[MIM 246 200]

(Donohue syndrome)

Very rare. Severe congenital insulin resistance. Autosomal recessive transmission of a mutation of the INSR gene (on 9p13.2) coding for the insulin receptor.

Clinical presentation:

-        intrauterine and postnatal growth retardation with hyperinsulinism and episodes of  hypo- or hyperglycemia (after meals): muscle atrophy, lipoatrophy, thick skin, intrahepatic cholestasis

-        hyperandrogenism: polycystic ovary syndrome, gynecomastia, macropenis or hypertophy of the clitoris

-        excessive growth of some organs: hypertrophic cardiomyopathy, hepatomegaly, splenomegaly

-        typical facies: elfin facies (leprechaun = gnome of irish folklore) with broad forehead, wide palpebral fissures, a nose with a bulbous tip, anteverted nostrils, an arched palate, a large mouth and low implanted large ears.

Generally, early death in the first year of life.

Still experimental treatment: continuous subcutaneous injection of recombinant IGF - 1 (insulin-like growth factor 1) which seems to restore glucose metabolism and decrease insulin levels.

Anesthetic implications:

preoperative echocardiography; check blood glucose, liver function and hemostasis; hypotrophic patient with abdominal distension; risk of difficult mask ventilation (reduced thoracic compliance); risk of aspiration pneumonitis: (advice:  cricoid pressure and continuous suction on the gastric tube or gastrostomy for the time of mask ventilation); management of a cardiomyopathy.

References :

-        Planchenault D, Martin-Coignard D, Rugemintwaza D, Bah A-G et al. 
Le syndrome de Donohue ou lepréchaunisme : à propos d’un cas. 
Arch Pédiatr 2014 ; 21 :  206-10.

-        de Bock M, Hayes I, Semple R. 
Donohue syndrome. 
J Clin Endocrinol Metab 2012 ; 97 : 1416-7.

-        Leprechaunism (Donohue syndrome) : report of a case in a neonate. 
Koklu E, Ariguloglu AE, Koklu S. 
J Pediatr Endocr Metab 2014, 27:207-8

-        Weber DR, Stanescu DE, Semple R, et al.
Continuous subcutaneous IGF-1 therapy via insulin pump in a patient with Donohue syndrome.
J Pediatr Endocrinol Metab 2014; 27:1237–41

-        Termote JUM, Breur JMPJ, de Vroede MAMJ. Hypertrophic cardiomyopathy in Donohue syndrome. Cardiology in the Young 2016; 26: 815-8

-        Kirkwood A, Stuart G, Harding L.
Donohue syndrome: a review of literature, case series, and anesthetic considerations.
Pediatr Anesth 2018; 28:23-7

Updated: December 2017