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Anaesthesia for orphan disease: Management of an infant with Silver–Russell syndrome

Passier, Roeland H.A.; Verwijs, Edwin; Driessen, Jacques J.

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European Journal of Anaesthesiology: June 2014 - Volume 31 - Issue 6 - p 336-338
doi: 10.1097/EJA.0000000000000013

Editor,

Silver–Russell syndrome (SRS) is a heterogenous syndrome characterised by a variable combination of intrauterine growth retardation, postnatal dwarfism with relative macrocephaly and a typical facial appearance including a triangular shaped face, frontal bossing, downturned corners of the mouth with a small opening and micrognathia. Other features include limb and body asymmetry and fifth finger clinodactyly. Feeding difficulties are also seen in the majority of affected children.1–4 The syndrome derives its name from two doctors, Silver and Russell, who independently described children with this combination of clinical features in the 1950s.5,6 The incidence is around 1 per 100 000 live births.7 There are two main genetic subgroups of SRS children with limited phenotypical differences: methylation abnormalities of chromosome 11p15 and maternal uniparental disomy of chromosome 7 (mUPD7). In a significant number of patients, however, the molecular cause is not known.3 Most cases of SRS are sporadic, although in some patients, the syndrome seems to have a familial background.2,4

Literature on the anaesthetic implications of SRS is scant with a first case report published almost 20 years ago.8 Only a couple of cases have been published since, which are either dated, dealing with an older child and/or not readily accessible due to being in Japanese.9,10,11 We describe the anaesthetic management of a child with SRS in an attempt to increase awareness about anaesthesia in children with rare diseases and in particular, those with SRS. Consent was obtained from the parents to publish this report.

A 3-year-old adopted child, weighing 9 kg, was admitted to our hospital for laparoscopic investigation of a nonscrotal testis and completion of the first stage of a Fowler-Stephens procedure. At the time of adoption about a year earlier, it was communicated that he had hypospadias and cryptorchidism, with an otherwise unremarkable past medical history, without any previous general anaesthetics. On medical examination in The Netherlands, ambiguous genitalia and severe growth retardation were noted. His psychomotor development and intelligence seemed normal for his age. He was diagnosed with SRS after genetic investigation.

On preoperative assessment, it was found he had a short stature and craniofacial dysmorphy including a small mouth with limited opening and mandibular hypoplasia, predicting potential difficulty with airway management (Figure 1). There was no history of feeding difficulties or episodes of hypoglycaemia.

Fig. 1
Fig. 1:
No captions available.

The child was premedicated on the ward with oral midazolam 4 mg and rectal paracetamol 240 mg. As a difficult airway and endotracheal intubation were anticipated, we planned to perform an inhalational induction of anaesthesia with sevoflurane and to maintain spontaneous respiration until tracheal intubation had been successfully achieved. A GlideScope (Blade 2; Verathon Inc., Bothell, Washington, USA) and paediatric fibreoptic bronchoscope (3.2 mm; Olympus Corporation, Tokyo, Japan) were immediately available in case direct laryngoscopy proved to be unsuccessful in securing the airway. The patient was positioned on a forced-air warming blanket to maintain normothermia and standard monitoring was applied including noninvasive blood pressure, ECG, pulse oximetry and capnograpy. Induction of anaesthesia was accomplished by inhalation of sevoflurane 6 to 8% in 100% oxygen by facemask, after which peripheral intravenous access was secured with a 24-gauge intravenous cannula. Mask ventilation was performed without difficulty by one person, without the need for an oropharyngeal or nasopharyngeal airway. Direct laryngoscopy was performed after intravenous administration of fentanyl titrated to a total of 20 μg and without the use of neuromuscular blocking agents in order to maintain spontaneous ventilation. The patient had a very small oral opening and an anterior larynx and only after significant external laryngeal manipulation and downward pressure was a Cormack and Lehane grade III view obtained. Tracheal intubation was performed using a 4.5 mm internal diameter cuffed endotracheal tube (Mallinckrodt Pharmaceuticals, Dublin, Ireland), which was passed easily on the first attempt. The cuff was left deflated, as there was no clinically significant air leak. We opted not to exchange the endotracheal tube for a size smaller as there was no resistance on passing the tube into the trachea and we wished to avoid multiple intubation attempts. The patient was artificially ventilated and maintenance of anaesthesia was achieved with sevoflurane (end-tidal concentration around 2.5%) in oxygen and air. A further 15 μg of fentanyl was administered intravenously during the case. Further anaesthetic management and surgery proceeded uneventfully. Local infiltration of the incisional wounds with 1.5 ml of bupivacaine 0.25% with adrenaline 1 : 200 000 was performed by the surgeon at the end of the case. The trachea was extubated with the child awake and only after return of airway reflexes. During the surgery, the child received a total of 140 ml of a combined glucose 3.3% and NaCl 0.3% infusion to compensate for fasting and maintenance requirements, followed postoperatively by a 50 ml h−1 infusion of lactated Ringer's solution until sufficient oral intake was restored. Postanaesthesia care was uneventful and the child was discharged to the ward later the same day.

The complex genetic characteristics of children with SRS have been extensively reported.2 A cohort of 38 Dutch children with a diagnosis of SRS proven by clinical and molecular means was recently published. It is noteworthy that a high proportion of these children were conceived as a result of assisted reproductive techniques.1

This child had a confirmed diagnosis of SRS as he was found to have a hypomethylation of the H19-gene on chromosome 11. This is the cause of SRS in the majority of cases. Methylation disorders on chromosome 11p15 contain a cluster of imprinted genes involved in fetal growth. This cluster is organised in two neighbouring imprinted domains, IGF2/H19 and the KCNQ1OT1/CDKN1C. A less frequent cause of SRS is mUPD7, which is reported to cause a milder phenotype.3 Aberrant genomic imprinting of the 11p15 region is involved in both SRS and Beckwith–Wiedemann syndrome (BWS):2,12 hypomethylation at H19 causes the first, whereas hypermethylation at the same location causes the latter. SRS is characterised by growth retardation, whereas BWS is associated with pre and/or postnatal overgrowth.

Anaesthetic considerations for SRS include airway management as a primary challenge: the facial dysmorphy with small mouth opening and mandibular hypoplasia may result in difficult mask ventilation, laryngoscopy and tracheal intubation. In addition, subglottic stenosis may be present. The child in our case had a Cormack and Lehane grade III view of the larynx on direct laryngoscopy. At present, we do not know whether this could worsen with the progression of the syndrome, although it is well recognised that the facial features of SRS tend to become less obvious with age.

Children with SRS may also face other anaesthesia-related problems due to the characteristic clinical features. In contrast to the case we presented, many SRS children suffer from various endocrinopathies, such as hypopituitarism and adrenal insufficiency. Hypoglycaemia is the most common associated problem. It occurs in a large percentage of neonates, but decreases in frequency by the age of 4 years.8,10 Children with SRS are prone to develop spontaneous hypoglycaemia, especially if they are not fed regularly, most likely due to accelerated starvation and/or growth hormone insufficiency.13 When anaesthetising these children, precautions should be taken to guard against hypoglycaemia, even in patients who are over the most susceptible age and who have not had any previous episodes of hypoglycaemia.14 In addition, SRS patients (especially infants) are prone to hypothermia due to the abnormally (relatively) large cranial size and the lack of muscle mass and subcutaneous fat.8,10 They may have feeding difficulties and gastro-oesophageal reflux. The latter may cause additional problems in airway management, especially in emergency situations.3,15 Psychomotor retardation is present in around one-third of patients with SRS. Associated congenital anomalies including cleft palate, congenital heart disease, genital anomalies and limb defects are described in a minority of cases. Finally, SRS patients with mUPD7 abnormality are at an increased risk of developing dystonia and myoclonus.3

The current treatment of SRS consists of recombinant growth hormone administration for which the beneficial effects are dependent upon the early institution of the therapy. This treatment is effective in the short-term, although studies examining the long-term effects are lacking.4

In conclusion, SRS is a clinically recognisable syndrome, which has important implications for safe anaesthesia management, primarily due to possible difficulties in airway management. In addition, care should be taken to ensure glucose homeostasis and proper temperature management. Awareness of possible associated congenital anomalies, such as other endocrinopathies and congenital heart disease, will contribute to optimal anaesthetic care in children with this syndrome.

Acknowledgements relating to this article

Assistance with the study: the authors would like to thank Professor Dr H. Brunner for his assistance with the report.

Financial support and sponsorship: none.

Conflicts of interest: none.

References

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