Osteogenesis imperfecta

Learning objectives.

By reading this article, you should be able to:

• •Recall the epidemiology and classification of osteogenesis imperfecta.
• •Identify the common clinical presentations.
• •Describe the common types of surgical procedures that these children undergo.
• •Discuss the important considerations for the anaesthetist before, during and after surgery.

Key points.

• •Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen with multiple causative gene variants, leading to multiple phenotypic subtypes, associated with bone fragility and fractures.
• •Perioperative management of OI should involve a careful multidisciplinary approach.
• •Preoperative planning should include formulation of a plan for managing the airway plan and appropriate preoperative investigations.
• •Non-invasive blood pressure cuffs should be positioned carefully, but in some patients an intra-arterial catheter is needed.
• •Regional anaesthesia should be considered on a case-by-case basis, as there is no high-quality evidence to guide practice.

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare genetic multisystem disorder of Type I collagen associated with bone fragility, fractures and connective tissue abnormalities, with highly heterogeneous phenotypic features and varying genetic basis. It has an incidence of one in 15–20,000 births.¹ Greater incidence is within populations with a higher level of consanguinity or number of carriers.²

Classification

The original Sillence classification identified four types of OI in 1979 (Types I–IV), based upon clinical features and genetic inheritance.³ Further work led to the identification of variants in COL1A1 and COL1A2 genes and the identification of abnormalities within the α1 and α2 chains of Type 1 collagen, the most abundant protein of bone, skin and tendon. Variants in these genes cause 85–90% of OI cases.^1,4 Multiple rarer genetic variants within other collagen-related genes, with varying inheritance patterns, have been since identified, with the current Online Mendelian Inheritance in Man (OMIM) database listing up to Type XXII.

Attempts at classification of the whole spectrum of OI have been debated, with no overall agreement, based on clinical or genetic criteria. In the clinical classification, described by Van Dijk and Sillence, OI is segregated into (i) non-deforming OI with blue sclerae, (ii) perinatally lethal OI, (iii) progressive deforming OI, (iv) common variable OI with normal sclerae and (v) OI with calcification in interosseous membranes.⁴ Other phenotypes exist, such as Bruck syndrome, a severe OI phenotype associated with joint contractures. Classification based on clinical findings allows for treatment decisions to be made on clinical grounds but leads to genetic heterogeneity within the groups. Conversely, a genetics-based classification allows for clear delineation of the culprit gene variant with an inheritance pattern for genetic counselling and research but is progressively lengthening as more culprit variants are discovered.⁵

Online Mendelian Inheritance in Man uses a mixed approach, where the four Sillence types are listed as Types I–IV, with the remainder by type number and gene variant. In addition, grouping by functional metabolic consequence of these gene variants has been proposed by Forlino and Marini and colleagues.^1,2 These groups are listed as follows, categorised by pathophysiology:

• (i)Defects in collagen synthesis, structure or processing
• (ii)Defects in collagen modification
• (iii)Defects in collagen folding and cross-linking
• (iv)Defects in bone mineralisation
• (v)Defects in osteoblast development

Table 1 shows the current OI subtypes as listed on OMIM.

Table 1.

Classification of OI by functional metabolic defects and genetic variants, with data compiled from Forlino and Marini, Marini and colleagues, Marom and colleagues and the OMIM database (www.omim.org).^1,2,6 Reprinted by permission from Springer Nature.² AD, autosomal dominant; AR, autosomal recessive; XL, X-linked.

Gene	Type	Inheritance
Defects in collagen synthesis, structure or processing
COL1A1/2	I–IV	AD
BMP1	XIII	AR
Defects in bone mineralisation
IFITM5	V	AD
SERPINF1	VI	AR
Defects in collagen modification
CRTAP	VII	AR
LEPRE1/P3H1	VIII	AR
PPIB	IX	AR
TMEM38B	XIV	AR
Defects in collagen folding and cross-linking
SERPINH1	X	AR
FKBP10	XI	AR
PLOD2	No type	AR
Defects in osteoblast development with collagen insufficiency
SP7	XII	AR
WNT1	XV	AR
CREB3L1	XVI	AR
SPARC	XVII	AR
MBTPS2	XIX	XL
The following have been described recently and are currently unclassified by mechanism
TENT5A7	XVIII	AR
MESD8	XX	AR
KDELR29	XXI	AR
CCDC13410	XXII	AR

Diagnosis and screening

Osteogenesis imperfecta remains a clinical diagnosis and depends on the presentation, such as fracture(s) or a family history; examination and radiographs of the long bones, spine and skull together with an evaluation of dentition; and the presence of other associated features. Genetic testing can be used to confirm a clinical diagnosis. Timing of diagnosis usually ranges anywhere from prenatally to early childhood, although some diagnoses occur later in milder forms. Unexpected fractures in infants and young children may lead to further assessment for OI, possibly triggered by an initial diagnosis of non-accidental injury. Rapid diagnoses can be facilitated by genetic sequencing using panels of all known genes associated with OI, although genetic sequencing may still require several weeks even if performed urgently, and about 6 months is usual in the UK.^1,2

Antenatal screening for OI is mostly limited to prenatal ultrasound, which can detect the perinatally lethal forms of OI (Type II) by 14–16 weeks of gestation. Progressive deforming OI (Type III) may be identified by approximately 18 weeks of gestation when longitudinal growth decreases towards the fifth percentile, although it should be noted that there may be overlap in clinical features between Types II and III. Where unexpected skeletal abnormalities have been detected, targeted trio (parents and fetus) rapid exome (the protein-coding regions of the genome) sequencing with expert multidisciplinary review (for case selection and data interpretation) may allow timely diagnoses that would aid parental counselling and pregnancy management.¹¹ In individuals with a family history of OI, chorionic villus samples may be sequenced, and in certain specific scenarios, non-invasive prenatal diagnosis (based on cell-free fetal DNA in maternal blood) may have a role.¹² In families where a parent has a dominantly inherited form of OI, both parents are recessive carriers, or where parental mosaicism for a dominant form has been identified (usually from parental testing after the identification of an affected offspring), embryos resulting from in vitro fertilisation can be screened.²

Clinical features

As a heterogeneous group of disorders, manifestations in individual patients vary in both features and severity. Several other features may be present, dependent on the underlying genetic variant, although an exhaustive list of the clinical features attributed to each genetic variant would be beyond the scope of this article.

The primary manifestations of OI are bone fragility, deformation and osteoporosis, with biochemical markers of increased bone turnover. Other features may include^2,4,13,14

• (i)Airway: dentinogenesis imperfecta (DI), malocclusion and atlantoaxial instability¹⁵
• (ii)Pulmonary: pulmonary function impairment (restrictive defect)
• (iii)Cardiovascular: cardiac valvular abnormalities (mitral regurgitation/prolapse), atrial and ventricular septal defects and aortic root dilatation
• (iv)Nervous system: blue sclerae, young adult-onset conductive or sensory hearing loss, craniocervical junction abnormalities (e.g. basilar impression/invagination, which may lead to foramen magnum narrowing and hydrocephalus, and potential neurological compromise caused by distortion of brain anatomy)
• (v)Spinal: kyphoscoliosis and spondylolisthesis
• (vi)Other musculoskeletal: chest wall deformities, muscle weakness and ligamentous laxity

Table 2 summarises the typical features of the main types of OI listed in the clinical classification.

Table 2.

Typical features of the five subtypes of OI described by the clinical classification, including Bruck syndrome.⁴

Clinical classification	Typical features
Non-deforming OI with blue sclerae (Type I)	•Most common in European communities; frequently mild but variable expression in families •Increased bone fragility, usually with osteoporosis •Blue–grey sclerae •Susceptible to conductive and sensorineural hearing loss; vertigo •Long bones/spine deformities uncommon; scoliosis usually idiopathic if it occurs •Likely more severe if DI is also present (higher likelihood of fractures at birth, more severe short stature and more skeletal deformities)
Common variable OI (Type IV)	•Variable severity within families •Recurrent fractures; variable degrees of deformity of long bones and spine; osteoporosis •Normal sclerae: blue at birth but fade during childhood •Increased prevalence of posterior fossa compression syndromes attributable to basilar impression (30% patients; 16% symptomatic)
Progressively deforming OI (Type III)	•Usually presents as newborn or infant: born at or near term, with normal weight •Fragility of bone and multiple fractures lead to progressive deformity of skeleton and poor longitudinal growth (<3rd centile in height for age and sex) •May develop ‘popcorn’ radiological appearance in metaphyses during childhood; thin, osteopaenic ribs with crowding may occur with increasing platyspondyly; skull shows Wormian bones •Sclerae may be blue at birth but fade with age •Progressive kyphoscoliosis, leading to early mortality in past by second decade; pulmonary hypertension; and cardiorespiratory failure; bisphosphonate therapy now allows survival into adulthood •Other features: hearing loss in some adults; DI may be present
Perinatally lethal OI (Type II)	•Extremely severe features: fetuses at 18–20 weeks of gestation have crumpled, bowing or angulation deformities of long bones; deficiencies of ossification of facial and skull bones; rib fractures •Neuropathologies described in a few cases: brain neuronal migration defects or white matter changes •In developed countries, prenatal diagnosis by ultrasound and DNA analysis often leads to termination of pregnancy •20% stillborn; 90% die by 4 weeks of age •Some babies with less severe phenotype (fewer rib fractures; some overlap with Type III) may survive and can be treated with bisphosphonates •Probably in constant pain: excess perspiration, pallor, anxiety at being touched and moving their limbs very little because of multiple fractures
OI with calcification in interosseous membranes (Type V)	•Accounts for ∼5% of hospital patients in clinical studies •Calcification of forearm interosseous membranes seen early in life; leads to difficulties in supination and pronation, and eventual dislocation of radial heads •Absence of blue sclerae and DI; may have no Wormian bones or an abnormal Wormian pattern •Characteristic bone histomorphometry with coarse mesh-like lamellation •Higher alkaline phosphatase values •Increased risk of the development of hyperplastic calluses from fracture or orthopaedic surgery: a massive callus with swelling and pain at site of a fracture, even minor ones—an emergency!
Bruck syndrome	•Usually, a severe OI presentation with congenital joint contractures •Inheritance pattern AR •Two subtypes, Bruck syndrome types 1 and 2, caused by gene variants in FKBP10 and PLOD2, respectively •Grey–white sclerae •Skull: abnormal Wormian bone pattern •Small stature •Early and frequent fractures •Kyphoscoliosis; predisposition to abnormal cervical spine anatomy

General management

There is currently no cure for OI. A multidisciplinary approach is needed to care for these patients, involving various specialties, including paediatric medical, surgical and allied health professionals. Each patient is unique and usually has an individualised treatment plan based upon the clinical presentation, dependent on type and severity. Management is supportive and includes rehabilitation, medical/pharmacological and surgical strategies. Rehabilitation focuses on patient mobility, joint and muscle strengthening, protective handling and positioning by carers to avoid injuries and environmental and lifestyle adaptations to promote participation and independence.² Bisphosphonates are an important part of management, and other therapies, such as monoclonal antibodies and stem cell therapy, are currently undergoing trials.⁶ Presently, one Phase I stem cell therapy trial is being conducted in paediatric patients.¹⁶ These therapies are usually combined with surgical management.

Perioperative management

Types of surgical procedures

The vast majority of surgeries undertaken in children with OI are orthopaedic, either acutely for fractures or as part of the elective management of their disease.^14,17, 18, 19, 20, 21 Lower limb procedures include osteotomies with intramedullary rods, aiming for stability and alignment. Stand-alone plates and screws are avoided to prevent stress-risers leading to fractures proximal or distal to the plate.¹⁴ These procedures may be performed ‘open’ or percutaneously depending on the severity of deformity and bone shape.² Upper limb surgery includes placement of humeral and forearm rods, and it aims to address functional limitations. This procedure is especially important in patients who are often reliant on wheelchairs for mobility and on their upper limbs for self-care and independence. Other procedures include those addressing joint and spinal deformities. Scoliosis may be treated with spinal fusion once certain Cobb angle thresholds are met; one centre recommends that it be considered once curves reach 45˚, with our institution (Great Ormond Street Hospital for Children [GOSH]) making similar recommendations alongside full multidisciplinary assessment. Rarely, surgery may be required for craniocervical junction abnormalities, specifically basilar invagination with clinical symptoms. These symptoms may include headaches (especially strain-induced, such as by coughing or sneezing); neck pain; tinnitus; visual disturbances; dysphagia; and symptoms and signs of myelopathy, such as sensory symptoms, limb weakness, long tract signs and sleep-disordered breathing. Treatment of hydrocephalus in patients with basilar invagination should be prioritised before other interventions.¹⁴

Patients often undergo multiple procedures. Ross and colleagues, in their US-based single-centre retrospective study, found that 273 procedures were performed in 49 patients over a 20 yr period.²⁰ Of these procedures, 229 (83.8%) were orthopaedic, at a median age of 7.9 yrs. Of the 44 non-orthopaedic procedures, the specialties involved were general surgery, dentistry or oral surgery, urology, neurosurgery and obstetrics and gynaecology.²⁰ Within orthopaedics, the types of procedures undertaken were illustrated by Liang and colleagues, who retrospectively studied 252 orthopaedic procedures in 132 paediatric patients in a Chinese centre between 2015 and 2019.²¹ Of these procedures, osteotomies were the most frequently performed (80.1%), some of which included three or four bones (5.9% and 2.4%, respectively). Other procedures ranged from fracture handling, debridement, plaster manipulation and removal of fixation materials.²¹

Preoperative management and investigations

Patients with a range of OI types present for anaesthesia; Types I, III and IV are most frequently reported, varying between centres and patients' characteristics, with a range of disease severity.18, 19, 20, 21

A thorough anaesthetic history from the child (where applicable) and the parents, examination and close communication with the child's multidisciplinary team will provide good insight into the patient's status and previous medical and surgical history. Assessment of the airway is vital to prepare for potential difficulties, which may arise from facial dysmorphism, macroglossia, a short neck and the concurrent presence of dentinogenesis imperfecta.^13,22

Assessment of the neck is important because of the possibility of cervical spine instability or movement limitations arising from thoracic kyphoscoliosis or other skeletal abnormality. Atlantoaxial instability is very rare in patients with OI but should be considered. Whilst patients may present with a clearer history (neck trauma, pain and reduced range of movement), the neurological signs and symptoms arising from cervical spine pathology are often much more subtle, especially in children. Many OI centres routinely screen for spine and craniocervical abnormalities through clinical assessment, plain lateral skull and cervical spine radiographs and CT or MRI for basilar invagination if required. Nevertheless, detection of any concerns should be referred to the multidisciplinary team for further assessment before proceeding.¹⁵

Basic investigations, such as a full blood count and a group and save, are helpful because of the potential for bleeding diatheses in children with OI, for which the mechanism remains elusive.^2,23,24 Opinion seems divided as to whether one should perform preoperative coagulation studies, as the results tend to be normal.^23,24 One centre reports that they do not routinely perform coagulation workup, whilst another reference suggests that platelet counts and standard coagulation tests be performed along with platelet function tests and Factor VIII activity if a past medical history of haemorrhagic diathesis is present.^13,22 At GOSH, we usually perform routine preoperative coagulation studies.

Other investigations that may be considered include spirometry, as spirometry may show a restrictive defect from kyphoscoliosis or other thoracic abnormalities. Spirometry may be complemented by preoperative blood gas analysis, which may show carbon dioxide retention and hypoxaemia, and this would have an impact on postoperative care planning. Cardiac evaluation (electrocardiogram and echocardiogram) is advisable if there is a history of cardiac abnormalities (including parental history of OI and associated cardiac abnormalities) or abnormal findings on clinical examination.^13,22

A detailed perioperative plan must be formulated using a multidisciplinary approach, detailing the need for further investigations, imaging or optimisation; a plan for airway management; considerations for postoperative analgesia requirements; and an appropriate location for postoperative care. A discussion of risks and benefits should be undertaken with the child (depending on their age) and their parents/carers, including the need for premedication. Vascular access may be difficult and should be discussed and considered at an early stage.

Intraoperative management

Airway management

Tracheal intubation appeared to be the airway management strategy of choice in the studies by Liang and colleagues, and it was performed in 94.4% of their 252 patients with no airway-related complications reported.²¹ Rothschild and colleagues, who retrospectively reviewed the charts of 83 children undergoing 205 anaesthetics in a US centre, reported difficulties in airway management in 1.5% of patients.¹⁸ In contrast, Mohmmad and colleagues reported use of supraglottic airway device (SAD) in 91.9% of 93 patients in their South African cohort, stating that their use may prevent airway injury in patients with OI. They reported encountering airway difficulties in 3.22% of their patients.¹⁹ Use of indirect laryngoscopy (video) was widespread in the study by Liang and colleagues.²¹ It should be considered, especially in the light of Pediatric Difficult Intubation Registry findings.²⁵ Oropharyngeal airways, SADs and fibreoptic scopes remain important tools, and they should be readily available with other difficult airway equipment.

Our own experience at GOSH is closer to that of Liang and colleagues.²¹ However, practice was varied. Just under three quarters of our patients' airways were managed by tracheal intubation, with most of our patients managed with direct laryngoscopy, and approximately one-tenth required use of videolaryngoscopy. We suggest that surgical positioning, duration of surgery and patient-specific factors be considered before deciding on the strategy for airway management, along with appropriate contingency plans, equipment and personnel in place before induction of anaesthesia.

The need for careful airway management in children with craniocervical junction abnormalities must be emphasised. Preoperative multidisciplinary discussion and planning are essential to prevent excessive manipulation of the neck and their related complications. This procedure may be achieved by manual in-line stabilisation of the cervical spine with an assistant, along with adaptations to laryngoscopic technique, such as by using indirect techniques.¹³

Traditional teaching advises avoiding suxamethonium because of concerns regarding acute hyperkalaemic response and contraction-induced fractures.²² The ready availability of non-depolarising neuromuscular blocking agents allows these risks to be bypassed entirely. The presence of dentinogenesis imperfecta may mean that teeth are susceptible to damage and loss.

Monitoring and positioning

The Association of Anaesthetists' monitoring standards must be adhered to as far as it is feasible, although suitable adaptations may have to be considered.²⁶ Fragility of skin and bone means that care in handling, padding and positioning needs to be undertaken with meticulous care, as fractures have been reported perioperatively and during patient positioning. The presence of the surgical team during positioning is highly advisable.^13,18,27

Haemodynamic monitoring

Two studies have looked specifically at the use of non-invasive blood pressure (NIBP) cuffs perioperatively in patients with OI because of concern that they may cause iatrogenic fractures.^20,27 Sullivan and colleagues retrospectively reviewed the records of 96 orthopaedic and two non-orthopaedic procedures in 37 patients in a US centre, and they found that 81 (82.7%) were monitored using NIBP cuffs.²⁷ Ross and colleagues looked at 273 procedures, of which 246 (90.1%) used NIBP cuffs and 16 (5.9%) used both an invasive arterial line and an NIBP cuff.²⁰ Both studies included OI Types I, III and IV, and neither of these studies reported intraoperative fractures attributable to using an NIBP cuff. Together, they reported two fractures. One was associated with the procedure itself.²⁰ The other occurred during positioning.²⁷ Rothschild and colleagues reported two perioperative fractures, but their study did not include the rate of NIBP cuff use, and they were unable to attribute an aetiology to these fractures.¹⁸ Unfortunately, the sites of cuff placement were also not recorded in these two latter cases, making it difficult to categorically rule out the NIBP cuff as a culprit. Our own experience reflects the evidence presented here, with no fractures associated with the use of NIBP cuffs. Goeller and colleagues previously made some recommendations on NIBP cuff use.¹³ They suggested not starting NIBP measurement until the child is anaesthetised; placement of an appropriately sized cuff on a previously rodded extremity or one with a large, long bone (e.g. humerus or femur); using lower peak inflation pressures; reducing the time before aborting a BP measurement; and a reduced frequency of BP measurement to every 10 min as the clinical situation allows.¹³

Invasive blood pressure monitoring has been advocated by some authors in preference to NIBP monitoring because of the risk of causing iatrogenic fractures.²² However, invasive arterial monitoring presents its own risks.²⁷ Ross and colleagues, Liang and colleagues and Sullivan and colleagues reported use of invasive monitoring in 20.6%, 71.8% and 17.3% of their patients, respectively, with no reports of complications from their placement.^20,21,27 Taken together and taking into account the lack of larger prospective data sets, the collated experience seems to suggest that NIBP cuffs may be suitable for use with appropriate precautions, reserving invasive arterial monitoring for children with the most severe forms of OI, where there is no appropriate placement site, where the surgery may be prolonged or where large blood loss volumes are anticipated.¹³

Surgical tourniquets

Neither the studies by Ross and colleagues nor Sullivan and colleagues reported any fractures from surgical tourniquet use.^20,27 Sullivan and colleagues reported use of surgical tourniquets on proximal femurs at 250 mmHg, although the number of operations where tourniquets were used was small at 30 (31.3%) of the 96 orthopaedic procedures.²⁷ Similarly, Ross and colleagues reported tourniquet use in 61 (22.3%) procedures, in which 80 tourniquets were utilised across both upper (16.3%) and lower (83.8%) extremities, with the range of inflation pressures between 180 and 300 mmHg, across patients with OI Types I (31.8%), III (11.1%) and IV (25.9%).²⁰ Rothschild and colleagues and Liang and colleagues both reported surgical tourniquet use, but they reported no associated iatrogenic fractures.^18,21 Given the lack of larger data sets, it would be impossible to conclude that surgical tourniquets are safe to use in patients with OI, although the present, limited data suggest that they may be considered with appropriate precautions. Our institution's preference is to avoid using surgical tourniquets as much as possible in children with osteogenesis perfecta. The use of a surgical tourniquet might be considered in limited scenarios, where children have very mild treated disease, who have not had any recent fractures and with ongoing surgical bleeding, using an inflation pressure at 100 mmHg above systolic blood pressure.

Temperature

Although patients with OI may be prone to developing high temperatures whilst undergoing general anaesthesia, this case is not believed to be malignant, and there is no evidence for treating pyrexias with dantrolene.^13,17,19,28 Liang and colleagues showed in their study that hyperthermia (>37.5˚C) and fever (>38.5˚C) occurred in 24.2% and 2.8% of their patients, respectively.²¹ Temperature monitoring and control are therefore important aspects of perioperative management, generally through supportive measures, such as using forced air warmers set to an appropriate temperature.

Blood loss and transfusion

Rothschild and colleagues showed that in 17% of their patients, blood loss exceeded 10% of estimated blood volume; patients with OI Type III (severe) were more likely to have significant blood loss compared with those of OI Type I (mild).¹⁸ Duration of surgery also contributed significantly to a predicted blood loss >10% of estimated blood volume.¹⁸ Liang and colleagues reported transfusion rates of 25.4%, with 18.3% of patients reported to be complicated by massive blood loss, which they defined as >20% of total estimated blood volume.²¹ As with the data of Rothschild and colleagues, their regression analysis showed significant associations between blood loss with surgical duration.¹⁸ Furthermore, in their study consisting mostly of limb osteotomies, they found an association between significant blood loss and the number of bone segments being operated on. Interestingly, they did not find an association between blood loss and with OI type.²¹ Tranexamic acid and maintaining normothermia may be beneficial in addition to other standard measures to prevent blood loss. Where massive blood loss may be anticipated (e.g. long procedure and multiple bone segments), it may be prudent to use a cell saver device.

Postoperative care, pain management and the use of regional anaesthesia

A multimodal approach to analgesia should be used, including simple analgesia and opioids, with consideration of other adjuncts as appropriate. These adjuncts include patient- or nurse-controlled analgesia and regional anaesthesia.

The use of regional anaesthesia techniques, including epidural, combined spinal–epidural and caudal analgesia and peripheral nerve blocks, has been described by several centres, with no reports of serious complications.^13,18,21 The reported incidence of difficult or failed neuraxial block ranged from 2.6% to 12.5%.^18,19,21 Beethe and colleagues performed a wide-ranging narrative review of neuraxial and regional anaesthesia use in adult and paediatric patients with OI, and they found a similar lack of serious complications.²⁹ However, considering that most of the available evidence comprised case reports and small non-randomised studies, these authors highlighted the lack of sufficient evidence to ‘validate or refute the potential risks associated with the use regional and neuraxial techniques in patients with OI’.

In a set of perioperative best practice guidelines for patients with skeletal dysplasias, White and colleagues included the statement, ‘Anecdotal reports suggest that epidural anesthesia be used with caution in children with skeletal dysplasia due to risk of neurological injury’, as it achieved the required 80% consensus threshold through a modified Delphi method.³⁰ This statement arose through reports of paraplegia occurring in two patients, where epidural anaesthesia was used for bilateral lower limb surgery. The patients had backgrounds of Morquio A with spinal stenosis and mucopolysaccharidosis Types I–H with an 80˚ cervicothoracic kyphosis, respectively.^31,32 Taking this into perspective, Beethe and colleagues noted that, although OI is a subtype of skeletal dysplasia, the clinical manifestation of OI is significantly different to mucopolysaccharidoses, and that they rarely exhibit spinal stenoses.²⁹ They went on to state that their ‘narrative review did not find reports of spinal stenosis nor paralysis or sensory deficits in the patients with OI who received neuraxial anesthesia’.²⁹

The use of regional or neuraxial anaesthesia should therefore be considered on an individual patient basis. The benefits of regional anaesthesia include reduced need for perioperative opioids and a potential to mitigate the risk of chronic pain and anxiety in a cohort of patients frequently requiring multiple procedures. The potential challenges include technical difficulty in placement because of skeletal deformity and positioning of the child and the possible presence of a bleeding diathesis, although no epidural haematoma associated with a neuraxial technique has been reported. These challenges may be particularly relevant in patients with the more severe forms of OI.

Conclusions

Osteogenesis imperfecta is a rare multisystem disease characterised by primary bone fragility with heterogeneous clinical features and severity, and children with OI may present multiple times for orthopaedic and other types of surgery. The classification of OI is constantly evolving with new gene variants being discovered. In this review, we have discussed aspects of perioperative management, including preoperative investigations, airway management and intraoperative monitoring, and aspects of postoperative pain management, including the use of regional anaesthesia. Close liaison with the other members of the multidisciplinary team to formulate a coherent perioperative plan ensures the best chance for a successful outcome.

Declaration of interests

The authors declare that they have no conflicts of interest.

Acknowledgements

The authors thank Dr Claire McCahill, consultant paediatric anaesthetist, Great Ormond Street Hospital for Children (GOSH), for use of the data from the GOSH internal service evaluation entitled ‘Perioperative Management of Children with Osteogenesis Imperfecta’. The authors also thank Mr Yaser Jabbar, consultant paediatric orthopaedic surgeon, GOSH, for his advice regarding the use of surgical tourniquets in patients with osteogenesis imperfecta.

Biographies

Edmund Chan MA FRCA MAcadMed is a specialty registrar in London. He has undertaken training in paediatric anaesthesia at Evelina London Children's Hospital and at Great Ormond Street Hospital for Children.

Catherine DeVile MA MD FRCPCH FRCP is a consultant paediatric neurologist at Great Ormond Street Hospital for Children and is lead for their highly specialised osteogenesis imperfecta service.

Vineetha Ratnamma DA MD FRCA is a consultant in paediatric anaesthesia at Great Ormond Street Hospital for Children. Her subspecialty interests are renal, renovascular, orthopaedic and general paediatric surgery.

Matrix codes: 1A01; 1C01; 2D02; 2D05; 2G01; 3D00

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