Anaesthesia and orphan diseases

Bohring–Opitz syndrome

Editor,

We write to describe the anaesthetic management of a patient with Bohring–Opitz syndrome (BOS), a rare sporadic genetic disorder characterised by various anomalies including among others a typical facial appearance, developmental delay and a typical posture, who has presented to our institution several times for both elective and emergency procedures. Information on the anaesthetic management of patients with this condition is very scarce in the literature. Parental consent was obtained for this case report.

Body systems affected of particular relevance to the anaesthetist include the cardiovascular, respiratory, gastrointestinal and musculoskeletal systems. BOS is an autosomal dominant condition first described in 1999 by Bohring et al.¹ and recognised as a separate entity from Opitz Trigonocephaly C syndrome. It is caused by mutations in the ASXL1 gene, most of which are believed to arise de novo.² Although its exact prevalence is unknown, at least 68 cases have been described in the scientific literature.³ While individuals with BOS often do not survive past childhood, a few reach adolescence or early adulthood.

The majority of patients with BOS have a normal head shape and size with a characteristic facial appearance, displaying exophthalmos, hypertelorism, upslanting palpebral fissures, a flat nasal bridge and anteverted nares, although significant variability is observed. However, some have abnormal craniofacial development, including manifestations such as microcephaly and micrognathia associated with difficult airways, requiring complex airway management.⁴

Idiopathic and transient bradycardias were widely reported in the initial literature that predated identification of the genetic basis of BOS. Cardiovascular deaths have been associated with this phenomenon and account for four (33%) of the 12 deaths published in the literature (although none of those individuals had a molecular confirmation of BOS).⁵ Other cardiac anomalies include septal defects and cardiac hypertrophy as well as one case report of double outlet right ventricle associated with aorto-pulmonary window.³

In addition to apnoea and bradycardia, respiratory infections are common in infancy and account for a further five of the 12 reported deaths. When chronic emesis is treated, or improves with age, the rate of respiratory infections decreases. Tracheostomies have been used to provide definitive airway protection in this setting.⁵

In most cases feeding issues have commenced in infancy, with general improvement or resolution often described in early childhood. Historically, feeding difficulties have been presumed to be secondary to severe gastroesophageal reflux, but initial case reports did not produce diagnostic evidence of gastroesophageal reflux or demonstrate improvement on traditional antireflux therapies. Recent publications have suggested a neurogenic cause, including cyclic vomiting with possible poor gastric motility, as the underlying cause of the chronic emesis. Given the frequency of emesis, there is a high risk for aspiration and dehydration, typically resulting in multiple hospitalisations.⁵

Those with the condition often have characteristic body positioning, known as BOS posture. This includes slouching of the shoulders, with bent elbows and wrists and ulnar deviation of the hands and wrists, while the legs are extended straight.⁶ Affected individuals usually stop exhibiting this posture as they get older. Other musculoskeletal abnormalities include joint contractures and abnormal muscle tone, making careful positioning during surgery difficult and crucially important.⁵

Our patient was a 5-year-old male. The background history was significant for severe developmental delay, epilepsy, scoliosis, dystonia and the patient was fed via a percutaneous enteral gastrostomy. He has undergone anaesthesia five times in our institution. Three times for elective or semi-elective procedures and twice as a result of intractable seizures requiring emergency transfer to a tertiary paediatric centre. Pre-operatively the challenges presented by this case were acknowledged, particularly the potential for a difficult airway. Intravenous access was noted to be difficult on three of the five occasions with one incidence of inadvertent subcutaneous administration of medication and on one occasion required the placement of a femoral central line. Two gas inductions were performed using a sevoflurane/oxygen mixture and three intravenous inductions were performed using fentanyl and propofol. When muscle relaxation was required mivacurium was used twice and rocuronium twice. The patient was intubated on four occasions with a size 4 cuffed endotracheal tube. On three occasions the patient was successfully intubated using a Macintosh size 2 blade and a stylet. A McGrath videolaryngoscope size 2 blade was successfully used as the primary choice once. Each intubation, involving three different anaesthesiologists, was noted to be difficult with a Cormac and Lehane score of 3. A size 2 laryngeal mask airway was used on one occasion. Each anaesthetic was maintained with a sevoflurane/oxygen/air mixture and proved uneventful. When the patient required transfer to a paediatric centre they were sedated with morphine and midazolam infusions. The patient was extubated at the end of three procedures uneventfully and following a routine period of observation in the postanaesthesia care unit was discharged to the ward, with no complications arising thereafter. Bradycardia or arrhythmia did not arise.

We wish therefore to draw this rare condition to the attention of the anaesthesia community, to alert them to the likelihood of difficulties with vascular and airway access and to offer them the benefit of our experience in managing it (Table 1).

Table 1 - Summary of anaesthetic episodes

	1	2	3	4	5
Age	5 Years 1 month	5 Years 2 months	5 Years 4 months	5 Years 5 months	5 Years 8 months
Weight (kg)	16.9	17.0	15.7	16.1	17.0
Procedure	PICC line insertion	Emergency intubation	PEG tube insertion	Manipulation under anaesthesia + casting of femur	Emergency intubation
Induction	Sevoflurane/Oxygen	Intravenous	Sevoflurane/Oxygen	Intravenous	Intravenous
Airway	LMA 2	Macintosh 2 4.0 cuffed ETT	Macintosh 2 4.0 cuffed ETT	Macintosh 2 4.0 cuffed ETT	McGrath 2 4.0 cuffed ETT
Medications	–	Propofol, fentanyl, rocuronium	Fentanyl, mivacurium	Fentanyl, mivacurium	Fentanyl, rocuonium, propofol
Difficult intravenous access	No	Yes	No	Yes	Yes
Complications	No	No	No	Subcutaneous drug administration	No
Post Op analgesia	–	Transfer to paediatric centre	Paracetamol	Paracetamol, Oramorph	Transfer to paediatric centre

ETT, endotracheal tube; LMA, laryngeal mask airway; PEG, percutaneous endoscopic gastrostomy tube; PICC, peripherally inserted central catheter.