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Anaesthesia and orphan disease: the child with 3M syndrome

Tsiotou, Adelais G.; Malisiova, Anna; Kalliardou, Evangelia

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European Journal of Anaesthesiology: December 2012 - Volume 29 - Issue 12 - p 598-600
doi: 10.1097/EJA.0b013e32835a9a6c

Editor,

3M syndrome is a recessive autosomal genetic growth disorder, characterised by significant prenatal and postnatal growth retardation.1 3M syndrome is listed as a rare or an ‘orphan’ disease having a prevalence in Europe of less than one person per 2000 in the general population or affecting less than 200 000 people in the US population.2,3 The name of the disease originates from the initials of the three authors, Miller, McKusick and Malvaux, who first reported the syndrome in the literature.4 There is a lack of information about anaesthesia in children with 3M syndrome. Having obtained parental consent, we report this case in an attempt to contribute to knowledge about anaesthesia in children with rare diseases.5,6

A 6-year-old boy, who was admitted to the hospital to undergo inguinal hernia repair, was referred for anaesthetic review. He was a short boy, weighing 11.5 kg, with facial dysmorphism, namely a triangular face, broad head and pointed chin. According to the history, he and his twin brother, who had the same facial characteristics and dwarfism, were born in the 32nd week of pregnancy by caesarean section. At that time, our patient weighed 746 g and was admitted for 10 days to the neonatal intensive care unit for mild respiratory insufficiency. No other data about the immediate postnatal period were available, because the child was not born in our country. His mother was a short lady with a height of 143 cm, who claimed to have been investigated as a child for dwarfism.

When our patient was 2 years of age, he was admitted to the Paediatric Department for investigation of growth retardation. At that time, he was below the 3rd percentile for weight and height. Thyroid function and the rest of the endocrine evaluation were normal. Genetic consultation diagnosed 3M syndrome. A hypercaloric diet was recommended.

In addition, he had a solitary kidney and normal cystography. Evaluation of kidney function with 99-Technetium dimercaptosuccinic acid revealed a normally functioning right kidney and a small, dysmorphic left kidney without functional involvement (0.1%). He was routinely re-evaluated by a nephrologist for this dysfunction.

During the preanaesthetic assessment, a review of his past records was undertaken. As the syndrome belongs to the rare diseases, we asked for a cardiologist's consultation, although the syndrome is not characterised by cardiac dysfunction. Cardiac auscultation revealed a systolic (1/6), innocent murmur. Echo and ECG showed no cardiac abnormalities. Biochemistry was completely normal despite kidney dysfunction, and blood pressure (BP) monitoring did not show any abnormalities. He had no history of chronic respiratory problems or recent respiratory infection. He appeared to have speech retardation and his movements were slow, but his intelligence was normal. He had a Mallampati class 1 airway, normal mouth opening and sufficient neck movement, while the thyromental distance was 6 cm.

On the day of surgery, he was premedicated with midazolam 0.3 mg kg−1 p.o. Monitoring consisted of ECG, non-invasive BP, pulse oximetry and capnography. During induction of anaesthesia, propofol 3 mg kg−1, fentanyl 2 μg kg−1 and rocuronium 1 mg kg−1 were administered. At laryngoscopy, a Cormack and Lehane grade 1 view was obtained and intubation was easily performed with a 5.5 mm endotracheal tube. Maintenance of anaesthesia was achieved with sevoflurane in oxygen and air, and a continuous infusion of remifentanil. The rate of infusion was determined by heart rate and BP. Ondasetron 0.1 mg kg−1 and dexamethasone 0.2 mg kg−1 were the antiemetic agents given, and paracetamol 15 mg kg−1 intravenously in addition to local infiltration of the wound with ropivacaine was administered for postoperative analgesia. Haemodynamic and respiratory parameters remained within normal limits. At the end of surgery, neuromuscular blockade was reversed with neostigmine and atropine and the patient was extubated. Postanaesthesia care was uneventful and the patient left the hospital later the same day.

3M syndrome is a rare disease with fewer than 100 patients having been reported in the medical literature since 1975.7 It belongs to the proportionate type of dwarfism, characterised by proportional but severely delayed growth, a process that begins in the uterus. It is a primordial growth disorder resulting in an adult height of 115 to 150 cm.8

Prenatal and postnatal retardation is accompanied by specific facial and skeletal features and normal intelligence.1 Analytically, facial characteristics such as a triangular face, full eyebrows, hypoplastic midface, fleshy nose tip, upturned nares, long philtrum, prominent mouth and lips and pointed chin, are present. Head circumference often remains within the normal range, and in association with the prominent forehead, the impression of a disproportionately large head in comparison to body size is given.9 Skeletal anomalies consist of prominent trapezii, short broad neck, deformed sternum, short thorax, square shoulders, winged scapulae, short 5th fingers, prominent heels, hyperlordosis and loose joints (dislocated hips).10 Radiographic evidence of the disease includes slender long bones with diaphyseal constriction and flared metaphyses, tall vertebral bodies with reduced anterior-posterior and transverse diameter, anterior wedging of thoracic vertebral bodies, broad thorax with slender and horizontal ribs, thoracic kyphoscoliosis, small iliac wings and spina bifida occulta. These findings are prominent after the second year of life.7,10 Hypergonadotropic hypogonadism has been reported in boys with 3M syndrome. Testicles are small for pubertal size and oligo-azoospermia exists. A few boys have hypospadias, although the rest of the endocrine function is normal.10 Females usually have normal gonadal function, although both sexes are equally affected by the syndrome.11 The usual indication for surgery is bone lengthening.7 Medical treatment with growth hormone, though usually administered, does not seem to be efficient.1,7

The disease is caused by mutations in Cullin 7 (CUL7) gene on chromosome 6p21.1, accounting for 70% of cases, or in the Obscurin-like 1 (OBSL1) gene on chromosome 2q35–36.1 encoding a cytoskeletal adaptor protein.8,12 Absence of these mutations in 6% of the families tested may suggest the involvement of a third gene.1

Regarding anaesthesia in adult patients with 3M syndrome, there is only one case of a lady undergoing emergency caesarean section reported.13 She had undergone several orthopaedic operations at a young age with no anaesthetic complications. When she underwent caesarean section at age 33, she had a Cormack and Lehane grade 3 view laryngoscopy and the trachea was intubated with a 6 mm endotacheal tube using a bougie. A conclusion cannot be made as to whether the intubation difficulty relates to the progression of the syndrome, to the pregnancy or to the combination of both.13

The experience from our patient makes us believe that anaesthesia in children with 3M syndrome is safe and is not connected to specific complications. The disease does not affect the respiratory, cardiac, endocrine or neuromuscular systems. Furthermore, the origin of the disorder precludes an effect on the metabolism of anaesthetic drugs, a fact that could lead to the preference of any specific anaesthetic technique, namely inhalational, total intravenous or regional.

However, it seems that intubation difficulties may arise at a later age, probably because of the progression of skeletal and facial abnormalities. The short neck, short vertebral column, kyphoscoliosis, midface and maxillary hypoplasia, prominent mouth, etc. are features that may accentuate difficulty in laryngoscopy and intubation during general anaesthesia or performance of regional techniques during regional anaesthesia in adulthood. Although the review of the literature supports the lack of specific anaesthetic implications of 3M syndrome, we believe that the preanaesthetic review should be thorough and should investigate the possible presence of other co-existing problems. In our case, kidney function was evaluated, due to the additional nephrological abnormality. The report of a sufficient (for an orphan disease) number of cases could lead to permanent conclusions about anaesthesia and children with 3M syndrome.

Acknowledgements

Assistance with the letter: none declared.

Financial support and sponsorship: none declared.

Conflicts of interest: none declared.

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© 2012 European Society of Anaesthesiology