A clinical team has documented the first published perioperative anaesthetic management of a paediatric patient diagnosed with DeSanto-Shinawi syndrome, an exceedingly rare autosomal dominant neurodevelopmental condition with fewer than fifty cases reported worldwide. Writing in the Egyptian Pediatric Association Gazette, researchers detailed how a multimodal anaesthetic regimen centered on propofol and remifentanil total intravenous anaesthesia, objective neurological depth monitoring, quantitative neuromuscular tracking, and cautious malignant hyperthermia preparedness enabled an extended dental procedure to proceed without adverse events. Because no prior clinical literature or pharmacological guidelines existed to direct anaesthesia in this ultra-rare condition, the case provides an empirical reference point for managing complex syndromic patients while underscoring that broader safety across the syndrome cannot be established from a single observation.
DeSanto-Shinawi syndrome is caused by heterozygous loss-of-function variants or microdeletions affecting the WAC gene located on chromosome 10p12.1. First characterised in 2015, the syndrome arises because the WAC protein serves as an obligate partner to the RNF20 and RNF40 ubiquitin ligase complex, regulating the monoubiquitination of histone H2B at lysine 120. This epigenetic mark is essential for chromatin organisation and transcriptional elongation, meaning that haploinsufficiency disrupts transcriptional programmes critical for normal neurodevelopment. Clinically, affected individuals display global developmental delay, variable intellectual disability, speech and language deficits, and distinct behavioural abnormalities such as autistic features, hyperactivity, and aggression. Other reported manifestations include epilepsy, sensorineural hearing loss, strabismus, gastrointestinal difficulties, and characteristic craniofacial dysmorphic features including a broad forehead, midface retrusion, a depressed nasal bridge with a bulbous tip, and deep-set eyes.
Before undertaking the procedure, the clinicians conducted a targeted literature search across PubMed, Embase, and Scopus using terms combining DeSanto-Shinawi syndrome, the WAC gene, and 10p12 deletions with anaesthesia, perioperative care, and surgery, finding zero recorded cases up to mid-2026. The patient, an eleven-year-old boy weighing 35 kilograms with an American Society of Anesthesiologists physical status classification of II, had molecularly confirmed DeSanto-Shinawi syndrome resulting from a 2.8-megabase heterozygous deletion at 10p12.1p11.23 encompassing WAC. He also carried a comorbid diagnosis of atypical autism spectrum disorder and was scheduled for multiple dental treatments requiring general anaesthesia. His surgical history noted early childhood operations for strabismus and right orchidopexy for cryptorchidism, which the family reported were uneventful, though the exact anaesthetic agents utilised during those procedures were unavailable for retrospective clinical review.
Preoperative assessment by paediatric anaesthesia and paediatric dentistry revealed notable phenotypic features that dictated technical planning. The child displayed classical craniofacial dysmorphisms, walked with support, and demonstrated functional hand use without spasticity or clinically significant hypotonia. Airway evaluation documented a Mallampati class II oropharynx without retrognathia, macroglossia, or cervical mobility limitation, yielding an initial low predicted airway difficulty score while recognising that dysmorphic facial features remained potential risk modifiers. Laboratory investigations, coagulation profiles, blood counts, and metabolic panels were completely normal, and the patient took no chronic medications and had no recorded drug allergies. To address behavioural impairment and environmental distress, the team avoided pharmacological premedication and instead maintained continuous caregiver presence and non-pharmacological distraction, facilitating successful first-attempt peripheral intravenous cannulation in the induction area without observable behavioural distress.
Anaesthetic planning balanced multiple pharmacological and physiological uncertainties, including potential airway alterations, communicative limitations, unknown central nervous system drug sensitivity, and the inability to definitively exclude malignant hyperthermia susceptibility in an uncharacterised genetic condition. Although DeSanto-Shinawi syndrome is not recognised as a malignant hyperthermia disorder and the patient’s 10p12.1p11.23 deletion involves neither RYR1 nor CACNA1S, the team adopted a conservative trigger-free strategy. Propofol and remifentanil total intravenous anaesthesia was chosen to circumvent halogenated inhalational vapours and depolarising muscle relaxants completely. In accordance with institutional malignant hyperthermia preparedness protocol, dantrolene sodium vials sufficient to provide a maximum cumulative dose of 20 milligrams per kilogram were kept immediately available in the operating room in an unreconstituted state.
Following standard preoxygenation for three minutes, anaesthesia was induced with intravenous fentanyl at one microgram per kilogram, propofol at 2.5 milligrams per kilogram, and the non-depolarising neuromuscular blocker rocuronium at 0.6 milligrams per kilogram. Nasotracheal intubation was chosen to provide unimpeded surgical access to all oral quadrants, maintain tube stability during operative manipulation, and permit uninterrupted evaluation of dental occlusion. After preparing the nasal mucosa with topical 0.05 percent xylometazoline hydrochloride, a 6.0-millimetre cuffed spiral-reinforced nasal tube was advanced smoothly through the right naris without resistance or mucosal epistaxis. Videolaryngoscopy paired with Magill forceps guided the tube into the trachea under direct visualisation, bilateral equal ventilation was confirmed by auscultation and end-tidal capnography, and a pharyngeal pack was placed to safeguard against pulmonary aspiration of blood and surgical debris.
General anaesthesia was maintained for approximately three hours using separate continuous syringe pump infusions of propofol delivered between 6 and 12 milligrams per kilogram per hour and remifentanil titrated between 0.05 and 0.15 micrograms per kilogram per minute. Mechanical ventilation remained in a volume-controlled mode delivering 6 to 8 millilitres per kilogram with 5 centimetres of water positive end-expiratory pressure in a 0.50 fraction of inspired oxygen. Depth of anaesthesia was continuously tracked using the Bispectral Index, targeting values between 40 and 60, while raw electroencephalography confirmed the absence of burst suppression or paradoxical signal elevation. Neuromuscular blockade was simultaneously monitored using continuous quantitative train-of-four acceleromyography over the adductor pollicis muscle. Haemodynamic parameters, oxygen saturation, end-tidal carbon dioxide, and body temperature remained completely stable throughout, with no indications of malignant hyperthermia such as hypercapnia, tachycardia, or muscular rigidity.
Analgesia during the dental operation relied on a systemic multimodal approach comprising the induction fentanyl, the continuous remifentanil infusion, and a single intraoperative dose of intravenous paracetamol at 15 milligrams per kilogram. The dental team administered no local anaesthetic infiltration or regional nerve blocks, aligning with evidence showing inconsistent proof that intraoperative local anaesthesia reduces postoperative pain after paediatric dental treatment under general anaesthesia. Surgical blood loss remained minimal throughout the procedure. Rescue airway devices, including a range of paediatric laryngeal mask airways and a dedicated fibreoptic bronchoscope, remained immediately present at the bedside across all operative phases, providing rapid escalation pathways had unexpected anatomical obstruction or ventilatory failure emerged.
Upon surgical completion, intravenous infusions of propofol and remifentanil were discontinued, the pharyngeal pack was removed under direct vision, and the oral cavity was thoroughly cleared of secretions. Quantitative acceleromyography confirmed that neuromuscular block had spontaneously recovered to a moderate depth, defined by a train-of-four count of two or more twitches. The clinicians administered intravenous sugammadex at two milligrams per kilogram, achieving full objective neuromuscular recovery with a train-of-four ratio of at least 0.9 prior to extubation. The patient demonstrated regular spontaneous breathing with sufficient tidal volumes, allowing smooth removal of the nasotracheal tube under direct laryngoscopy. The objective confirmation of chemical reversal proved particularly vital because communicative impairments in the patient precluded reliance on conventional clinical extubation criteria like voluntary respiratory effort and command-following.
The patient was transferred in stable condition to the post-anaesthesia care unit, where he achieved a modified Aldrete score of 10 within one hour of monitored observation. He exhibited no postoperative nausea and vomiting, respiratory compromise, bleeding, or emergence agitation, returning smoothly to his baseline cognitive and behavioural state before being discharged home from the day-surgery ward that same afternoon. Telephone follow-up with the family on postoperative days 1 and 7 confirmed the absence of any delayed respiratory, behavioural, or surgical complication. The authors noted that the rapid offset kinetics of remifentanil and the antiemetic properties of propofol are particularly advantageous in this population, in which turbulent or prolonged emergence carries the risk of self-injury and refractory agitation.
Discussing the genetic and pharmacological context, the clinicians emphasised that while DeSanto-Shinawi syndrome patients typically share core features such as developmental delay, autistic behaviours, and distinct facial dysmorphisms, large contiguous deletions like the 10p12.1p11.23 deletion present here can induce expanded phenotypes. In this child, haploinsufficiency of flanking genes adjacent to the WAC locus accounted for cryptorchidism, a feature absent in isolated point mutations. Although Bispectral Index monitoring operated reliably in this child, who had no history of epilepsy or spike-wave discharges, the authors cautioned that depth indices have never been validated across the syndrome and must remain secondary adjuncts to clinical monitoring. Ultimately, while this initial case demonstrates that trigger-free total intravenous anaesthesia paired with objective neuromuscular and depth monitoring was feasible, establishing safety across the syndrome will require the accumulation of further reported experience.
Subject of Research: Perioperative anaesthetic management of a paediatric patient with DeSanto-Shinawi syndrome
Article Title: Anaesthetic management of a child with DeSanto-Shinawi syndrome: a case report
Article References: Gürbüz, Ö. K., Çolak, Y. Z., Gülhaş, N., & Fettahlıoğlu, A. (2026). Anaesthetic management of a child with DeSanto-Shinawi syndrome: a case report. Egyptian Pediatric Association Gazette, 74(1), Article 86. https://doi.org/10.1186/s43054-026-00591-8
Image Credits: AI Generated
DOI: 10.1186/s43054-026-00591-8
Keywords: DeSanto-Shinawi syndrome, paediatric anaesthesia, total intravenous anaesthesia, propofol, remifentanil, sugammadex, rocuronium, nasotracheal intubation, malignant hyperthermia preparedness, bispectral index monitoring, train-of-four acceleromyography, WAC gene deletion, autism spectrum disorder, dental surgery, case report, rare genetic disorders
