title: Facial appearance in persistent hyperinsulinemic hypoglycemia.
abstract: Persistent hyperinsulinism is the most common cause of recurrent hypoglycemia in infancy because of inappropriate oversecretion of insulin by the pancreas. Pancreatic lesions can be either focal or diffuse, and they have distinct molecular bases. We have studied the facial features in 17 unrelated patients presenting with neonatal (n = 8) or infancy-onset (n = 9) hyperinsulinism. Hyperinsulinism was related to focal adenomatous hyperplasia (n = 7), diffuse hyperinsulinism (n = 5), non-operated hyperinsulinism (n = 2), and hyperinsulinism with hyperammonemia (n = 3). SUR1 or Kir6.2 mutations were found in six of seven focal adenomatous hyperplasia and three of five diffuse hyperinsulinism. A loss of the maternal allele from chromosome 11p15 in the lesion was found in all focal adenomatous hyperplasia. GLUD1 mutations were found in all patients with hyperammonemia. Large birth weight (mean > 3,800 g) was consistently observed (11/17) but protruding tongue, exomphalos, or visceromegaly were never noted and Wiedemann-Beckwith syndrome could always be ruled out. All patients presented with high forehead, small nasal tip, and short columella giving the impression that the nose is large and bulbous, smooth philtrum, and thin upper lip. A square appearance to the face was more obvious in younger patients. These specific facial features, observed in patients with hyperinsulinism of various molecular mechanisms, could be the consequence of fetal intoxication by insulin. However, to date, facial anomalies have not been noted in infants of diabetic mothers and inversely, malformations that are commonly reported in infants of diabetic mothers were not present in our hyperinsulinemic patients.
authors.affiliation: Département de Pédiatrie, INSERM-U383, Hôpital Necker-Enfants Malades, Paris, France. pascale.de-lonlay@necker.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Guy
authors.initials: G
authors.lastname: Touati
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Fournet
authors.forename: Francis
authors.initials: F
authors.lastname: Brunelle
authors.forename: Claire
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: Jacques
authors.initials: J
authors.lastname: Rahier
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Robert
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D018528:ATP-Binding Cassette Transporters; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005147:Facial Bones / Q000002:abnormalities*; D020558:GTP Phosphohydrolases / Q000235:genetics; D005969:Glutamate Dehydrogenase / Q000235:genetics; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications* / Q000235:genetics; D007003:Hypoglycemia / Q000209:etiology*; D017874:Immediate-Early Proteins / Q000235:genetics; D007223:Infant; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D020558:GTP Phosphohydrolases; D005969:Glutamate Dehydrogenase; D017874:Immediate-Early Proteins; D020559:Monomeric GTP-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C577507:ABCC8 protein, human; C490245:GEM protein, human