Developmental Malformations

Updated 09.05.2020
Released 11.13.2001
Expires For CME 09.05.2023

Osteogenesis imperfecta type II: cerebral dysgenesis

Author: Joseph R Siebert PhD

Introduction

Overview

In this article, the author provides the pathologic and clinical details of the perinatal lethal and usually dominant form (type II) of osteogenesis imperfecta. New mutations responsible for recessive forms are described. Abnormalities in collagen, which develop from hundreds of different mutations in type I collagen genes, lead to exceptionally brittle bones that become markedly shortened by characteristic, telescoping fractures. The calvaria is thinned, and the brain is enlarged and altered by a host of changes, chiefly neuronal migrational defects. Additional anomalies are recognized and vary among the different types of osteogenesis imperfecta. New forms of treatment are reviewed, and unresolved issues are identified.

Key points

	• Osteogenesis imperfecta consists of a diverse collection of congenital and heritable (autosomal dominant or, less often, recessive) disorders of connective tissue, which result in fragile and easily fractured bone.
	• Osteogenesis imperfecta type II is a perinatal lethal form that involves approximately 4% of all patients with osteogenesis imperfecta.
	• In osteogenesis imperfecta type II, cerebral dysgenesis takes several forms but often involves neuronal migration defects or subcortical angiomatosis.
	• In patients with nonlethal forms, therapy continues to be refined; in addition to surgery, medical treatment of bone fragility includes the use of bisphosphonate and, in the early stages of development, pre- and postnatal stem cell transplantation.

Historical note and terminology

Osteogenesis imperfecta, a congenital disease characterized by defective bone formation, has been recognized and studied for many decades. One of the earliest cases appeared in Vrolik’s Handbook of Pathological Anatomy, published between 1842 and 1844 (12). In this “brittle bone disease,” bones are abnormally thin or broad and fracture easily, often giving pathognomonic appearances radiographically. Traditionally, cases have been categorized into 4 types with additional subtypes. Some now consider osteogenesis imperfecta to exist in up to 8 forms (136; 103). For purposes of this review, a thorough tabulation of the many details of these types seems unwarranted, and discussion will be oriented toward changes associated with Type II. The group of disorders constituting osteogenesis imperfecta is heritable and presents as autosomal recessive or autosomal dominant conditions. Type II, the perinatal lethal type, can follow either pattern, but the dominant form is considerably more common. Type II is rare within the spectrum of osteogenesis imperfecta patients. In 1 study of 57 patients, only 2 had Type II (138). Type II osteogenesis imperfecta has 3 variants: A, B, and C (158). In Type IIA, long bones are short and broad, with a collapsed or telescoped appearance of multiple fractures; tibiae are angulated; ribs are focally thickened in a manner described as “continuously beaded.” In Type IIB, long bones are similarly altered, but ribs are normal or only partially beaded. In Type IIC, long bones are thin and rectangular with numerous fractures; ribs are thin and beaded. In concert with molecular and other developments, workers continue to suggest modifications to this classification (175).

Clinical manifestations

Presentation and course

Patients with osteogenesis imperfecta have short, fragile bones, abnormal (ie, blue) sclerae, variable degrees of deafness, hyperextensible joints, decreased elasticity of skin, and incomplete formation of dentin (158; 75). In affected fetuses or infants, the skull is larger than expected. Craniocerebral fractures or other injuries may occur in the prenatal period, and as with postnatal cases, must be differentiated from injuries sustained as a result of abuse (195). A number of pathologic changes may occur, most likely because of the rather widespread presence of collagen type 1 in the heart (08). The heart and major vessels can be altered by short, fragile chordae; malformed atrioventricular valves; mitral and aortic regurgitation; decreased collagen, elastic fibers, and myxoid change; and disorganized collagen with or without calcification. Valvular heart disease may require valve replacement and even coronary artery bypass grafting if the aortic valve is involved (24). In a large Danish study (N = 575), no association with aortic aneurysm or dissection was identified (54). Lethality in the perinatal period is due to respiratory insufficiency; 1 report of a 25-day survival is available (10).

Changes in the brain may occur as primary dysplasias or secondary to bone alterations. Wormian bones occur with increased frequency in osteogenesis imperfecta and have diagnostic utility but are not associated with particular abnormalities in the CNS (155; 18). Anencephaly has been reported in a fetus with osteogenesis imperfecta, but the finding appears to be coincidental (29). Likewise, a single case of osteogenesis imperfecta with holoprosencephaly has been reported (183). A number of skeletal dysplasias (among which are osteogenesis imperfecta, achondroplasia, spondyloepiphyseal dysplasia, acro-osteolysis, and Hurler syndrome) are associated with a deformation in the cranial base known as basilar impression or secondary basilar invagination (133; 106). Although the change is rare in osteogenesis imperfecta and seems to be restricted to patients with milder forms of the disease, it can have serious consequences. Basilar impression is initiated with softening, or even fracturing, of cranial bones. The squamous portion of the occipital bone folds inward, resulting in abnormal upward curvature of the foramen magnum and elevation of the floor of the posterior fossa. Deformations in contiguous bones result in accentuation of the cranial base angle and craniocervical angle (106). With basilar invagination, the odontoid process extends to the level of or into the foramen magnum; this change and platybasia (flattened cranial base) are present in types III and IV (87). Neurologic symptoms depend on the severity of the invagination; ventricular dilatation can be asymptomatic; elevation of the brain stem and increased traction of the cervical spinal cord may result in dysfunction and myelopathy; cranial nerve palsies may develop secondary to displacement of the brain stem; and cerebellar compression may lead to hydrocephalus, syringohydromyelia, or hindbrain herniation. Abnormalities of the cranial base are found in about one fifth of patients and one half of patients with markedly reduced height (40). Vasculopathic changes (stenoses and prethrombotic occlusion) have been reported in the cerebral arteries of a patient with osteogenesis imperfecta type 4 and are thought to be due to vascular fragility arising from collagen defects (02). It is unclear if this complication affects patients with type II disease.

Hydrocephalus may be of prenatal onset with associated fractures of the occipital bone and narrowing of the foramen magnum (83). One form of perinatally lethal osteogenesis imperfecta has been associated with microcephaly and cataracts in 3 siblings (30). The brains in all were immature for age and showed flattened gyri. Neuronal migrational defects and other forms of CNS dysgenesis are described in the pathogenesis and pathophysiology section.

Prognosis and complications

As stated, individuals with type II osteogenesis imperfecta die during or shortly after the perinatal period, with only the rare exception (04). Some 60% die on the first day of life, whereas 80% die in the first week; survival beyond 1 year is very rare (32). Usually, death comes from respiratory insufficiency, which is due to the combined effects of a dysfunctional thorax (secondary to chest fractures and/or deformities) and pulmonary hypoplasia.

Patients with other forms of osteogenesis imperfecta may also manifest decreased pulmonary function, which appears to be intrinsic to the disease itself or secondary to chest deformities rather than scoliosis (28). Some individuals live a normal life span (especially those with milder conditions) or die of complications related to the disease (respiratory insufficiency or infection; cardiac death, sometimes related to kyphoscoliosis; basilar invagination; intracranial bleeding) (104). Deformities of the spinal column occur most often in the midthoracic region where they affect lung function as well as height (187). Compression fractures may be treated either surgically or medically (92). Mild trauma can have serious consequences in patients with osteogenesis imperfecta, from both orthopedic and cerebral aspects. Muscle strength, range of motion, and gait are affected by the severity of fractures, amount of bone deformity, and success in treatment (26). Subdural hematoma is rare, despite the relative frequency of skull fractures, and has also been reported in the absence of trauma or anticoagulation (151). One study of bleeding tendency in patients uncovered no underlying bleeding disorders or problems with coagulation, instead suggesting that vessel fragility could be a factor (67). Trigeminal neuralgia is a rare complication of basilar invagination. Treatment by percutaneous balloon decompression following cannulation of the foramen ovale is especially difficult when the cranial base is distorted (73; 146). Temporomandibular dysfunction is recognized, and associated malocclusions is more prevalent in patients with moderate to severe osteogenesis imperfecta (Ortega et al 2007; 20).

Clinical vignette

Type II osteogenesis imperfecta was observed in a male fetus delivered by labor induction at 20 weeks.

Osteogenesis imperfecta type II in 20-week fetus

Note the short limbs and comparatively large head in this hydropic fetus. (Contributed by Dr. Joseph Siebert.)

No pertinent familial history was obtained. Prenatal ultrasound examination documented skeletal changes consistent with type II osteogenesis imperfecta. Gross autopsy and culture of fetal cells confirmed the diagnosis. A point mutation (substitution of valine for glycine at amino acid 187) was identified within the triple helical region of the a1(I) chain of type I collagen. There was no evidence for a deletion or insertion.

Autopsy findings consisted of growth retardation; shortened, deformed limbs; megalencephaly, with extensive subarachnoid cerebellar hemorrhage; markedly deficient calvarial ossification; multiple telescoping fractures of long bones with marked shortening; multiple rib fractures; and pulmonary hypoplasia (the lung weighed one-half of the expected weight for gestational age). No cardiac or other changes were observed grossly. Microscopically, the fractures showed disorganization typical of various ages and inadequate ossification in calvarial bones.

Osteogenesis imperfecta type II in 18-week fetus (alizarin stain)

Note rib fractures with shortened long bones with multiple telescoping fractures. (Contributed by Dr. Joseph Siebert.)

Biological basis

Etiology and pathogenesis

Cases of type II osteogenesis imperfecta are autosomal dominant or (rarely or at times erroneously thought to be) recessive and result from mutations in 1 of the type I collagen genes (COL1A1 or COL1A2) localized at 7q21-7q22 or 17q21-17q22 (121). Mutations in CRTAP and LEPRE1 have been identified in types VII and VIII and associated with the recessive form (103; 122; 14; 107). Mutations in at least 18 additional genes may also cause the phenotypic changes of osteogenesis imperfecta (168). Several families with recessive osteogenesis imperfecta caused by mutations in WNT1 have been identified (135). Mutations in the gene encoding the RER protein FKBP65 (which is involved in type I procollagen folding) have been found to cause autosomal recessive osteogenesis imperfecta (01). In general, mutations in non-collagenous genes are responsible for less than 10% of cases and result in altered collagen synthesis or bone development; these mutations may be autosomal dominant or recessive or X-linked (153; 143).

Osteogenesis imperfecta I is a genetically determined condition that results from reduced amounts of type I collagen. This, in turn, develops from a nonfunctional allele, the result of mutations in the genes that code for type I collagen. Type I collagen is the principal matrix protein in bone, dentin, sclerae, and ligaments, accounting for the involvement of these tissues in osteogenesis imperfecta. Type II osteogenesis imperfecta is caused by mutations in either COL1A1 or COL1A2. Between these 2 genes, hundreds of mutations have been identified (84; 190). Combined, mutations in the 2 genes are responsible for about 95% of all clinically ascertained patients (177). Many of these are substitutions for glycine, but a variety of single-base deletions, splice junction mutations, and insertions have also been described in the type II form (185). It appears that defects at the C-terminal end of the collagen protein are associated with more severe forms of osteogenesis imperfecta (190). One consequential metabolic change is decreased activity of prolidase, an enzyme necessary for collage synthesis and cell growth; associated with this change are decreases in the expression of beta1 integrin and insulin-like growth factor-I receptors, important in the up regulation of prolidase activity (61). Overglycosylation of collagen may be related to the structural integrity of bone (51).

Most cases represent dominant mutations, and recessive inheritance appears to be rare. Supporting evidence for recessive cases has been controversial. A number of cases resulting from consanguineous matings have been reported, but in some of these, the diagnosis of osteogenesis imperfecta is debated, or the parents are thought to be mosaic. However, newly designated forms appear to be autosomal recessive and due to mutations in the CRTAP and LEPRE1 genes; the phenotypes tend to be severe and overlap with types II and III (110; 14). These 2 genes appear to be responsible for approximately 5% of cases of osteogenesis imperfecta type II (23). Some dominant cases may manifest mild expressivity, thus, complicating diagnosis. All of this suggests that the overall recurrence risk is much lower (ie, 4% to 8%) than the 25% that would be expected from recessive inheritance alone (170). Some of this uncertainty could stem from the possibility that noncollagenous loci are involved in rare and still unclassified forms of osteogenesis imperfecta (177). In fact, the phenotype of patients with noncollagen genes overlaps with both type II and type III osteogenesis imperfecta (60).

Histologic and electron microscopic changes are recognized in dentin (48), and the genetics remain under study (82). The term “dentinogenesis imperfecta” has been applied to those defects observed in cases of osteogenesis imperfecta associated with collagen defects. The reduced level or altered activity of alkaline phosphatase is thought to lead to dysfunction of osteoblasts, whereas structurally abnormal collagen may fail to provide the scaffolding necessary for calcium deposition (149; 148; 48).

A number of dysgenetic changes have been observed in the brains of fetuses with osteogenesis imperfecta type II (178; 52). These include migrational defects such as agyria, abnormal neuronal lamination, nests of neuroblasts in white matter, and hippocampal malrotation. Explanations for these migrational defects are understood incompletely but may relate to the observation that type I collagen promotes neuritic maturation. Vascular microcalcifications have also been observed in the CNS of patients with osteogenesis imperfecta type II and have been associated with proteoglycan and type I and type IV collagen deposits (178). Subcortical angiomatosis has been reported as well (126). Changes such as periventricular leukomalacia and diffuse hemorrhage have been described, but these disorders do not appear to be directly related to osteogenesis imperfecta.

Brtl and OIM mouse models for osteogenesis imperfecta are proving valuable for understanding the genetic mechanisms involved in pathogenesis (89; 88).

Epidemiology

Both the incidence and prevalence of osteogenesis imperfecta have been reported, but the numbers vary widely. For example, the incidence has been given as 0.17 per 10,000 live births to 0.5 per 10,000 live births, though others have provided estimates as high as 4.5 per 10,000 births (15). With increased use of molecular diagnosis, the accuracy of this estimate should increase. However, the use of pregnancy termination complicates such efforts and may have particular import in the study of type II osteogenesis imperfecta. In many states, death certificates are required only for fetuses with a gestational age of 20 weeks or more; thus, younger fetuses would not be included in the state's vital statistics.

Workers have begun to examine the evolutionary histories of gene mutations, which appear to vary among different ethnic groups (37). For Latin America (studied from 1978 to 1983), the prevalence of all forms of osteogenesis imperfecta has been given as 0.4 per 10,000 live births (123). In 1 large county in Denmark (studied from 1970 to 1983), the point (birth) prevalence was 2.18 per 10,000 live births, and the population prevalence was 1.06 per 10,000 inhabitants (06). Interestingly, the prevalence of osteogenesis imperfecta among blacks in southern Africa is considerably higher than whites and seems to reflect an increased gene frequency that arose at least 2000 years ago (17; 179). Some 35 mutations in COL1A1 and COL1A2 have been reported in 67 Korean patients (91). Cases have been reported infrequently in China, but reasons for this are unclear (193). Epidemiologic data are lacking for autosomal recessive forms (16).

Maternal age does not appear to have an effect on the appearance of cases. However, paternal age is increased slightly in some, but not all, samples. Mean age (31.15 ± 9.25) was above that of controls in a Latin American, but not Italian, sample (124). In a study of sporadic cases in Scotland, mean age of fathers was 0.87 years greater than expected and relative risk was 1.62 (22). Paternal age was not significantly different among the different subtypes of osteogenesis imperfecta.

Differential diagnosis

Osteogenesis imperfecta must be distinguished from hypophosphatasia, the reduction in activity of alkaline phosphatase in tissues (including bone and cartilage) and serum. In this latter condition, the neurocranium fails to ossify, and the skull is soft; the skeleton is mineralized inadequately, and lone bones are shortened and curved to the point of angulation; diaphyseal spurs and fractures are observed. In newborns with hypophosphatasia, bone formation can be exceedingly scant. Ultrasound examination can, therefore, be quite helpful in differentiating the conditions, in addition to molecular methods (194). Both perinatal lethal and infantile forms of hypophosphatasia can occur, and both may occur in the same family (192; 95).

Chondrodysplasia punctata manifests abnormal mineralization of bones during gestation, and, thus, may give the appearance of osteogenesis imperfecta type II by prenatal ultrasound (157).

Patients with infantile copper deficiency may suffer from anemia, vomiting, apnea, hepatomegaly, and "temporary brittle bone disease" and, thus, mimic osteogenesis imperfecta (130).

Hypomineralization of the calvaria in early gestation can give the sonographic appearance of “acrania,” a term erroneously used by some authors to describe acalvaria (186; 108). The sonographic differential in cases of acalvaria or hypocalvaria includes osteogenesis imperfecta, hypophosphatasia, anencephaly, and encephalocele.

Because of the increased incidence of initially unexplained fractures in patients, especially those with mild or incomplete forms of osteogenesis imperfecta, the possibility of nonaccidental trauma (eg, child abuse) must be considered (130; 161; 159). Some workers have used bone mineral content to rule out abuse in mild cases of osteogenesis imperfecta (109). However, baseline information continues to be collected so such findings should be used with extreme care (136; 128). The risk of misdiagnosing child abuse must also be appreciated, perhaps especially in the very young and yet undiagnosed patient with multiple fractures (119).

Osteosarcoma has been reported in an adult with osteogenesis imperfecta, illustrating the need to differentiate (by biopsy) the hyperplastic callus formation that occurs in osteogenesis imperfecta and tumor (166).

Diagnostic workup

The diagnosis of osteogenesis imperfecta has been made traditionally by radiologic means. In 1 large study (N=76), the median number of fractures present at first diagnosis (0 to 114 months) was 3 and involved upper or lower limb and/or the spine (27). Fractures of crumpled or telescoped bones are evident, as are other pathologic bone changes.

Osteogenesis imperfecta type II in term infant (radiograph) (1)

Shortened, crumpled, and hypomineralized long bones are evident in this radiograph of the right upper arm. (Contributed by Dr. Joseph Siebert.)
Osteogenesis imperfecta type II in term infant (radiograph) (2)

Shortened, crumpled, and hypomineralized long bones are evident in this radiograph of the left leg. (Contributed by Dr. Joseph Siebert.)

Prenatal diagnosis commonly relies on ultrasound examination (65). Increased nuchal translucency (itself a nonspecific finding) and hypoechogenicity of the cranium are reported findings (39). Three-dimensional ultrasound and computed tomography have proven diagnostic as well (164; 195). Increased nuchal translucency in the first trimester has been reported in fetuses with osteogenic imperfecta (181; 80), but this finding is seen in other conditions and is not pathognomonic. Prenatal diagnosis of skeletal dysplasia by imaging is successful in approximately 66% to 89% of cases (191; 152). Three-dimensional sonography, 3-dimensional helical computer tomography (3D-HCT), and fetal MRI can confirm routine ultrasound diagnoses and can reveal additional information (105; 169). In a study, 3-dimensional techniques were more accurate than 2-dimensional ones (145). Using fetal MRI, lung volumes can be ascertained and used as a prognostic indicator (160). Other forms of skeletal dysplasia must be ruled out, of course.

Prenatal genetic workup is most commonly performed utilizing chorionic villous sampling, amniocentesis, or cordocentesis (184). Because genomic screening for the COL1A1 and COL1A2 genes is costly, others have advocated alternative approaches, such as detection of a COL1A1 null-allele (118). To date, this has been used in patients with osteogenesis imperfecta type I. Whole exome sequencing has also been used to detect mutations in COL1A1 (94). Next-generation sequencing with Sanger sequencing has been used to detect mutations in affected patients and 1 fetus (11; 115). The cost of such testing continues to fall. Genetic workup can yield surprising results; 1 Thai boy born to consanguineous parents was found to have a de novo mutation (171).

Management

Optimal management of the patient with osteogenesis imperfecta is multifaceted and includes maximizing function, minimizing deformity and disability, and maintaining comfort, independence, and socialization (84). Much of patient management has centered on orthopedic issues. Surgical techniques continue to be developed and have the potential to bring hope to patients (147). One example is the use of telescoping rods in the long bones of the leg (64). Femoral fractures and the risk of nonunion are especially prevalent in adults (70). In general, treatment modalities are effective in increasing bone density, but do not decrease the risk of fracture (90). However, it is hoped that some treatments currently under evaluation—chiefly sclerostin inhibitory antibodies and TGF beta inhibitors—may be helpful in treating bone fragility (102). Neurologists are likely to see patients with complications that develop secondary to platyspondyly, scoliosis, kyphosis, or basilar impression (53). In the latter condition, decompression and shunting can be lifesaving (56). The percutaneous injection of bone cementing compounds into areas of vertebral fracture (kyphoplasty) has been successful in relieving severe back pain that was unresponsive to other treatment (58). Bone mineral content can be established with dual-energy x-ray absorptiometry or DXA (109; 46). Bone mineral density increases in patients during childhood and appears to exhibit a degree of sexual dimorphism that is not understood (85). Hydrocephalus must be treated, of course. Endoscopic third ventriculostomy in 1 case achieved transient effectiveness, but was complicated by postoperative ischemia with subsequent brain atrophy (72). Cerebral aneurysm has been reported in rare patients with osteogenesis imperfecta (55; 78). Pathogenesis is unclear but may involve a connective tissue abnormality; as noted elsewhere in this review, other intra- and extra-cerebral vascular complications are recognized as well (86; 150).

Because of the presence of multiple fractures, pain is a constant feature of osteogenesis imperfecta. It may be acute or chronic and must be treated accordingly.

Respiratory failure may be life-threatening and may require intubation or long-term tracheotomy. However, newer approaches such as nasal bilevel positive airway pressure (n-BiPAP), may help avoid the use of invasive technologies (176). Nasal deformity may obstruct the airway and require careful surgical intervention (21).

A limited number of pharmaceutical agents have been employed in the treatment of osteoporosis, although new approaches, including gene targeting, are under investigation (31; 172). Bisphosphonates decrease bone resorption and improve bone density, promote remodeling of previous fractures, reduce the incidence of fractures and associated pain, and increase mobility in young patients (66; 71; 09). Cyclic intravenous administration of bisphosphonate has been shown to reduce pain immediately following infusion and to improve physical functioning (63). An oral form appears to be effective in school-aged children (43). However, bisphosphonates have also been reported to cause osteopetrosis in some young patients (101; 189), so this therapy requires continuing care and evaluation. Intravenous cycles of pamidronate, a member of the bisphosphonate family, have shown success in young patients in increasing lumbar bone mineral density with vertebral remodelling, lower frequency of fractures, and better attainment of motor milestones (03). Administration of bisphosphonates is often discontinued when patient growth is complete; one follow-up study suggests that this has no untoward consequences (142).

Unfortunately, the drug has also been associated with acute deterioration of respiratory function to the point of respiratory failure in some patients, and it must be closely monitored (120). A few cases have been treated successfully with bronchodilators, but others have required admission to an intensive care unit (113). Additional adverse effects of therapy include fever, muscle soreness, and gastrointestinal difficulties (139). Because of continuing uncertainties, bisphosphonates should be used in carefully controlled conditions and probably not be used in patients with mild forms of the disease (49; 137; 182).

Because of the potential for bone fracture, patients should avoid excess weight gain. Growth hormone has been used to stimulate collagen production and growth. A group of workers has suggested that growth hormone administration may increase the risk of fractures during puberty (117) by increasing bone turnover, which is already high in patients. Parathyroid hormone is still under investigation and not recommended at present (136).

Early success in pre- and postnatal transplantation of fetal mesenchymal stem cells has been reported (69). Two patients who received both pre- and postnatal infusions have shown engraftment, with no adverse reactions at 6 and 13 years of age (188). Allogeneic bone marrow and mesenchymal stromal cell transplantation have been used to produce chimeric collagen production in bone. This can result in accelerated bone growth post infusion (45; 79). Therapy using adult stem cells continues to be scrutinized (59; 174). In tissue cultures of mesenchymal stem cells derived from affected patients, mutant COL1A1 and COL1A2 genes have been inactivated using viral vectors, resulting in the production of normal type I procollagen and bone (35). Mesenchymal stem cells can be obtained from numerous sources (eg, blood, adipose tissue, bone marrow, amniotic fluid, cord blood) and differentiate into both mesodermal and nonmesodermal tissues, the former including bone; unlike embryonic stem cells, mesenchymal stem cells do not carry the risk of developing into teratomas (77; 96). At this time, workers do not anticipate using stem cell transplantation in cases of perinatal lethal disease (188).

Hearing loss is a problem for more than 50% of patients with osteogenesis imperfecta. This issue is not applicable to perinatal lethal osteogenesis imperfecta, but it is important to less severe forms. Hearing loss increases with age; it is more often conductive in young patients, sensorineural in older ones, and bilateral though not necessarily symmetric (33). Stapedotomy has proven successful in treating patients with conductive hearing loss (180). The basis for hearing loss in osteogenesis imperfecta appears to be multifactorial (76). Otosclerosis in patients involves changes in collagen molecules, notably collagen IV rather than collagen II, for reasons that are not clear (116). The prevalence of otitis media is increased in children and related to craniofacial anomalies (33). Screening for hearing deficits should occur before 5 years of age, with long-term follow-up anticipated (33).

The sclera can be fragile, leading to ocular complications such as uveal prolapse and traumatic scleral rupture (132). In 1 case, thin sclera complicated surgery to repair large and bilateral retinal tears (154). Corneas are thinner in patients than in controls (97). Treatment of basilar invagination is palliative and consists of bracing (using Minerva orthosis), transoral or transmaxillary decompression, and occipitocervical fixation (106; 114). These procedures have been reported to prevent the enlargement of associated syringomyelia (114). There is no treatment for cerebral dysgenesis in osteogenesis imperfecta.

Although intelligence is generally considered normal, the association with autism in a cohort of 7 osteogenesis imperfecta patients is a reminder to clinicians to be mindful of intellectual development (13).

Adequate nutrition is important for general health, but no foods or food supplements will provide a cure. Calcium intake is important for obvious reasons. Type I dentinogenesis imperfecta (discolored, translucent, brittle teeth) occurs in up to 40% of patients with osteogenesis imperfecta and requires special care (99; 162; 98; 173; 34; 140; 163). Other dental changes have been associated with bisphosphonate therapy (average duration at least 6 to 7 years) and include ectopic teeth, tooth impaction, and pulp obliteration (100).

The state of the dentition may dictate how food is prepared (127). Orthodontia or orthognathic surgery may be required, given the increased prevalence of malocclusion, prognathism, and other changes in craniofacial dimensions (38; 167). Pathology of the craniovertebral junction must be considered as part of orthodontic treatment (141). Unfortunately, such pathology (most commonly platybasia) may develop in spite of bisphosphonate therapy, especially when such therapy is initiated at an older age (07). A case of mandibular fracture following simple molar extraction required plate fixation (62).

Given the multi-systemic and chronic nature of the disorder, patients, and also siblings, parents, and other family members, need strong psychosocial support (134; 25). Quality of life is of obvious concern and varies with the severity of disease (47; 74). This is highlighted in a report of adult patients’ experiences with their own disease (165). Occasional families have been falsely accused of child abuse, highlighting the need for thorough workup in patients with unexplained or unexpected fractures (130; 131). A consensus statement for the rehabilitation of patients is available (112).

Outcomes

Osteonecrosis of the jaws has been related to bisphosphonate therapy (44).

Special considerations

Pregnancy

Several obstetrical and gynecologic complications have been reported in women with short stature, including those with osteogenesis imperfecta (05). Because of the rarity of patients with osteogenesis imperfecta and the still rarer possibility that these patients will be pregnant, information regarding pregnancy is limited and unsettled. Reported problems include menstrual complications, difficulties with some forms of contraception, reduced fertility, and abortion due to extreme pelvic deformity (19). Women with osteogenesis imperfecta have been reported to experience later menarche than those with other osteochondrodystrophic conditions. Affected women may also experience increased numbers of fractures with the onset of pregnancy. Cesarean delivery is recommended if an affected mother has significant kyphoscoliosis or pelvic fractures or if trauma to an affected fetus (sometimes with cephalopelvic disproportion) is to be minimized (156; 93; 111). In 1 case, Cesarean section was performed at 34 weeks to avoid cardiopulmonary compromise to the mother, a woman of short stature, wheelchair bound, and in whom fetal osteogenesis imperfecta was suspected, based on prenatal ultrasound studies (129). Of course, preterm delivery for reasons of maternal health may result in risks to the neonate (81). Thromboprophylaxis is indicated in mothers with reduced mobility (129). Affected women may experience postpartum hemorrhage secondary to uterine atony; therefore, close observation and infusion of oxytocin have been recommended (156). Because of the risk of hyperthermia during anesthesia, spinal or epidural modes of administration may be preferred. Congenital malformations, including skeletal abnormalities, have not been identified in the offspring of women treated with bisphosphonates before or during pregnancy (50). Because of the complex nature of this disorder, treating affected women during pregnancy calls for a multidisciplinary team (36).

The risk of transmission to offspring is approximately 4% to 8% in cases arising from a sporadic, de novo dominant mutation and 25% if recessive.

Anesthesia

Patients with osteogenesis imperfecta can be expected to require a significant number of procedures that require anesthesia. Individuals are especially prone to malignant hyperthermia (hyperpyrexia) during surgery. Although the origin of this reaction is unknown, it has compelled anesthesiologists to reconsider the appropriateness of certain anesthetic agents (57; 68).

The skeletal abnormalities in osteogenesis imperfecta complicate the administration of anesthesia by oronasal routes and have been the subject of several reports. Intubation and other procedures are complicated by limited opportunity for hyperextension of the neck as well as dental abnormalities, restrictive lung disease secondary to deformities of the chest, scoliosis, and the presence of basilar impression (73; 41).

In 1 review of 205 anesthetic procedures, challenges included significant blood loss (17%), difficult intravenous catheter placement (4%), difficult airway placement (1.5 %), and perioperative fracture (1%) (144). Ideally, anesthesiologists will have adequate time to prepare for the unique demands posed by this disease (42).

References

01: Alanay Y, Avaygan H, Camacho N, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 2010;86:551-9. PMID 20362275
02: Albayram S, Kizilkilic O, Yilmaz H, Tuysuz B, Kocer N, Islak C. Abnormalities in the cerebral arterial system in osteogenesis imperfecta. Am J Neuroradiol 2003;24(4):748-50. PMID 12695216
03: Alcausin MB, Briody J, Pacey V, et al. Intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta started under three years of age. Horm Res Paediatr 2013;79(6):333-40. PMID 23735642
04: Alhousseini A, Mahaseth M, Zeineddine S, et al. A non-lethal osteogenesis imperfecta type II mutation. Gynecol Obstet Invest 2019;84(2):204-8. PMID 30408804
05: Allanson JE, Hall JG. Obstetric and gynecologic problems in women with chondrodystrophies. Obstet Gynecol 1986;67:74-8. PMID 3940342
06: Andersen PE Jr, Hauge M. Osteogenesis imperfecta: a genetic, radiological, and epidemiological study. Clin Genet 1989;36:250-5. PMID 2805382
07: Arponen H, Vuorimies I, Haukka J, Valta H, Waltimo-Sirén J, Mäkitie O. Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates. J Neurosurg Pediatr 2015;15(3):313-20. PMID 25559924
08: Ashournia H, Johansen FT, Folkestad L, Diederichsen AC, Brixen K. Heart disease in patients with osteogenesis imperfecta – A systematic review. Int J Cardiol 2015;196:149-157. PMID 26100571
09: Astrom E, Soderhall S. Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta. Arch Dis Child 2002;86(5):356-64. PMID 11970931
10: Ayadi ID, Hamida EB, Rebeh RB, Chaouachi S, Marrakchi Z. Perinatal lethal type II osteogenesis imperfecta: a case report. Pan Afr Med J 2015;21:11. PMID 26401205
11: Bai Y, Kong X, Liu N, Ren S, Guo H, Zhao K. Mutational analysis and prenatal diagnosis of COL1A1 and COL1A2 genes in four Chinese families affected with osteogenesis imperfecta [Article in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017;34(5):705-8. PMID 28981938
12: Baijet B. Aspects of the history of osteogenesis imperfecta (Vrolik’s syndrome). Ann Anat 2002 184(1):1-7. PMID 11876477
13: Balasubramanian M, Jones R, Milne E, et al. Autism and heritable bone fragility: a true association? Bone Rep 2018;8:156-62. PMID 29955634
14: Baldridge D, Schwarze U, Morello R, et al. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat 2008;29(12):1435-42. PMID 18566967
15: Barkova E, Mohan U, Chitayat D, et al. Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and molecular analysis of 112 cases. Clin Genet 2015;87(4):330-7. PMID 24863959
16: Basel D, Steiner RD. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition. Genet Med 2009;11(6):375-85. PMID 19533842
17: Beighton P, Versfeld GA. On the paradoxically high relative prevalence of osteogenesis imperfecta type III in the black population of South Africa. Clin Genet 1985;27:398-401. PMID 3995789
18: Bellary SS, Steinberg A, Mirzayan N, et al. Wormian bones: a review. Clin Anat 2013;26(8):922-7. PMID 23959948
19: Benbara A, Sellier N, Benchimol M, et al. Incomplete abortion at 13 weeks’ gestation due to extreme pelvic deformity in a woman with severe osteogenesis imperfecta. J Obstet Gynaecol 2010;30:196-8. PMID 20143985
20: Bendixen KH, Gjørup H, Baad-Hansen L, et al. Temporomandibular disorders and psychosocial status in osteogenesis imperfecta - a cross-sectional study. BMC Oral Health 2018;18(1):35. PMID 29514671
21: Bilkay U, Tiftikcioglu YO, Mezili C. Management of nasal deformity in osteogenesis imperfecta. J Craniofac Surg 2010;21:1465-7. PMID 20856037
22: Blumsohn A, McAllion SJ, Paterson CR. Excess paternal age in apparently sporadic osteogenesis imperfecta. Am J Med Genet 2001;100:280-6. PMID 11343319
23: Bodian DL, Chan TF, Poon A, et al. Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships. Hum Mol Genet 2009;18(3):463-71. PMID 18996919
24: Bonita RE, Cohen IS, Berko BA. Valvular Heart Disease in Osteogenesis Imperfecta: Presentation of a Case and Review of the Literature. Echocardiography 2010;27(1):69-73. PMID 19725849
25: Bozkurt S, Baysan Arabaci L, Vara S, Ozen S, Goksen D, Darcan S. The impact of psycho-educational training on the psychosocial adjustment of caregivers of osteogenesis imperfecta patients. J Clin Res Pediatr Endocrinol 2014;6(2):84-92. PMID 24932601
26: Brizola E, Staub AL, Felix TM. Muscle strength, joint range of motion, and gait in children and adolescents with osteogenesis imperfecta. Pediatr Phys Ther 2014;26(2):245-52. PMID 24675130
27: Brizola E, Zambrano MB, Pinheiro BS, Vanz AP, Felix TM. Clinical features and pattern of fractures at the time of diagnosis of osteogenesis imperfecta in children. Rev Paul Pediatr 2017;35(2):171-7. PMID 28977334
28: Bronheim R, Khan S, Carter E, Sandhaus RA, Raggio C. Scoliosis and cardiopulmonary outcomes in osteogenesis imperfecta patients. Spine (Phila Pa 1976) 2019;44(15):1057-63. PMID 31335789
29: Bronshtein M, Weiner Z. Anencephaly in a fetus with osteogenesis imperfecta: early diagnosis by transvaginal sonography. Prenat Diagn 1992;12:831-4. PMID 1475252
30: Buyse M, Bull MJ. A syndrome of osteogenesis imperfecta, microcephaly, and cataracts. Birth Defects Orig Artic Ser 1978;14:95-8. PMID 728577
31: Byers PH. Osteogenesis imperfecta: perspectives and opportunities. Curr Opin Pediatr 2000;12:603-9. PMID 11106283
32: Byers PH, Tsipouras P, Bonadio JF, Starman BJ, Schwartz RC. Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet 1988;42(2):237-48. PMID 3341380
33: Carré F, Achard S, Rouillon I, Parodi M, Loundon N. Hearing impairment and osteogenesis imperfecta: literature review. Eur Ann Otorhinolaryngol Head Neck Dis 2019;136(5):379-83. PMID 31202667
34: Cauwels RG, De Coster PJ, Mortier GR, et al. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance. J Oral Pathol Med 2005;34(7):444-6. PMID 16011615
35: Chamberlain JR, Deyle DR, Schwarze U, et al. Gene targeting of mutant COL1A2 alleles in mesenchymal stem cells from individuals with osteogenesis imperfecta. Mol Ther 2008;16(1):187-93. PMID 17955022
36: Chamunyonga F, Masendeke KL, Mateveke B. Osteogenesis imperfecta and pregnancy: a case report. J Med Case Rep 2019;13(1):363. PMID 31822291
37: Chan TF, Poon A, Basu A, et al. Natural variation in four human collagen genes across an ethnically diverse population. Genomics 2008;91(4):307-14. PMID 18272325
38: Chang PC, Lin SY, Hsu KH. The craniofacial characteristics of osteogenesis imperfecta patients. Eur J Orthod 2007;29(3):232-7. PMID 16971690
39: Chen CP, Su YN, Chang TY, et al. Osteogenesis imperfecta type II: prenatal diagnosis and association with increased nuchal translucency and hypoechogenicity of the cranium. Taiwan J Obstet Gynecol 2012;51(2):315-8. PMID 22795121
40: Cheung MS, Arponen H, Roughley P, et al. Cranial base abnormalities in osteogenesis imperfecta: Phenotypic and genotypic determinants. J Bone Miner Res 2011;26(2):405-13. PMID 20721936
41: Chin JWE, Stuart GM. Anesthetic considerations for scoliosis surgery in a patient with recessive severe/lethal form of osteogenesis imperfecta. Paediatr Anaesth 2018;28(9):817-8. PMID 30117226
42: Cho E, Dayan SS, Marx GF. Anaesthesia in a parturient with osteogenesis imperfecta. Br J Anaesth 1992;68:422-3. PMID 1642923
43: Cho TJ, Choi IH, Chung CY, et al. Efficacy of oral alendronate in children with osteogenesis imperfecta. J Pediatr Orthop 2005;25(5):607-12. PMID 16199940
44: Christou J, Johnson AR, Hodgson TA. Bisphosphonate-related osteonecrosis of the jaws and its relevance to children -- a review. Int J Paediatr Dent 2013;23(5):330-7. PMID 23869707
45: Cole WG. Advances in osteogenesis imperfecta. Clin Orthop 2002;401:6-16. PMID 12151877
46: Crabtree NJ, Kibirige MS, Fordham JN, et al. The relationship between lean body mass and bone mineral content in paediatric health and disease. Bone 2004;35(4):965-72. PMID 15454104
47: Dahan-Oliel N, Oliel S, Tsimicalis A, Montpetit K, Rauch F, Dogba MJ. Quality of life in osteogenesis imperfecta: A mixed-methods systematic review. Am J Med Genet A 2016;170A(1):62-76. PMID 26365089
48: De Coster PJ, Cornelissen M, DePaepe A, Martens LC, Vral A. Abnormal dentin structure in two novel gene mutations [COL1A1, Arg134Cys] and [ADAMTS2, Trp795-to-ter] causing rare type I collagen disorders. Arch Oral Biol 2007;52(2):101-9. PMID 17118335
49: DiMeglio LA, Ford L, McClintock C, et al. Intravenous pamidronate treatment of children under 36 months with osteogenesis imperfecta. Bone 2004;35(5):1038-45. PMID 15542028
50: Djokanovic N, KIieger-Grossmann C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy. J Obstet Gynaecol Can 2008;30(12):1146-8. PMID 19175968
51: Dominguez LJ, Barbagallo M, Moro L. Collagen overglycosylation: a biochemical feature that may contribute to bone quality. Biochem Biophys Res Commun 2005;330(1):1-4. PMID 15781223
52: Emery SC, Karpinski NC, Hansen L, Masliah E. Abnormalities in central nervous system development in osteogenesis imperfecta type II. Pediatr Dev Pathol 1999;2:124-30. PMID 9949218
53: Engelbert RH, Gerver WJ, Breslau-Siderius LJ, et al. Spinal complications in osteogenesis imperfecta: 47 patients 1-16 years of age. Acta Orthop Scand 1998;69(3):283-6. PMID 9703404
54: Folkestad L. Mortality and morbidity in patients with osteogenesis imperfecta in Denmark. Dan Med J 2018;65(4). PMID 29619932
55: Fox A, Symons S, Aviv R. Cerebral aneurysms in a patient with osteogenesis imperfecta and exon 28 polymorphisms of COL1A2. AJNR Am J Neuroradiol 2007;28(10):1840. PMID 17898190
56: Frank E, Berger T, Tew JM Jr. Basilar impression and platybasia in osteogenesis imperfecta tarda. Surg Neurol 1982;17:116-9. PMID 7071726
57: Furderer S, Stanek A, Karbowski A, Eckardt A. Intraoperative hyperpyrexia in patients with osteogenesis imperfecta. Z Orthop Ihre Grenzgeb 2000;138:136-9. PMID 10820879
58: Furstenberg CH, Grieser T, Wiedenhofer B, Gerner HJ, Putz CM. The role of kyphoplasty in the management of osteogenesis imperfecta: risk or benefit? Eur Spine J 2010;19 Suppl 2:S144-8. PMID 19949821
59: Galamb O, Molnar B, Sipos F, Tulassay Z. Possibilities of investigation and clinical application of adult human stem cells. Orv Hetil 2003;144:2263-70. PMID 14702921
60: Galicka A. Mutations of noncollagen genes in osteogenesis imperfecta—implications of the gene products in collagen biosynthesis and pathogenesis of disease [Article in Polish]. Postepy High Med Dosw (Online) 2012;66:359-71. PMID 22706122
61: Galicka A, Wolczynski S, Anchim T, Surazynski A, Lesniewicz R, Palka J. Defects of type I procollagen metabolism correlated with decrease of prolidase activity in a case of lethal osteogenesis imperfecta. Eur J Biochem 2001;268(7):2172-8. PMID 11277941
62: Gallego L, Junquera L, Pelaz A, Costilla S. Pathological mandibular fracture after simple molar extraction in a patient with osteogenesis imperfecta treated with alendronate. Med Oral Patol Oral Cir Bucal 2010;15(6):e895-7. PMID 20526255
63: Garganta MD, Jaser SS, Lazow MA, et al. Cyclic bisphosphonate therapy reduces pain and improves physical functioning in children with osteogenesis imperfecta. BMC Musculoskelet Disord 2018;19(1):344. PMID 30249227
64: Georgescu I, Vlad C, Gavriliu T, Dan S, Pârvan AA. Surgical treatment in osteogenesis imperfecta – 10 years experience. J Med Life 2013;6(2):205-13. PMID 23904885
65: Giancotti A, Cioni M, Careri I, Longo G, Lucantoni V, Pachi A. Prenatal diagnosis of osteogenesis imperfecta. Report of a case. Minerva Ginecol 1999;51(12):505-8. PMID 10767999
66: Glorieux FH. The use of biphosphonates in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2001;14 (Suppl 6):1491-5. PMID 11837505
67: Gooijer K, Rondeel JMM, van Dijk FS, Harsevoort AGJ, Janus GJM, Franken AAM. Bleeding and bruising in osteogenesis imperfecta: International Society on Thrombosis and Haemostasis bleeding assessment tool and haemostasis laboratory assessment in 22 individuals. Br J Haematol 2019;187(4):509-17. PMID 31304589
68: Gornik-Wlaszczuk E, Majewski J, Szczygiel R, Dusiel A. Anaesthesia in children with osteogenesis imperfecta – report of 14 general anaesthetics in three children. Anaesthesiol Intensive Ther 2013;45(2):85-8. PMID 23877901
69: Gotherstrom C, Westgren M, Shaw SW, et al. Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Transl Med 2014;3(2):255-64. PMID 24342908
70: Goudriaan WA, Harsevoort GJ, van Leeuwen M, Franken AA, Janus GJM. Incidence and treatment of femur fractures in adults with osteogenesis imperfecta: an analysis of an expert clinic of 216 patients. Eur J Trauma Emerg Surg 2020;46(1):165-71. PMID 30244374
71: Guillot M, Eckart P, Desrosieres H, Amiour M, al-Jazayri Z. Osteogenesis imperfecta: a new, early therapeutic approach with biphosphonates. Arch Pediatr 2001;8:172-5. PMID 11232458
72: Hachiya Y, Hayashi M, Neqishi T, Atsumi S, Kubota M, Nishihara T. A case of osteogenesis imperfecta type II caused by a novel COL1A2 gene mutation: endoscopic third ventriculostomy to prevent hydrocephalus. Neuropediatrics 2012;43(4):225-8. PMID 22911485
73: Hajioff D, Dorward NL, Wadley JP, Crockard HA, Palmer JD. Precise cannulation of the foramen ovale in trigeminal neuralgia complicating osteogenesis imperfecta with basilar invagination: technical case report. Neurosurgery 2000;46:1005-8. PMID 10764281
74: Hald JD, Folkestad L, Harsløf T, Brixen K, Langdahl. Health-related quality of life in adults with osteogenesis imperfecta. Calcif Tissue Int 2017;101(5):473-8. PMID 28676897
75: Hansen B, Jemec GB. The mechanical properties of skin in osteogenesis imperfecta. Arch Dermatol 2002;138(7):909-11. PMID 12071818
76: Hartikka H, Kuurila K, Korkko J, et al. Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients. Hum Mutat 2004;24(2):147-54. PMID 15241796
77: Hilfiker A, Kasper C, Hass R, et al. Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation. Langenbecks Arch Surg 2011;396:489-97. PMID 21373941
78: Hirohata T, Miyawaki S, Mizutani A, et al. Subarachnoid hemorrhage secondary to a ruptured middle cerebral aneurysm in a patient with osteogenesis imperfecta: a case report. BMC Neurol 2014;14:150. PMID 25056440
79: Horwitz EM, Gordon PL, Koo WK, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 2002;99(13):8932-7. PMID 12084934
80: Hsieh CT, Yeh GP, Wu HH, Wu JL, Chou PH, Lin YM. Fetus with osteogenesis imperfecta presenting as increased nuchal translucency thickness in the first trimester. J Clin Ultrasound 2008;36(2):119-22. PMID 17764073
81: Kawakita T, Fries M, Singh J, Al-Kouatly HB. Pregnancies complicated by maternal osteogenesis imperfecta type III: a case report and review of literature. Clin Case Rep 2018;6(7):1252-7. PMID 29988651
82: Kim JW, Simmer JP. Hereditary dentin defects. J Dent Res 2007;86(5):392-9. PMID 17452557
83: Knisely AS, Frates RE, Ambler MW, Singer DB. Hydrocephalus of intrauterine onset in perinatally lethal osteogenesis imperfecta: clinical, sonographic, and pathologic correlations. Pediatr Pathol 1988;8:367-76. PMID 3062601
84: Kocher MS, Shapiro F. Osteogenesis imperfecta. J Am Acad Orthopaed Surg 1998;6:225-36. PMID 9682085
85: Kok DH, Sakkers RJ, Pruijs HE, Joosse P, Castelein RM. Bone mineral density in developing children with osteogenesis imperfecta: a longitudinal study with 9 years of follow-up. Acta Orthop 2013;84(4):431-6. PMID 23992144
86: Kolukisa M, Gökçal E, Gürsoy AE, Deniz C, Aralaasmak A, Asil T. Multiple spontaneous intracranial-extracranial arterial dissections in a patient with osteogenesis imperfecta. Case Rep Neurol Med 2017;2017:8520961. PMID 28751993
87: Kovero O, Pynnonen S, Kuurila-Svahn K, et al. Skull base abnormalities in osteogenesis imperfecta: a cephalometric evaluation of 54 patients and 108 control volunteers. J Neurosurg 2006;105:361-70. PMID 16961127
88: Kuznetsova NV, Forlino A, Cabral WA, Marini JC, Leikin S. Structure, stability and interactions of type I collagen with GLY349-CYS substitution in alpha 1(I) chain in a murine Osteogenesis Imperfecta model. Matrix Biol 2004;23(2):101-12. PMID 15246109
89: Kuznetsova NV, McBride DJ, Leikin S. Changes in thermal stability and microunfolding pattern of collage helix resulting from the loss of alpha2(I) chain in osteogenesis imperfecta murine. J Mol Biol 2003;331(1):191-200. PMID 12875845
90: Lafage-Proust MH, Courtois I. The management of osteogenesis imperfecta in adults: state of the art. Joint Bone Spine 2019;86(5):589-93. PMID 30742929
91: Lee KS, Song HR, Cho TJ, et al. Mutational spectrum of type I collagen genes in Korean patients with osteogenesis imperfecta. Hum Mutat 2006;27:599-607. PMID 16705691
92: Leng LZ, Shajari M, Hartl R. Management of acute cervical compression fractures in two patients with osteogenesis imperfecta. Spine (Phila Pa 1976) 2010;35(22):E1248-52. PMID 20881659
93: Lyra TG, Pinto VA, Ivo FA, et al. Osteogenesis imperfecta in pregnancy. Case report. Rev Bras Anestesiol 2010;60:321-4. PMID 20682164
94: Maasalu K, Nikopensius T, Kõks S, et al. Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie the severe osteogenesis imperfecta. Hum Genomics 2015;9:6. PMID 25958000
95: Macfarlane JD, Kroon HM, van der Harten JJ. Phenotypically dissimilar hypophosphatasia in two sibships. Am J Med Genet 1992;42:117-21. PMID 1308350
96: Mafi R, Hindocha S, Mafi P, et al. Sources of adult mesenchymal stem cells applicable for musculoskeletal applications--a systematic review of the literature. Open Orthop J 2011;5 Suppl 2:242-8. PMID 21886689
97: Magalhaes OA, Rohenkohl HC, de Souza LT, Schuler-Faccini L, Felix TM. Collagen I defect corneal profiles in osteogenesis imperfecta. Cornea 2018;37(12):1561-5. PMID 30272615
98: Malmgren B, Lindskog S. Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis imperfecta. Acta Odontol Scand 2003;61:72-80. PMID 12790503
99: Malmgren B, Norgren S. Dental aberrations in children and adolescents with osteogenesis imperfecta. Acta Odontol Scand 2002;60(2):65-71. PMID 12020117
100: Marçal FF, Ribeiro EM, Costa FWG, et al. Dental alterations on panoramic radiographs of patients with osteogenesis imperfecta in relation to clinical diagnosis, severity, and bisphosphonate regimen aspects: a STROBE-compliant case-control study. Oral Surg Oral Med Oral Pathol Oral Radio 2019;128(6):621-30. PMID 31399368
101: Marini JC. Do bisphosphonates make children’s bones better or brittle. N Engl J Med 2003;349:423-6. PMID 25651289
102: Marom R, Rabenhorst BM, Morello R. Osteogenesis imperfecta: an update on clinical features and therapies. Eur J Endocrinol 2020;183(4):R95-106. PMID 32621590
103: Martin E, Shapiro JR. Osteogenesis imperfecta: epidemiology and pathophysiology. Curr Osteoporos Rep 2007;5:91-7. PMID 17925189
104: McAllion SJ, Paterson CR. Causes of death in osteogenesis imperfecta. J Clin Pathol 1996;49:627-30. PMID 8881910
105: McEwing RL, Alton K, Johnson J, Scioscia AL, Pretorius DH. First-trimester diagnosis of osteogenesis imperfecta type II by three-dimensional sonography. J Ultrasound Med 2003;22:311-4. PMID 12636334
106: Menezes AH, Ryken TC, Brockmeyer DL. Abnormalities of the craniocervical junction. In: McLone DG, editor. Pediatric neurosurgery. 4th ed. Philadelphia: W.B. Saunders Co, 2001.
107: Michou L, Brown JP. Genetics of bone diseases: Paget’s disease, fibrous dysplasia, osteopetrosis, and osteogenesis imperfecta. Joint Bone Spine 2011;78:252-8. PMID 20855225
108: Moore K, Kapur RP, Siebert JR, Atkinson W, Winter T. Acalvaria and hydrocephalus: a case report and discussion of the literature. J Ultrasound Med 1999;18:783-7. PMID 10547112
109: Moore MS, Minch CM, Kruse RW, et al The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta. Am J Orthop 1998;27:797-801. PMID 9880097
110: Morello R, Bertin TK, Chen Y, et al. CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 2006;127(2):291-304. PMID 17055431
111: Morgan JA, Marcus PS. Prenatal diagnosis and management of intrauterine fracture. Obstet Gynecol Surv 2010;65:249-59. PMID 20403216
112: Mueller B, Engelbert R, Baratta-Ziska F, et al. Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta. Orphanet J Rare Dis 2018;13(1):158. PMID 30201006
113: Munns CF, Rauch F, Mier RJ, Glorieux FH. Respiratory distress with pamidronate treatment in infants with severe osteogenesis imperfecta. Bone 2004;35(1):231-4. PMID 15207762
114: Nakamura M, Yone K, Yamaura I, et al. Treatment of craniocervical spine lesion with osteogenesis imperfecta: a case report. Spine 2002;27(8):E224-7. PMID 11935123
115: Ni M, Ding H, Liu S, et al. Application of next generation sequencing for molecular diagnosis in a large family with osteogenesis imperfecta type I. Mol Med Rep 2017;16(5):6846-9. PMID 28901398
116: Niedermeyer HP, Becker ET, Arnold W. Expression of collagens in the otosclerotic bone. Adv Otorhinolaryngol 2007;65:45-9. PMID 17245021
117: Noda H, Onishi H, Saitoh K, Nakajima H. Growth hormone therapy may increase fracture risk in a pubertal patient with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2002;15(2):217-8. PMID 11874188
118: Nuytinck L, Sayli BS, Karen W, De Paepe A. Prenatal diagnosis of osteogenesis imperfecta type I by COL1A1 null-allele testing. Prenat Diag 1999;19:873-5. PMID 10521849
119: Okpechi U, Regis K, Arcia R, Soyemi K. A fracture, a family, legal entanglement, expensive investigation, and a familiar disease. Pediatric Health Med Ther 2018;9:97-100. PMID 30239531
120: Olson JA. Respiratory failure during infusion of pamidronate in a 3 year-old male with osteogenesis imperfecta: a case report. J Pediatr Rehabil Med 2014;7(2):155-8. PMID 25096867
121: Online Mendelian Inheritance in Man, OMIM. (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 166210. Online Mendelian Inheritance in Man, OMIM. Accessed October 2001.
122: Online Mendelian Inheritance in Man, OMIM. (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 166210. Online Mendelian Inheritance in Man, OMIM. Accessed October 2007.
123: Orioli IM, Castilla EE, Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genet 1986;23:328-32. PMID 3746832
124: Orioli IM, Castilla EE, Scarano G, Mastroiacovo P. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. Am J Med Genet 1995;59:209-17. PMID 8588588
125: Ortega Ade O, Rosa VL, Zwir LM, Ciamponi AL, Guimaraes AS, Alonso LG. Anatomic and dynamic aspects of stomatognathic structures in osteogenesis imperfecta: a case report. Cranio 2007;25(2):144-9. PMID 17508636
126: Osetowska E, Lewenstam K. Bilateral subcortical angiomatosis and osteogenesis imperfecta. J Neurol Sci 1967;5:79-92. PMID 6061761
127: Osteogenesis Imperfecta Foundation. Nutrition Fact Sheet. Osteogenesis Imperfecta Foundation. Accessed October 2001.
128: Pandya NK, Baldwin K, Kamath AF, Wenger DR, Hosalkar HS. Unexplained fractures: Child abuse or bone disease. A systematic review. Clin Orthop Relat Res 2011;469(3):805-12. PMID 20878560
129: Parasuraman R, Taylor MJO, Liversedge H, et al. Pregnancy management in type III maternal osteogenesis imperfecta. J Obstet Gynaecol 2007;27:619-21. PMID 17896267
130: Paterson CR, Burns J, McAllion SJ. Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. Am J Med Genet 1993;15:187-92. PMID 8456801
131: Paterson CR, McAllion SJ. Classical osteogenesis imperfecta and allegations of nonaccidental injury. Clin Orthop Relat Res 2006;452:260-4. PMID 16906116
132: Pirouzian A, O’Halloran H, Scher C, et al. Traumatic and spontaneous scleral rupture and uveal prolapse in osteogenesis imperfecta. J Pediatr Ophthalmol Strabismus 2007;44:315-8. PMID 17913179
133: Pozo JL, Crockard HA, Ransford AO. Basilar impression in osteogenesis imperfecta. A report of three cases in one family. J Bone Joint Surg Br 1984;66:233-8. PMID 6707059
134: Primorac D, Anticevic D, Barisic I, Hudetz D, Ivkovic A. Osteogenesis imperfecta--multi-systemic and life-long disease that affects whole family. Coll Antropol 2014;38(2):767-72. PMID 25145021
135: Pyott SM, Tran TT, Leistritz DF, et al. WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. Am J Hum Genet 2013;92(4):590-7. PMID 23499310
136: Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004;363(9418):1377-85. PMID 15110498
137: Rauch F, Glorieux FH. Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long. Ann Med 2005;37(4):295-302. PMID 16019729
138: Ries-Levavi L, Ish-Shalom T, Frydman M, et al. Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. Hum Mutat 2004;23(4):399-400. PMID 15024745
139: Rijks EB, Bongers BC, Vlemmix MJ, et al. Efficacy and safety of bisphosphonate therapy in children with osteogenesis imperfecta: A systematic review. Horm Res Paediatr 2015;84(1):26-42. PMID 26021524
140: Rios D, Vieira AL, Tenuta LM, et al. Osteogenesis imperfecta and dentinogenesis imperfecta: associated disorders. Quintessence Int 2005;36(9):695-701. PMID 16163872
141: Rios-Rodenas M, de Nova J, Gutierrez-Diez MP, et al. A cephalometric method to diagnosis the craniovertebral junction abnormalities in osteogenesis imperfecta patients. J Clin Exp Dent 2015;7(1):e153-8. PMID 25810828
142: Robinson ME, Trejo P, Palomo T, Glorieux FH, Rauch F. Osteogenesis imperfecta: skeletal outcomes after bisphosphonate discontinuation at final height. J Bone Miner Res 2019;34(12):2198-204. PMID 31356699
143: Rossi V, Lee B, Marom R. Osteogenesis imperfecta: advancements in genetics and treatment. Curr Opin Pediatr 2019;31(6):708-15. PMID 31693577
144: Rothschild L, Goeller JK, Voronov P, Barabanova A, Smith P. Anesthesia in children with osteogenesis imperfecta: retrospective chart review of 83 patients and 205 anesthetics over 7 years. Paediatr Anaesth 201828(11):1050-8. PMID 30295359
145: Ruano R, Molho M, Roume J, Ville Y. Prenatal diagnosis of fetal skeletal dysplasias by combining two-dimensional and three-dimensional ultrasound and intrauterine three-dimensional helical computer tomography. Ultrasound Obstet Gynecol 2004;24(2):134-40. PMID 15287049
146: Ruschel LG, Agnoletto GJ, Hunhevicz SC, Almeida DB, Arruda WO. Alternative option for osteogenesis imperfecta and trigeminal neuralgia. Rev Assoc Med Bras 2017;63(4):307-10. PMID 28614531
147: Sa-Ngasoongsong P, Saisongcroh T, Angsanuntsukh C, Woratanarat P, Mulpruek P. Using humeral nail for surgical reconstruction of femur in adolescents with osteogenesis imperfecta. World J Orthop 2017;8(9):735-40. PMID 28979858
148: Sarathchandra P, Cassella JP, Ali SY. Enzyme histochemical localisation of alkaline phosphatase activity in osteogenesis imperfecta bone and growth plate: a preliminary study. Micron 2005;36(7-8):715-20. PMID 16182549
149: Sarathchandra P, Pope FM. Unexpected ultrastructural changes in bone osteoid collagens in osteogenesis imperfecta. Micron 2005;36(7-8):696-702. PMID 16182545
150: Sardana V, Kamble S, Sharma SK, Maheshwari D, Bhushan B. Mirror aneurysm with right frontal ICH in a patient with osteogenesis imperfecta. J Assoc Physicians India 2017;65(8):103-5. PMID 28799316
151: Sayre MR, Roberge RJ, Evans TC. Nontraumatic subdural hematoma in a patient with osteogenesis imperfecta and renal failure. Am J Emerg Med 1987;5:298-301. PMID 3593495
152: Schramm T, Gloning KP, Minderer S, et al. Prenatal sonographic diagnosis of skeletal dysplasias. Ultrasound Obstet Gynecol 2009;34(2):160-70. PMID 19548204
153: Schwarze U, Cundy T, Pyott SM, et al. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Hum Mol Genet 2013;22(1):1-17. PMID 22949511
154: Scollo P, Snead MP, Richards AJ, Pollitt R, DeVile C. Bilateral giant retinal tears in osteogenesis imperfecta. BMC Med Genet 2018;19(1):8. PMID 29329516
155: Semler O, Cheung MS, Glorieux FH, Rauch F. Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genotype. Am J Med Genet A 2010;152A:1681-7. PMID 20583157
156: Sharma A, George L, Erskin K. Osteogenesis imperfecta in pregnancy: two case reports and review of the literature. Obstet Gynecol Surv 2001;56:563-6. PMID 11524621
157: Sidden CR, Filly RA, Norton ME, Kostiner DR. A case of chondrodysplasia punctata with features of osteogenesis imperfecta type II. J Ultrasound Med 2001;20:699-703. PMID 11400945
158: Sillence DO, Barlow KK, Garber AP, Hall JG, Rimoin DL. Osteogenesis imperfecta, type II. Delineation of the phenotype with reference to genetic heterogeneity. Am J Med Genet 1984;17:407-23. PMID 6702894
159: Singh Kocher M, Dichtel L. Osteogenesis imperfecta misdiagnosed as child abuse. J Pediatr Orthop B 2011;20:440-3. PMID 21716141
160: Solopova A, Wisser J, Huisman TA. Osteogenesis Imperfecta Type II: Fetal Magnetic Resonance Imaging Findings. Fetal Diagn Ther 2008;24(4):361-367. PMID 18931501
161: Steiner RD, Pepin M, Byers PH. Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta. J Pediatr 1996;128(4):542-7. PMID 8618190
162: Stephen LX, Beighton P. Dental management of severe dentinogenesis imperfecta in a mild form of osteogenesis imperfecta. J Clin Pediatr Dent 2002;26(2):131-6. PMID 11878277
163: Subramaniam P, Mathew S, Sugnani SN. Dentinogenesis imperfecta: A case report. J Indian Soc Pedod Prev Dent 2008;26(2):85-7. PMID 18603736
164: Suzumori N, Hasegawa T, Sugiura-Ogasawara M. Prenatal diagnosis of osteogenesis imperfecta type II by three-dimensional ultrasound and computed tomography. J Obstet Gynaecol Res 2011;37(6):664-5. PMID 21450031
165: Swezey T, Reeve BB, Hart TS, et al. Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community. Osteoporos Int 2019;30(2):507-11. PMID 30191258
166: Takahashi S, Okada K, Nagasawa H, Shimada Y, Sakamoto H, Itoi E. Osteosarcoma occurring in osteogenesis imperfecta. Virchows Arch 2004;444(5):454-8. PMID 15214333
167: Tashima H, Wattanawong K, Ho CT, et al. Orthognathic surgery considerations for patients with undiagnosed type I osteogenesis imperfecta. J Oral Maxillofac Surg 2011;69:2233-41. PMID 21398007
168: Tauer JT, Robinson ME, Rauch F. Osteogenesis imperfecta: new perspectives from clinical and translational research. JBMR Plus 2019;3(8):e10174. PMID 31485550
169: Teng SW, Guo WY, Sheu MH, Wang PH. Initial experience using magnetic resonance imaging in prenatal diagnosis of osteogenesis imperfecta type II: a case report. Clin Imaging 2003;27(1):55-8. PMID 12504324
170: Thompson EM, Young ID, Hall CM, Pembrey ME. Recurrence risks and prognosis in severe sporadic osteogenesis imperfecta. J Med Genet 1987;24:390-405. PMID 3612715
171: Tongkobpetch S, Limpaphayom N, Sangsin A, Suphapeetiporn K, Shotelersuk V. A novel de novo COL1A1 mutation in a Thai boy with osteogenesis imperfecta born to consanguineous parents. Genet Mol Biol 2017;40(4):763-7. PMID 28956891
172: Tournis S, Dede AD. Osteogenesis imperfecta - a clinical update. Metabolism 2018;80:27-37. PMID 28625337
173: Tsai CL, Lin YT, Lin YT. Dentinogenesis imperfecta associated with osteogenesis imperfecta: report of two cases. Chang Gung Med J 2003;26(2):138-43. PMID 12718392
174: Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S. Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin Proc 2009;84(10):893-902. PMID 19797778
175: van Dijk FS, Pals G, Van Rijn RR, et al. Classification of osteogenesis imperfecta revisited. Eur J Med Genet 2010;53:1-5. PMID 19878741
176: Vega-Briceno L, Contreras I, Sanchez I, Bertrand P. Early use of BiPAP in the management of respiratory failure in an infant with osteogenesis imperfecta: case report. Rev Med Chil 2004;132:861-4. PMID 15379335
177: Venturi G, Tedeschi E, Mottes M, et al. Osteogenesis imperfecta: clinical, biochemical and molecular findings. Clin Genet 2006;70:131-9. PMID 16879195
178: Verkh Z, Russell M, Miller CA. Osteogenesis imperfecta type II: microvascular changes in the CNS. Clin Neuropathol 1995;14:154-8. PMID 7671457
179: Viljoen D, Beighton P. Osteogenesis imperfecta type III: an ancient mutation in Africa. Am J Med Genet 1987;27:907-12. PMID 3425600
180: Vincent R, Wegner I, Stegeman I, Grolman W. Stapedotomy in osteogenesis imperfecta: a prospective study of 32 consecutive cases. Otol Neurotol 2014;35(10):1785-9. PMID 24751750
181: Viora E, Sciarrone A, Bastonero S, et al. Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Am J Med Genet 2002;109(4):336-7. PMID 11992492
182: Vyskocil V, Pikner R, Kutilek S. Effect of alendronate therapy in children with osteogenesis imperfecta. Joint Bone Spine 2005;72:416-23. PMID 16214075
183: Wainwright H, Beighton P. Osteogenesis imperfecta and holoprosencephaly. Clin Dysmorphol 2007;16(3):189-91. PMID 17551335
184: Wang W, Wu Q, Cao L, Sun L, Xu Y, Guo Q. Mutation analysis of COL1A1 and COL1A2 in fetuses with osteogenesis imperfecta type II/III. Gynecol Obstet Invest 2020;85(2):149-52. PMID 25633413
185: Ward LM, Lalic L, Roughley PJ, Glorieux FH. Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV. Hum Mutat 2001;17(5):434. PMID 11317364
186: Weissman A, Diukman R, Auslender R. Fetal acrania: five new cases and review of the literature. J Clin Ultrasound 1997;25:511-4. PMID 9350573
187: Wekre LL, Kjensli A, Aasand K, Falch JA, Eriksen EF. Spinal deformities and lung function in adults with osteogenesis imperfecta. Clin Respir J 2014;8(4):437-43. PMID 24308436
188: Westgren M, Gotherstrom C. Stem cell transplantation before birth – a realistic option for treatment of osteogenesis imperfecta? Prenat Diagn 2015;35(9):827-32. PMID 25962526
189: Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonate-induced osteopetrosis. N Engl J Med 2003;349:457-8. PMID 12890844
190: Witecka J, Auguściak-Duma AM, Kruczek A, et al. Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix. J Appl Genet 2008;49(3):283-95. PMID 18670065
191: Witters I, Moerman P, Fryns JP. Skeletal dysplasias: 38 prenatal cases. Genet Couns 2008;19(3):267-75. PMID 18990981
192: Wladimiroff JW, Niermeijer MF, Van der Harten JJ, et al. Early prenatal diagnosis of congenital hypophosphatasia: case report. Prenat Diagn 1985;5(1):47-52. PMID 3883342
193: Xia XY, Cui YX, Huang YF, et al. A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family. Clin Chim Acta 2008;398(1-2):148-51. PMID 18755172
194: Zankl A, Mornet E, Wong S. Specific ultrasonographic features of perinatal lethal hypophosphatasia. Am J Med Genet A 2008;146A(9):1200-4. PMID 18386808
195: Zou DH, Shao Y, Zhang JH, et al. Determination of a newborn with lethal type II osteogenesis imperfecta and other anomalies using autopsy and postmortem MSCT--a case report. Fa Yi Xue Za Zhi 2016;32(1):69-73. PMID 27295861

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Osteogenesis imperfecta type II: cerebral dysgenesis

Associated Disorders

Osteogenesis imperfecta type I
Osteogenesis imperfecta type II
Osteogenesis imperfecta type III
Osteogenesis imperfecta type IV
Osteogenesis imperfecta type V
- Osteogenesis imperfecta type VI
- Osteogenesis imperfecta type VII
- Osteogenesis imperfecta type VIII

Differential Diagnosis

hypophosphatasia
chondrodysplasia punctata
infantile copper deficiency
hypomineralization of the calvaria
acrania
- nonaccidental trauma
- child abuse
- osteosarcoma

Also Relevant

Anencephaly
Basilar impression
Intellectual disability
Megalencephaly

Content Categories

Developmental Malformations

Web References

Clinical Trials

NIH: Osteogenesis Imperfecta

Osteogenesis imperfecta type II: cerebral dysgenesis

Osteogenesis imperfecta type II: cerebral dysgenesis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Walker-Warburg syndrome

Congenital muscular dystrophy: merosin deficient form

Ependymal and choroid plexus cysts

Core myopathies

Von Hippel-Lindau disease

Pontocerebellar hypoplasia

Incontinentia pigmenti

Hemimegalencephaly

Osteogenesis imperfecta type II: cerebral dysgenesis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Walker-Warburg syndrome

Congenital muscular dystrophy: merosin deficient form

Ependymal and choroid plexus cysts

Core myopathies

Von Hippel-Lindau disease

Pontocerebellar hypoplasia

Incontinentia pigmenti

Hemimegalencephaly

This is an article preview.
Start a Free Account
to access the full version.