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Anaesthesia and orphan disease

A child with Congenital Cataract Facial Dysmorphism neuropathy (CCFDN) syndrome

a case report

Masters, Oliver W.; Bergmans, Elonka; Thies, Karl-Christian

Author Information
European Journal of Anaesthesiology: March 2017 - Volume 34 - Issue 3 - p 178-180
doi: 10.1097/EJA.0000000000000586
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Editor,

We report the case of a 9-year-old boy of Romanian origin with congenital cataract facial dysmorphism neuropathy (CCFDN) syndrome who presented for tibialis tendon transfer and bilateral orchidopexy. CCFDN syndrome is an extremely rare inherited condition, prevalent in Roma. CCFDN syndrome is associated with acute rhabdomyolysis and seemingly has a high incidence of anaesthetic complications.1 CCFDN syndrome has also repeatedly been reported to be associated with malignant hyperthermia.2–6, but we could not find any evidence to support this. To date, there are no comprehensive case reports of these children undergoing anaesthesia.

Case report

Written informed consent for publication was obtained from the patient's mother. The boy was born at full term via a normal vaginal delivery and was initially well at birth. At 14 days of life, his mother noted that he was visually inattentive and he was found to have congenital cataracts and micro-ophthalmia by the ophthalmologists in Prague. At 2 months of age, he had surgery on his right eye, which was subsequently re-operated on at 6 months of age. Details of this anaesthetic were not available but the mother reported that it was uneventful. The patient's development was delayed – sitting at 1 year and walking by 28 months – but extensive investigation failed to elucidate a diagnosis. At 33 months, after a febrile episode, the boy became very unwell and presented with profound muscle weakness and rhabdomyolysis. The initial diagnosis was Guillain Barré syndrome but further investigations revealed the diagnosis of CCFDN syndrome.

On presentation to our service, the patient weighed 24 kg and was 9-years old. He could walk, but with a limp, and dress himself with help. For his age, his speech was good and he could converse fluently in his mother tongue. He had significant visual impairment, nystagmus and microcephaly. He was globally hypotonic, had absent ankle reflexes, and he also had a marked valgus deformity of his right foot. No bulbar problems were identified and he could eat and drink normally without assistance. Mild facial dysmorphia was noted with typically prominent upper incisors. Cardiovascular examination, including an echocardiogram and ECG, was normal.

Because of the risk of rhabodomyolysis, we opted for a total intravenous anaesthetic. Anaesthesia was induced and maintained with a propofol and remifentanil infusion. A size 2.5 laryngeal mask airway and a nasal temperature probe were inserted. Bilateral ilio-inguinal blocks and a right-sided ultrasound-guided popliteal block were placed. A total of 1 ml kg−1 of 0.25% levobupivacaine was used. The procedure itself took just over 90 min and the patient remained stable throughout. Postoperatively, he was comfortable and alert in the postanaesthesia care unit and did not require any supplemental analgesia. As a precaution, he was discharged to the paediatric intensive care unit (PICU) where he remained under observation for 12 h. His observations remained normal and his urine was free of myoblobin. He was discharged back to the ward the following morning and discharged home 5 days later.

Discussion

CCFDN syndrome is a complex developmental disorder, affecting patients of Roma ethnicity. The condition is caused by a mutation in the CTDP1 gene on chromosome 18 and is inherited in an autosomal recessive manner.2 There are over 100 patients who have been diagnosed with CCFDN syndrome. Patients often present in early infancy with bilateral congenital cataracts. Other ophthalmic signs include microcorneae, microphthalmos and micropupils, with strabismus and horizontal nystagmus.1 Patients tend to be of small stature and low weight although these were not features of our patient. Facial dysmorphism develops late in childhood causing a prominent mid-face, forward pointing incisors and thickening of peri-oral tissues with micrognathia. Although these are features that may be expected to increase the likelihood of difficult laryngoscopy, this is not a feature described in the literature. Skeletal deformities are present in most patients and include foot and hand deformities as well as kyphoscoliosis. The latter may result in restrictive respiratory problems.

The most obvious neurological manifestation is a symmetrical distal peripheral neuropathy, primarily affecting the motor neurons. Nerve biopsy is likely to reveal evidence of primary hypomyelination. Other neurological features may include choreiform movements, epileptic seizures and an upper limb postural tremor as well as mild intellectual impairment. Patients suffering from CCFDN syndrome also demonstrate a susceptibility to rhabdomyolysis on exposure to environmental factors such as viral infection.2–6

Patients may present to anaesthesiologists because they require ophthalmic procedures or correction of skeletal or gonadal abnormalities. Furthermore they can present during a episode of rhabdomyolysis requiring admission to the intensive care. An ophthalmologic case series reported anaesthesia-related complications in four out of nine children; these patients suffered pulmonary oedema, epileptic seizures or severe inspiratory stridor leading to postoperative PICU admission.1 Unfortunately, the authors do not provide any further information on the anaesthetic techniques or the nature and the outcome of these incidents.

As regards the anaesthetic implications of CCFDN, we suggest the following:

  1. Given the high risk of rhabdomyolysis exposure to volatile anaesthetics should be limited and depolarising muscle relaxants should be avoided. Depolarising muscle relaxants may also trigger hyperkalemia in the presence of demyelinating neuropathy. To control patient stressors, particular attention should be paid to good postoperative pain control. Myoglobin levels should be monitored postoperatively.
  2. Nondepolarising muscle relaxants should be used with caution because of the muscle hypotonia. If muscle relaxants are required, neuro-muscular monitoring should be used, with baseline recordings obtained before the muscle relaxant is administered. Facial neuromuscular monitoring may be preferable, as nerves here are possibly least affected by the underlying polyneuropathy. We feel that rocuronium would be an appropriate choice of muscle relaxant because it allows complete reversal with sugammadex at the end of the procedure.
  3. Although the significant facial dysmorphism should alert one towards the possibility of a potentially difficult airway, such a problem has not been described in the literature.
  4. Kyphoscoliosis may result in significant respiratory embarrassment, especially if combined with muscle weakness. This is an important consideration during the pre-operative assessment as there may be a need for a period of postoperative ventilatory support.
  5. The descriptions of CCFDN syndrome and the case series we have found in the literature do not indicate any cardiac or pulmonary disease; however, one patient reportedly suffered postoperative pulmonary oedema. Therefore, preanaesthesia assessment should also focus on detecting co-existing cardiopulmonary disorders.
  6. The presence of osteoporosis means that extra care should be taken during the manual handling of these patients because of the potential for iatrogenic fractures.
  7. The frequent incidence of rhabdomyolysis has apparently been interpreted as possible malignant hyperthermia susceptibility. However, our literature search has not revealed any reasonable evidence to support this assumption. Given the different gene localisations of malignant hyperthermia and CCFDN syndrome and the different inheritance patterns, any association would also be extremely unlikely. CCFDN syndrome patients therefore should not be labelled as being malignant hyperthermia susceptible.

CCFDN is a rare, complex congenital disorder and affected patients will almost inevitably require surgery at some stage of childhood. Anaesthesia in CCFDN carries increased risks, especially the risk of rhabdomyolysis, but CCFDN does not appear to be related to malignant hyperthermia.

Acknowledgements relating to this article

Assistance with the case report: none.

Financial support and sponsorship: none.

Conflicts of interest: none.

References

1. Mullner-Eidenbock A, Moser E, Klebermass N, et al. Ocular features of the congenital cataracts facial dysmorphism neuropathy syndrome. Ophthalmology 2004; 111:1415–1423.
2. Merlini L, Gooding R, Lochmüller H, et al. Genetic identity of Marinesco-Sjogren/myoglobinuria and CCFDN syndromes. Neurology 2002; 58:231–236.
3. Kalaydjieva L, Chamova T. Congenital Cataracts, Facial Dysmorphism, and Neuropathy (2014). https://www.ncbi.nlm.nih.gov/books/NBK25565/?report=reader [Accessed 10 November 2016]
4. Angelicheva D, Turnev I, Dye D, et al. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. Eur J Hum Genet 1999; 7:560–566.
5. Kalaydjieva L. Congenital cataracts-facial dysmorphism-neuropathy. Orphanet J Rare Dis 2006; 1:32.
6. Lassuthova P, Sišková D, Haberlová J, et al. Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) in 10 Czech Gypsy children: frequent and underestimated cause of disability among Czech Gypsies. Orphanet J Rare Dis 2014; 9:46.
© 2017 European Society of Anaesthesiology