February 7, 2022
by Abbass Saleh, DDS, MSc (Candidate); Amanda Vincci Chiu, DDS, MSc (Candidate)
Cornelia de Lange Syndrome (CdLS) is a rare genetic neurodevelopment disorder that can present challenging behavioral and airway management during general anesthesia. This case report involves a 25-year-old female patient with CdLS who received a moderate sedation for dental treatment at the Adult Surgicentre, Faculty of Dentistry, University of Toronto. CdLS is associated with developmental delays, possible challenging airway, seizure disorder, gastroesophageal reflex, autonomic dysfunction, and various sensitivities to certain medications. Our patient was investigated to understand her full medical and past anesthetic history. She has a mild form of CdLS and was appropriately selected for ambulatory outpatient moderate sedation to facilitate comprehensive dental treatment, including a dental exam, radiographs, hygiene procedures, and direct restorations. This initial anesthetic appointment was used to create a suitable and predictable anesthetic plan for subsequent moderate sedation appointments.
Cornelia de Lange Syndrome (CdLS), also known as Brachmann-de Lange Syndrome, Amsterdam Dwarfism or Bushy Syndrome, is a rare genetic neurodevelopmental disorder. It was first described by Cornelia de Lange in 1933 in Amsterdam.1,2 The prevalence is reported to be around 1/10,000-50,000 newborns, with no sexual predominance.1,2 CdLS is characterized by multiple congenital anomalies, including neurodevelopmental disabilities such as growth, mental and/or psychomotor retardation, seizures, vision and hearing abnormalities, and behavioural problems (i.e. autistic-like behavior). Furthermore, CdLS patients present typical craniofacial characteristics and other physical findings such as facial dysmorphism, limb deficiency defects (short or missing limbs), bushy fused eyebrows and excessive body hair. Other commonly associated anomalies include cardiovascular lesions, pulmonary aspiration secondary to gastroesophageal reflux disease (GERD), and renal anomalies.
Although this disorder can present in variable severities, the most common challenges reported during anesthetic management of patients with CdLS include issues related to airway difficulty, gastroesophageal reflex, autonomic dysfunction, various sensitivities to both intravenous and volatile anesthetics and depolarizing skeletal muscle relaxants.3,4
We report a case in which a CdLS patient received ambulatory out-patient moderate sedation who had minimal risk factors for developing perioperative complications. This could have proven to be a very difficult anesthetic if the patient had a severe level of disease, the patient’s medical history was not fully understood, or investigation was not completed. This is a demonstration of adequate medical investigation, proper physical and airway examination, and appropriate case selection to provide a CdLS patient with dental treatment under moderate sedation.
A 25-year-old female (155 cm, 70 kg, body mass index 28 kg/m2), who required sedation for treatment of dental caries was referred to the Adult Surgicentre at the University of Toronto. She was accompanied by her mother who was aware of the patient’s dental needs and lack of cooperation for treatment while awake or under minimal sedation.
Her medical history was significant for Cornelia de Lange Syndrome, seizure disorder, developmental delay, innocent heart murmur, anxiety, and depression. Her medications included divalproex (Epival®) and ethinylestradiol/levonorgestrel (Alesse®). She did not report any drug allergies or previous adverse reaction to dentistry or sedation. She was compliant with divalproex, an anticonvulsant, and her last reported seizure was more than 10 years ago. Her American Society of Anesthesiologists Physical Status Classification was III.
She underwent an echocardiogram in 2018 and electrocardiogram (EKG) in 2020. Her echocardiogram showed no evidence of left ventricular dysfunction, structural changes, wall-motion abnormalities, and a preserved ejection fraction (55%). There was no evidence of diastolic dysfunction. There was also no evidence of right ventricular dysfunction or structural change. There was no indication of major valvular abnormalities. Her EKG showed a normal sinus rhythm with no indication of previous pathological processes. Overall, the echocardiogram and EKG findings were within normal limits. The patient reported no changes in her daily function (METS evaluated to be greater than 4) or symptomatology since these investigations, hence we elected to not repeat these investigations.
This patient had a mild form of CdLS, which was well supported by her medical history, minimal daily medications, and pre-operative investigations, including cardiac testing and a lack of pertinent positives in a complete review of systems. At this time, it was determined that the patient was medically optimized for ambulatory outpatient dental care under moderate sedation.
Airway and Cardiopulmonary Examination
A complete and thorough airway examination revealed a possible but unlikely airway challenge. The patient had evidence of mild micrognathia and retrognathia with an inability to perform an Upper Lip Bite Test (score 3). She was able to open her mouth without difficulty and there was no limitation in neck mobility. The patient did not have a recent upper respiratory tract infection, and her mother reported no evidence of snoring or airway obstruction during sleep.
Pulmonary auscultation indicated clear bilateral air entry with no evidence of adventitious sounds such as a wheeze, rhonchi, or crackles. Cardiac auscultation was within normal limits, even though the patient was diagnosed with a mild innocent heart murmur, it could not be detected at the time of examination.
Peri-operative and Post-Operative Management
The medical history was reviewed for any changes on the day of the appointment. The patient had followed the minimum duration of fasting, including three hours for clear liquids and eight hours for solid food as per the sedation protocol guidelines by the Royal College of Dentistry of Ontario (RCDSO) Standard of Practice for Sedation and Anaesthesia.5 A 22-gauge intravenous catheter was placed in the right dorsum of the hand, and standard monitoring was used, including continuous capnography and a pre-tracheal stethoscope. The pre-induction vital signs included: blood pressure of 144/88 mmHg, pulse rate of 92 beats per minute, oxygen saturation of 100% on room air, and a respiratory rate of 16 breaths per minute. The patient was positioned in the dental chair and pre-oxygenated at 6 L/min via a nasal hood prior to induction. Sedation commenced with a combination of 40% nitrous oxide and slow incremental intravenous boluses of 1 mg midazolam. The patient also received a moderate dose of 0.2 mg glycopyrrolate for its antisialagogue effect. A moderate level of sedation was achieved and maintained, which is defined as a purposeful response to verbal command or tactile stimulation. At this time, dentistry was carried out comfortably. Incremental intravenous boluses of 1 mg midazolam were given during the procedure to maintain the depth of anesthesia to a total of 4 mg midazolam. The patient required bilateral inferior alveolar block to tolerate dental radiographs. A complete dental examination, scaling, polish, fluoride treatment and operative dentistry was carried out with the mother’s and patient’s consent. The patient recovered in the dental chair uneventfully and was discharged when all vitals were stable, and when the patient was oriented to person, place, and time.
The primary goal of this article was to enable general dentists to appreciate the complexity and challenges that can arise with parenteral sedation for patients with craniosynostosis and/or craniofacial disorders.
Patients with CdLS may have a difficult airway due to high incidence of a high-arched palate, small mouth opening, and micrognathia. It is imperative to have a thorough airway assessment and recognize that some patients may present with unexpected challenging airways.3,6,8 Craniofacial dysostosis can make both bag-mask ventilation and use of an advanced airway challenging. A case report series of six patients with CdLS found an incidence of challenging intubation in 50% of the patients.7 Consequently, minimizing the risk of apnea is of utmost importance. If intubation is required, a smaller endotracheal tube size will best accommodate the commonly narrowed space for the vocal cords and trachea.3
Also, CdLS presents as a wide spectrum of disease ranging from mild to severe presentation. Our patient had a mild presentation, which allowed us to provide a safe anesthetic in an ambulatory setting. She was cooperative with establishing intravenous access and the anaesthetic process, which is not always the case in patients with behavioural issues secondary to cognitive dysfunction. In these scenarios, the anesthesia provider may be required to combine the use of non-pharmacological and pharmacological behavioral management. Also, it is worth remembering that peripheral limb deficiency in severe cases of CdLS can make intravenous access challenging.3
As previously mentioned, CdLS is a genetic disorder with multi-systemic effects, including gastro-intestinal, renal, respiratory, and cardiac disorders. Patients are at a higher risk of intraoperative aspiration pneumonia due to GERD.3 Our patient did not report any symptoms or show signs of GERD. She had clear bilateral air entry and a negative history of shortness of breath, wheezing, and dyspnea. Her recent cardiac testing included a normal echocardiogram, EKG and cardiac physical exam, which reduced the likelihood of an occult cardiac malformation. Patients with CdLS can exhibit various medication sensitivities, including to opioids and benzodiazepines, and can have paradoxical responses to these medications.9 A thorough preoperative consult to understand and mitigate the risks of poor perioperative and postoperative outcomes is essential.
It can be extremely rewarding to provide dentistry to syndromic patients with neurodevelopmental delays. Sedation can facilitate dental care, with safety as the utmost priority. The anesthetic care of the patient with CdLS is often complex and challenging. A carefully considered perioperative and postoperative plan can decrease morbidity and mortality. Understanding the multi-systemic involvement of syndromes can help understand the possible challenges and complications that can arise. Choosing the minimal or moderate levels of sedation to enable care and planning for a shorter appointment may improve safety. In this case, the idiom of “less is more” still stands true.
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About the Author
Dr. Amanda Vincci Chiu received her DDS from the University of Toronto, Faculty of Dentistry. She completed a hospital dental residency at Sunnybrook Health Sciences Centre before returning to pursue her specialty training in dental anesthesia at the University of Toronto. She has also been providing dental care to Indigenous communities.
Dr. Saleh is a Montreal native and obtained his doctorate in Dental Medicine at the University of Montreal in 2015. He did contracts in Kuujjuaq in Northern Quebec and Moose Factory in Northern Ontario, which led to an opportunity to work full-time in Moose Factory for the Weeneebayko General Hospital (WAHA). He is now pursuing a masters degree in Dental Anesthesiology.