[MIM 223 900]

(Riley-Day syndrome, congenital insensitivity to pain of type III, HSAN III)

Especially in people of Ashkenazi descent. Autosomal recessive transmission of a mutation of the IKBKAP gene on l9q31 resulting in a loss of myelinated Aâ and Aä fibres, and a severe involvement of the C fibers. In addition, MAOI A tissue concentrations are low. There is an autonomic dysfunction associated with a diffuse loss of tact and nociception but the perception of visceral and musculoskeletal pain is normal. Responses to hypoxemia and the hypercarbia are very reduced.

Onset in the neonatal period with difficulties in feeding, episodes of fever, increased sweating (risk of hypoNa).

One can observe:

-        orthostatic hypotension without compensatory tachycardia and hypertension in the supine position;

-        painless sores;

-        absence of tears;

-        digestive dysmotility: gastroesophageal reflux, gastric emptying delay, dysphagia and esophageal dysmotility with aspiration pneumonia which are an indication for a of percutaneous gastrostomy; excessive salivation.

-        obstructive sleep apnea is a frequent cause of death as hypoxemia does not awaken the patient: these children are therefore often equipped with a CPAP or BiPaP during nightime

-        chronic renal failure is often present: sequelae of hypertensive crises or denervation of renal arteries?

-        orthopedics: osteopenia with increased risk of fracture. ataxic gait; scoliosis with or without kyphosis; Charcot deformation of large joints (as a result of repeated non painful trauma), sometimes rhabdomyolysis due to prolonged immobilization.

-        occasional hyperthermic seizures, hyponatremia or apnea and hypoxemia.

-        a long QT during exercise is observed in 1/3 of cases.

-        dysautonomic crisis  [hypertension with efforts of vomiting or tachycardia, excessive salivation, mydriasis, sweating, skin rash] can be induced by stress or adopting the supine position: they are due to the absence of baroreflex when a sympathetic discharge occurs in the body, and to the decreased metabolism of noradrenaline and dopamine the blood levels of which remain high; vomiting is due to stimulation of the dopamine receptors D2 and D3 at the level of the area postrema. Treatment with IV diazepam or clonidine IV or by patch (0.1 to 0.3 mg/24 h).

A long-term treatment with large doses of vitamin E (tocotrienols) and green tea extracts (Epigallocatechin-3-gallate) derivatives can restore normal levels of IKAP protein and thus of tissular MAOI, thereby reducing the crises of dysautonomia (hypertension, skin flush, sweating). This treatment (which interferes in vitro with platelet function tests) must therefore be pursued in perioperative period.

Treatment with carbidopa (dopa-decarboxylase inhibitor) can also reduce the frequency of the dysautonomic crises.

Anesthetic implications: 

-        see: hemoglobin (chronic anemia?) and renal function; ECG: long QT ?

-        nocturnal non-invasive CPAP or BiPAP ventilation ?

-        although classically contraindicated (risk of hyperthermia ?), the administration of atropine or glycopyrrolate does not involve any deleterious effects.

-        anxiety can cause a dysautonomic crisis: effective premedication or the presence of parents is therefore useful during induction of anesthesia.

- risk of pulmonary aspiration of gastric contents: dysmotility of the esophagus, delayed gastric emptying. Rapid sequence induction ?

-        chronic subclinical hypovolemia (dehydration + dysphagia) is frequently present: the administration of preoperative IV infusion is therefore useful to avoid hypotension after induction

-        painful stimuli do not produce a hemodynamic response: so it's useful to use BIS (or another way to measure the depth of anesthesia) to titrate the dose of  IV anesthetics or halogenated agents.

-        cases of major hypotension and even cardiac arrests were reported long ago: it has not been confirmer whether those data remain current with sevoflurane

-        exaggerated blood pressure response to noradrenaline; prefer phenylephrine (0.5 to 1 µg/kg) in case of hypotension

-        in case of hypertension: clonidine 0.5 to 1µg/kg

-        in case of tachycardia: esmolol 25-100 µg/kg

-        perimedullar regional anesthesia has been used with success despite the kyphoscoliosis

-        tramadol is probably not a good choice as an analgesic as serotonin metabolism can be modified by a decreased tissue level A MAOI

-        avoid the setrons as antiemetics as serotonin metabolism can be modified by decreased tissue level MAOI A

-        the response to hypoxia and hypercarbia is diminished: significant risk for slow awakening and apnea; pre- and post-operative physiotherapy to prevent pulmonary complications

-        eye protection because lack of tears and insensitivity of the cornea

-        a case of combined use of propofol (100-150 µg/kg/min) and dexmedetomidine (0.7 µg/kg/h) has been reported

-        to avoid high blood pressure while lying supine in the post-operative period: put the bed in anti-Trendelenburg of 30 ° or put the patient in the semi-sitting position as soon as possible

References : 

-         Challans JF, Facer EK. 
Epidural anaesthesia and familial dysautonomia (Riley-Day syndrome). Three case reports. 
Paediatr Anaesth 1998; 8: 83-8.

-         Ngai J, Kreynin I, Kim JT, Axelrod FB. 
Anesthesia management of familial dysautonomia. 
Pediatr Anesth 2006; 16: 611-20.

-         Adhikary SD, Korula PJ. 
The role of monitoring the depth of anesthesia in a case of hereditary sensory and autonomic neuropathy (Riley-Day syndrome). 
Pediatr Anesth 2007; 17: 402-3.

-         Weingarten TN, Sprung J, Burgher AH. 
Perioperative management of familial dysautonomia: a systematic review. 
Eur J Anesthesiol 2007; 24: 309-16.

-         Ahmed N, Watve MM, Ahmed M. 
Spinal anesthesia in Riley-Day syndrome (familial dysautonomia). 
Pediatr Anesth 2008; 18: 1136-7

-         Abulhasan Y, Buu N, Frigon C. 
Perioperative use of dexmedetomidine in an infant with familial dysautonomia. 
Br J Anaesth 2009; 103: 413-5.

-         Cook-Sather SD, Viola L, Zur KB, Rubin BY. 
Case scenario: perioperative administration of tocotrienols and green tea extract in a child with familial dysautonomia. 
Anesthesiology 2012; 117: 639-45.

-         Palma J-A, Norcliffe-Kautmann L, Fuente-Mora C, Percival L, Mendoza-Santiesteban C, Kaufmann H. 
Current treatments in familial dysautonomia.  
Expert Opin Pharmacother 2014 ; 15 : 2653-71

-        Milne A, Mon WY, Down J, Obichere A, Ackland GL.
Contemporary perioperative management of adult familial dysautonomia (Riley-Day syndrome).
A & A Case Reports 2015; 4:111-3.        

Updated: August 2019