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII.

Clinicals - Examination

Fact Explanation
Tinged sclera - blue/ violet It is due to an optical effect. Type1 collagen is a component of matrix of sclera as well . Defective collagen synthesis causes thinning of sclera. So the darker uveal color is brought out when a light is going through sclera. Tinged sclera - blue/ violet
It is due to an optical effect. Type1 collagen is a component of matrix of sclera as well . Defective collagen synthesis causes thinning of sclera. So the darker uveal color is brought out when a light is going through sclera.
Anthropometry - reduced height, with relatively short trunk (short sitting height)and disproportionately increased head size Since production of type 1 collagen is defective which is needed in the formation of bone matrix growth will also be affected.
Disproportionate short stature (Trunk length affected than limb length) is mainly due to the involvement of spine. Spine can have platyspondyly (radiographic characteristic where the vertebral bodies are flattened throughout the axial skeleton) or progressive shortening of axial skeleton can occur following spinal deformities
Anthropometry - reduced height, with relatively short trunk (short sitting height)and disproportionately increased head size
Since production of type 1 collagen is defective which is needed in the formation of bone matrix growth will also be affected.
Disproportionate short stature (Trunk length affected than limb length) is mainly due to the involvement of spine. Spine can have platyspondyly (radiographic characteristic where the vertebral bodies are flattened throughout the axial skeleton) or progressive shortening of axial skeleton can occur following spinal deformities
Spinal deformities - kyphosis/ scoliosis Scoliosis is commonly seen among OI patients but secondary kyphosis can also occur due multiple compression fractures of vertebral bodies. Spinal deformities - kyphosis/ scoliosis
Scoliosis is commonly seen among OI patients but secondary kyphosis can also occur due multiple compression fractures of vertebral bodies.
Joint laxity The ligaments also contains type 1 collagen in their connective tissue matrix. In Osteogenesis imperfecta there is either qualitative or quantitative defect in production of type 1 collagen. this leads to defective ligament integrity. Joint laxity
The ligaments also contains type 1 collagen in their connective tissue matrix. In Osteogenesis imperfecta there is either qualitative or quantitative defect in production of type 1 collagen. this leads to defective ligament integrity.
Hearing defects - conductive/ sensorineural/ mixed Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius Hearing defects - conductive/ sensorineural/ mixed
Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius
Triangular face. A characteristic feature that occurs due to due to overdevelopment of the head and underdevelopment of the facial bones. Triangular face.
A characteristic feature that occurs due to due to overdevelopment of the head and underdevelopment of the facial bones.
Macrocephaly Head circumference shows abnormal growth pattern which frequently cause macrocephaly . Also due to basilar invagination there is compression of brain stem. This may lead to hydrocephalus as well. Macrocephaly
Head circumference shows abnormal growth pattern which frequently cause macrocephaly . Also due to basilar invagination there is compression of brain stem. This may lead to hydrocephalus as well.
Barrel chest Because of the spinal deformities there is some amount of reduction of pulmonary functions which may lead to compensatory increase if the chest circumference. Barrel chest
Because of the spinal deformities there is some amount of reduction of pulmonary functions which may lead to compensatory increase if the chest circumference.
CVS examination may reveal cardiovascular system abnormalities Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood
Abnormalities such as congenital heart disease such as aortic stenosis, ASD, tetralogy of Fallot and acquired defects such as Mitral valve prolapse, aortic insufficiency.
CVS examination may reveal cardiovascular system abnormalities
Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood
Abnormalities such as congenital heart disease such as aortic stenosis, ASD, tetralogy of Fallot and acquired defects such as Mitral valve prolapse, aortic insufficiency.
Neurological manifestations - features of brain stem compression such as lower cranial nerve palsies, ataxia, nystagmus, Spinal compression, unexplained long tract signs. Neurological manifestations are caused by basilar invagination , skull fractures, cerebral atrophy etc. Neurological manifestations - features of brain stem compression such as lower cranial nerve palsies, ataxia, nystagmus, Spinal compression, unexplained long tract signs.
Neurological manifestations are caused by basilar invagination , skull fractures, cerebral atrophy etc.
Bruises Due to their tendency to bruise easily. Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII. Bruises
Due to their tendency to bruise easily. Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII.

Investigations - Diagnosis

Fact Explanation
Antenatal ultrasonography (Trans abdominal / trans vaginal)- limb length abnormalities (eg. bowing), multiple fractures inutero, compressible cranium, transparent calvaria. micromelia etc Limb length abnormalities and multiple fractures in utero is seen in severe forms of Osteogenesis imperfecta from second trimester. Compressible and transparent cranium is seen due to low mineralization of the skull. But it is not diagnostic of Osteogenesis imperfecta
Non specific features such as intra uterine growth retardation, hydraminos can also be present.
milder forms may not be detected antenatally.
Antenatal ultrasonography (Trans abdominal / trans vaginal)- limb length abnormalities (eg. bowing), multiple fractures inutero, compressible cranium, transparent calvaria. micromelia etc
Limb length abnormalities and multiple fractures in utero is seen in severe forms of Osteogenesis imperfecta from second trimester. Compressible and transparent cranium is seen due to low mineralization of the skull. But it is not diagnostic of Osteogenesis imperfecta
Non specific features such as intra uterine growth retardation, hydraminos can also be present.
milder forms may not be detected antenatally.
Prenatal Diagnosis done using chorionic villus sampling within the first trimester OI shows autosomal dominance inheritance but new mutations are common and also certain types show recessive pattern. When a parent has OI there is a 50% chance, and if a sibling has the chance varies from 0- 50% because of the parental mosaicism..
Collagen synthesis analysis could be done using the cultured chorionic villus sampling which could only be done in type II,III,IV .
Mutation analysis could be done using the DNA obtained in chorionic villus sampling or amniocentesis. .
This should be in families who already have or had a child/ parent with osteogenesis imperfecta .
Prenatal Diagnosis done using chorionic villus sampling within the first trimester
OI shows autosomal dominance inheritance but new mutations are common and also certain types show recessive pattern. When a parent has OI there is a 50% chance, and if a sibling has the chance varies from 0- 50% because of the parental mosaicism..
Collagen synthesis analysis could be done using the cultured chorionic villus sampling which could only be done in type II,III,IV .
Mutation analysis could be done using the DNA obtained in chorionic villus sampling or amniocentesis. .
This should be in families who already have or had a child/ parent with osteogenesis imperfecta .
A full skeletal survey by plain radiographs. After birth at different stages of life its mostly diagnosed with clinical features and radiological examination. conventional radiography is the mainstay of diagnosing. More sophisticated investigations such as DNA tests are needed when the diagnosis cannot be made. A full skeletal survey by plain radiographs.
After birth at different stages of life its mostly diagnosed with clinical features and radiological examination. conventional radiography is the mainstay of diagnosing. More sophisticated investigations such as DNA tests are needed when the diagnosis cannot be made.
X ray - skull: shows wormian bones, platybasia, enlargement of frontal and mastoid sinuses. Significant number of Wormian bones are seen in most severe form of Osteogenesis imperfecta .
Platybasia which is abnormal flattening of the base of skull and basilar impression which is seen in CT are seen Osteogenesis imperfecta tarda which is the less severe form of the disease.
X ray - skull: shows wormian bones, platybasia, enlargement of frontal and mastoid sinuses.
Significant number of Wormian bones are seen in most severe form of Osteogenesis imperfecta .
Platybasia which is abnormal flattening of the base of skull and basilar impression which is seen in CT are seen Osteogenesis imperfecta tarda which is the less severe form of the disease.
Xray chest- fractured and beaded ribs, pectus carinatum, barrel chest Multiple rib fractures and repeated healing by callus formation produces fractured and continuously beaded ribs. .
Since there is chronic pulmonary insufficiency to increase the respiratory capacity the chest becomes barrel shaped.
Xray chest- fractured and beaded ribs, pectus carinatum, barrel chest
Multiple rib fractures and repeated healing by callus formation produces fractured and continuously beaded ribs. .
Since there is chronic pulmonary insufficiency to increase the respiratory capacity the chest becomes barrel shaped.
Pelvis x ray - Shepherd's crook deformity of the femurs, multiple fractures and dislocations, narrow pelvis, protrusio acetebuli Shepherd's crook deformity - coxa varus angulation of the proximal femur - occurs due to repeated fractures of proximal femur
Due to bone fragility
Pelvis x ray - Shepherd's crook deformity of the femurs, multiple fractures and dislocations, narrow pelvis, protrusio acetebuli
Shepherd's crook deformity - coxa varus angulation of the proximal femur - occurs due to repeated fractures of proximal femur
Due to bone fragility
X ray long bones- multiple fractures and excessive callus formation, popcorn bones, irregular and partially or completely absent growth plates in children Popcorn calcifications are multiple small radiolucent calcifications with sclerotic margins in epiphysis and metaphysis of long bones. Seen always around abnormal growth plates. They are detached fragments of growth plates following minor trauma which leads to micro fractures of the growth plates. X ray long bones- multiple fractures and excessive callus formation, popcorn bones, irregular and partially or completely absent growth plates in children
Popcorn calcifications are multiple small radiolucent calcifications with sclerotic margins in epiphysis and metaphysis of long bones. Seen always around abnormal growth plates. They are detached fragments of growth plates following minor trauma which leads to micro fractures of the growth plates.
spinal deformities such as scoliosis/ kyphosis,Vertebral compression fractures, cod fish vertebrae, platyspondyly Commonly progressive scoliosis is seen among OI patients but secondary kyphosis can also occur due to multiple compression fractures . Severity of the curvature is dependent on the severity of the disease and age. soft brittle bones of the vertebrae are prone to compression fractures. laxity of the vertebral ligaments also plays an important role in instability of the spine.
Pressure on the normal nucleus pulposes cause vertebrae to become biconcave in shape thus attain the cod fish vertebrae.
platyspondyly is the flattened vertebral bodies throughout the axial skeleton which is seen in the radiograph.
spinal deformities such as scoliosis/ kyphosis,Vertebral compression fractures, cod fish vertebrae, platyspondyly
Commonly progressive scoliosis is seen among OI patients but secondary kyphosis can also occur due to multiple compression fractures . Severity of the curvature is dependent on the severity of the disease and age. soft brittle bones of the vertebrae are prone to compression fractures. laxity of the vertebral ligaments also plays an important role in instability of the spine.
Pressure on the normal nucleus pulposes cause vertebrae to become biconcave in shape thus attain the cod fish vertebrae.
platyspondyly is the flattened vertebral bodies throughout the axial skeleton which is seen in the radiograph.
Skin biopsy - collagen synthesis analysis. Fibroblasts could be cultured and collagen synthesis could be analyzed with various methods. In OI it may show either quantitative defect or qualitative defect of type 1 procollagen . Quantitative defect is seen in less severe Osteogenesis imperfecta, and qualitative defect is seen in severe Osteogenesis imperfecta Skin biopsy - collagen synthesis analysis.
Fibroblasts could be cultured and collagen synthesis could be analyzed with various methods. In OI it may show either quantitative defect or qualitative defect of type 1 procollagen . Quantitative defect is seen in less severe Osteogenesis imperfecta, and qualitative defect is seen in severe Osteogenesis imperfecta
Bone densitomery - DEXA scan Shows decreased bone mineral density. Osteopenia is a characteristic feature of any type of OI. Can use to diagnose and monitor progression. Bone densitomery - DEXA scan
Shows decreased bone mineral density. Osteopenia is a characteristic feature of any type of OI. Can use to diagnose and monitor progression.
CT / MRI of brain - basilar invagination, hydrocephalus, ventral brain stem compression, syringomyelia/ syringobulbia can be seen rarely CT / MRI of brain -
basilar invagination, hydrocephalus, ventral brain stem compression, syringomyelia/ syringobulbia can be seen rarely
Metabolic screen The results are usually normal. This done to exclude other metabolic diseases. Metabolic screen
The results are usually normal. This done to exclude other metabolic diseases.
Genetic testing (mutation analysis) - to identify specific gene defects Genetic testing is done to identified mutation in COL1A1, COL1A2 which encodes type 1 procollagen chains. >90% of the patients have been estimated to have mutations in those two genes. But they do not cause type V, VI and VII Osteogenesis imperfecta.
Warranted only if diagnosis cannot be made by the usual History, examination, radiographs. Accuracy is high.
Genetic testing (mutation analysis) - to identify specific gene defects
Genetic testing is done to identified mutation in COL1A1, COL1A2 which encodes type 1 procollagen chains. >90% of the patients have been estimated to have mutations in those two genes. But they do not cause type V, VI and VII Osteogenesis imperfecta.
Warranted only if diagnosis cannot be made by the usual History, examination, radiographs. Accuracy is high.
Cervical spine - basilar invagination (it is a craniocervical junction abnormality. The tip of odontoid process projects above the foramen magnum into the cranium ) It is congenital or acquired. Where there is upward migration of the cervical spine. It is associated with platybasia where the base of skull is soft and flat and the laxity of ligaments in OI also contribute.
This leads to stenosis of foramen magnum and its associated sequelae explained in examination.
Cervical spine - basilar invagination (it is a craniocervical junction abnormality. The tip of odontoid process projects above the foramen magnum into the cranium )
It is congenital or acquired. Where there is upward migration of the cervical spine. It is associated with platybasia where the base of skull is soft and flat and the laxity of ligaments in OI also contribute.
This leads to stenosis of foramen magnum and its associated sequelae explained in examination.
Low dose CT with 3D reconstruction of the whole fetal skeleton. Done when termination of pregnancy is considered but the diagnosis is in doubt after USS. Done after 26 weeks. Will give a definite diagnosis. Low dose CT with 3D reconstruction of the whole fetal skeleton.
Done when termination of pregnancy is considered but the diagnosis is in doubt after USS. Done after 26 weeks. Will give a definite diagnosis.

Management - Supportive

Fact Explanation
Regular exercise To maintain good muscle power. Regular exercise
To maintain good muscle power.
Balanced diet To maintain adequate BMI Balanced diet
To maintain adequate BMI
Avoid steroid medication Patient/ parent should inform any doctor they consult regarding their condition, so that steroids can be avoided which causes secondary osteopenia. Avoid steroid medication
Patient/ parent should inform any doctor they consult regarding their condition, so that steroids can be avoided which causes secondary osteopenia.
Physiotherapy to improve muscle strength and also to reduce contractures Physiotherapy
to improve muscle strength and also to reduce contractures
Pain management Multiple fractures and deformities can cause pain to the child which should be ideally managed to give a better quality of life. Pain management
Multiple fractures and deformities can cause pain to the child which should be ideally managed to give a better quality of life.
Orthosis to improve mobility of the patient. Fractures and deformities may limit the child's mobility and other functions. proper orthotic support can improve the functional status of the child thus prevent disuse muscle weakness and disuse osteopenia Orthosis to improve mobility of the patient.
Fractures and deformities may limit the child's mobility and other functions. proper orthotic support can improve the functional status of the child thus prevent disuse muscle weakness and disuse osteopenia
Genetic counseling to parents Since it is an inherited condition as explained in the history genetic counseling is needed to parent sin planning the next pregnancy and to make an antenatal diagnosis using the methods explained in investigations and do the needful. When a sibling has the disease chance in next child varies from 0-50% due to the mosaic pattern in parent Genetic counseling to parents
Since it is an inherited condition as explained in the history genetic counseling is needed to parent sin planning the next pregnancy and to make an antenatal diagnosis using the methods explained in investigations and do the needful. When a sibling has the disease chance in next child varies from 0-50% due to the mosaic pattern in parent

Management - Specific

Fact Explanation
No curative treatment is only option is symptomatic treatment. A multidisciplinary team approach is needed for proper management. Since it is a genetic disease there is no specific treatment to cure this disease. type II disease lethal in utero or just after birth. Type III disease is severe which leads to death mostly due to respiratory complications. No curative treatment is only option is symptomatic treatment.
A multidisciplinary team approach is needed for proper management. Since it is a genetic disease there is no specific treatment to cure this disease. type II disease lethal in utero or just after birth. Type III disease is severe which leads to death mostly due to respiratory complications.
Bisphosphonates - Cyclical Intravenous pamidronate. Bisphosphonates are pyrophosphate analogue which binds to hydroxy apatite in bones thereby inhibit osteoclast mediated bone resorption. This leads to increase in bone mineral density thus reduce the risk of fractures. . Though their benefits and short term safety are well explained long term effects are not well studied Bisphosphonates - Cyclical Intravenous pamidronate.
Bisphosphonates are pyrophosphate analogue which binds to hydroxy apatite in bones thereby inhibit osteoclast mediated bone resorption. This leads to increase in bone mineral density thus reduce the risk of fractures. . Though their benefits and short term safety are well explained long term effects are not well studied
Proper management of fracture - eg. intra medullary rodding of long bones Early proper management of fracture improves healing and reduces deformities. Proper management of fracture - eg. intra medullary rodding of long bones
Early proper management of fracture improves healing and reduces deformities.
surgical management of basilar herniation and . Basilar herniation as explained in the investigation can cause medullary compressive symptoms which could be corrected by surgery and improve the child's condition surgical management of basilar herniation and .
Basilar herniation as explained in the investigation can cause medullary compressive symptoms which could be corrected by surgery and improve the child's condition
Correction of scoliosis Correction will be difficult because of their bone fragility. curving of spine starts around 5-6 years and progress rapidly. Early bracing, though effective way to control scoliosis/ kyphosis, in OI patients with soft rib cage may compress the chest wall increasing the pulmonary compromise. Correction of scoliosis
Correction will be difficult because of their bone fragility. curving of spine starts around 5-6 years and progress rapidly. Early bracing, though effective way to control scoliosis/ kyphosis, in OI patients with soft rib cage may compress the chest wall increasing the pulmonary compromise.
Proper dental management Dentinogenesis imperfecta is part of the disease in certain types of disease. they have poor dentin development. Thus cause frequent breaking of the teeth. so they need to protect as well as manage any teeth fractures. May need implantation of the teeth as well. Proper dental management
Dentinogenesis imperfecta is part of the disease in certain types of disease. they have poor dentin development. Thus cause frequent breaking of the teeth. so they need to protect as well as manage any teeth fractures. May need implantation of the teeth as well.
Early identification and treatment of respiratory comlications Respiratory disease is a common morbidity and a common cause of death. Early identification and treatment of respiratory comlications
Respiratory disease is a common morbidity and a common cause of death.

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