Anesthetic management of a 9-year-old girl with Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay syndrome: airway difficulties and postoperative apnea during tendon surgery
Article information
Abstract
Background
This case report described the anesthetic management and postoperative challenges of a patient diagnosed with Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay (CLIFAHDD) syndrome who underwent tenomyotomy of the right hand tendons. This syndrome, characterized by facial dysmorphisms, musculoskeletal abnormalities, and respiratory disturbances, including central apnea, is caused by a mutation in the NALCN gene.
Case
A 9-year-old girl diagnosed with CLIFAHDD syndrome underwent tenomyotomy of the right hand tendon. General anesthesia was administered. Despite stable intraoperative conditions, the patient experienced inadequate ventilation with multiple episodes of apnea after extubation, necessitating assisted ventilation using a face mask.
Conclusions
This case highlights the challenges and considerations in the anesthetic management of patients with CLIFAHDD syndrome, emphasizing the need for tailored approaches and vigilant postoperative monitoring to mitigate the potential respiratory complications associated with this rare genetic disorder.
Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay (CLIFAHDD) syndrome is a rare genetic disorder characterized by congenital limb and facial contractures, hypotonia, and global developmental delay [1]. This syndrome has recently been linked to mutations in the sodium leak channel gene (NALCN), which plays a critical role in regulating neuronal excitability and maintaining the resting membrane potential of neurons [1,2].
The implications of these mutations are profound, affecting not only neurological function but also presenting unique challenges during medical procedures, especially intubation and extubation. The complexity of CLIFAHDD syndrome is further exacerbated by associated respiratory issues including central and obstructive sleep apnea and a heightened sensitivity to anesthetic agents [2,3]. The interplay between the neurological impacts of the syndrome and its effects on respiratory function necessitates a tailored anesthetic approach. Careful preoperative assessment and meticulous intraoperative monitoring are essential.
In this case report, we described a 9-year-old patient with CLIFAHDD syndrome who underwent orthopedic surgery under general anesthesia, along with a literature review. By detailing the clinical presentation and specific anesthetic challenges faced during extubation, this case report contributes to an enhanced understanding of the anesthetic considerations in patients with CLIFAHDD syndrome. To date, the appropriate anesthetic management of these patients has not been published.
CASE REPORT
A 9-year-old girl underwent tenomyotomy of the tendons in her right hand at Joana de Gusmão Children's Hospital, Florianopolis, SC. A consent form was signed by the child's parents, who also authorized the publication of this case report, except for the photographic material. The patient was born at term (38 + 5 weeks) by cesarean section due to gestational hypertensive disease and multiple repeat cesarean sections. At birth, microstomia, short neck, hand-digit malformations, and micrognathia were observed. The patient was admitted to the Neonatal Intensive Care Unit until the tenth day of life because of respiratory insufficiency. Cardiorespiratory arrest due to apnea occurred at 40 days of age. After genetic investigation, the patient was diagnosed with CLIFAHDD syndrome (confirmed by exome sequencing, which revealed a missense point mutation: c. 1733A > G p. Tyr578Cys). The guardian reported prior use of Bilevel Positive Airway Pressure (BiPAP) by the patient, although it had not been necessary in the last year. The patient did not take any medications and had no known allergies. The patient had undergone two general anesthesia procedures (tonsillectomy at 7 years of age and correction of congenital clubfoot at 3 years of age). According to her parents, both procedures involved episodes of apnea that required an extended postoperative hospital stay. However, this information could not be found in the medical records.
At the time of surgery, the patient weighed 39 kg and had normal cardiopulmonary auscultation, an oral opening of less than 2 cm, Mallampati IV, and a thyromental distance of less than 3 cm. She had a high-arched palate, micrognathia, and thoracic scoliosis. She had fasted for 8 h and had no history of recent upper respiratory viral infection. Laboratory test results were within normal limits.
Standard monitoring included noninvasive blood pressure measurement, electrocardiography, oximetry, and neuromuscular monitoring using an acceleromyography device with ulnar nerve stimulation. Peripheral access was obtained in the right upper limb using a 22-gauge Abocath, and venous induction was performed. Despite the predictors indicating an at-risk airway, the medical records indicated no difficulties with previous intubation. Thus, induction was performed with fentanyl 2 mcg/kg, propofol 3 mg/kg, and atracurium 0.4 mg/kg. Direct laryngoscopy was performed after uneventful ventilation, revealing Cormack-Lehanne IIa, followed by orotracheal intubation with a 6.0 cuffed tube. Ventilation was performed in the pressure-controlled mode, providing 8 ml/kg. Anesthesia maintenance was performed with 1.6% sevoflurane (maintaining 0.8 MAC). Hydration was maintained with Ringer's lactate at 156 ml/h. dexamethasone 0.15 mg/kg, dipyrone 30 mg/kg, and ondansetron 0.1 mg/kg were administered. The procedure proceeded without complications, and hemodynamic stability was maintained throughout.
One and a half hours after induction and upon completion of the procedure, the airway was suctioned, and recovery from neuromuscular blockade was confirmed using neuromuscular stimulation monitoring (train of four [TOF] ratio > 90%). However, after the patient resumed spontaneous ventilation, she experienced intermittent apnea episodes. She had a tidal volume of less than 5 ml/kg despite the absence of residual neuromuscular blockade (confirmed with a repeat TOF ratio of over 90%) and an expiratory end-tidal sevoflurane concentration of 0.1%. Mechanical ventilation in the pressure-support mode was maintained until the patient achieved a spontaneous tidal volume greater than 5 ml/kg and was fully awakened approximately 30 min later. Extubation was performed after confirming that the patient had conjugate gaze, facial grimace, eye opening, and purposeful movement, and maintained adequate tidal volume and respiratory rate without apnea.
After extubation, the patient presented with episodes of apnea and required assisted ventilation with a facemask. After approximately 30 min of being apnea-free, and with the maintenance of adequate oxygen saturation and spontaneous ventilation, the patient was sent to the post-anesthetic recovery room on supplemental oxygen therapy with an open mask at 2 L/min. A good ventilatory pattern was observed. After discharging the patient to the inpatient pediatric unit, her vital signs were monitored. No new episodes of apnea arose and the patient was discharged two days later.
DISCUSSION
In this case, a patient with CLIFAHDD syndrome presented with extubation difficulties owing to episodes of apnea. CLIFAHDD syndrome is a rare syndrome [1]. To date, the appropriate anesthetic management of patients with this syndrome has not been reported. The condition is caused by mutations in the sodium leak channel gene (NALCN) [1]. This channel is widely expressed in the central nervous system, contributing to basal Na+ leakage conductance and the regulation of neuronal excitability. It is a non-selective cationic channel that contributes to the resting membrane potential of neurons and modulates its excitability [2]. Mutations in these channels are associated with hypotonia, psychomotor retardation, and facial alterations [3,4]. Recessive pathogenic variants have been associated with infantile hypotonia with psychomotor retardation and characteristic facial features (i.e. Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies syndrome). In contrast, dominant pathogenic variants have been associated with congenital limb and facial contractures, hypotonia, and global developmental delay (i.e. CLIFAHDD syndrome). The facial characteristics of affected individuals include eyelid lesions, broad nasal bridges with wide nostrils, anteverted nasal tips, small columella, long philtrum, and micrognathia. Additionally, these patients may present with lower limb deformities; contractures in the elbows, knees, and hips; short neck; and scoliosis [1].
Patients with this syndrome may experience circadian rhythm alterations, central apnea, and obstructive sleep apnea with recurrent hypoxia. Increased sensitivity to sevoflurane with significant respiratory depression at usual doses has also been described [5]. A study on Drosophila flies carrying NALCN mutations demonstrated an altered sensitivity to inhalational anesthetics [2].
The use of inhaled agents in our patient may have contributed to respiratory depression. A previous case report demonstrated increased sensitivity to benzodiazepines and barbiturates, indicating excessive sedation at sub-therapeutic doses [5]. Chong et al. [1] reported abnormal respiratory patterns in the neonatal period and respiratory failure in 2/3 of patients with CLIFAHDD syndrome. Studies in rats with NALCN mutations have demonstrated alterations in respiratory patterns with periods of apnea, similar to Cheyne-Stokes breathing [2]. In addition to respiratory changes, the gastrointestinal tract may also be involved. Gastroesophageal reflux disease is the most common gastrointestinal manifestation [6].
Our patient exhibited an irregular respiratory pattern during extubation, even after neuromuscular block reversal, with a low expired sevoflurane concentration. This may have been due to increased sensitivity to the anesthetics used and the occurrence of central apnea episodes, both of which have been previously associated with this syndrome.
For the anesthetic management of patients with CLIFAHDD Syndrome, several considerations are crucial due to the condition’s impact on respiratory function and the body’s response to anesthetic agents. In the preoperative period, abnormal respiratory patterns, neuromuscular function, and gastrointestinal issues were assessed. Moreover, we prepared for a potentially difficult airway and considered the possibility of regurgitation. Owing to the enhanced sensitivity to anesthetics, it is advisable to use lower doses and closely monitor respiratory function. Due to the potential for central apnea and abnormal respiratory patterns, we recommend careful monitoring of respiratory function and extubation planning. Appropriate ventilation support must be readily available. Mechanical ventilation should be considered if needed. Furthermore, confirm the complete reversal of the neuromuscular blockade and monitor any residual neuromuscular weakness. In our patient, objective monitoring (e.g., train-of-four monitor was used to the appropriate reversals). Furthermore, intensive monitoring provided in the recovery room to manage potential postoperative respiratory issues, and supportive care was provided as necessary.
In this case report, we provided insights into the anesthetic management of patients with CLIFAHDD syndrome, a rare and poorly understood condition. The varied clinical characteristics and complexity of CLIFAHDD syndrome require careful preoperative evaluation and an anesthetic strategy adapted to the specific needs of each patient. Increased sensitivity to certain anesthetic agents, such as sevoflurane, and a predisposition to respiratory disorders necessitate careful monitoring during all phases of the anesthetic procedure, particularly during the immediate postoperative period. Further research is needed to fully elucidate the anesthetic challenges associated with CLIFAHDD Syndrome. This case report contributed findings that can be used to guide clinical practice and anesthetic care for patients with CLIFAHDD syndrome.
Notes
FUNDING
None.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
DATA AVAILABILITY STATEMENT
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
AUTHOR CONTRIBUTIONS
Writing - original draft: Jessica G. Santos. Writing - review & editing: Jessica G. Santos, Alexandre C. Buffon. Supervision: Alexandre C. Buffon.