title: Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients.
abstract: OBJECTIVE
  6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups.
  
  
  METHODS
  One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients.
  
  
  RESULTS
  6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%.
  
  
  CONCLUSIONS
  This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.
authors: Faculty of Medicine, University of Southampton, Mailpoint 105, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK.
authors: L E
authors: LE
authors: Docherty
authors: S
authors: S
authors: Kabwama
authors: A
authors: A
authors: Lehmann
authors: E
authors: E
authors: Hawke
authors: L
authors: L
authors: Harrison
authors: S E
authors: SE
authors: Flanagan
authors: S
authors: S
authors: Ellard
authors: A T
authors: AT
authors: Hattersley
authors: J P H
authors: JP
authors: Shield
authors: S
authors: S
authors: Ennis
authors: D J G
authors: DJ
authors: Mackay
authors: I K
authors: IK
authors: Temple
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D017668:Age of Onset; D002896:Chromosomes, Human, Pair 6; D015331:Cohort Studies; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018392:Genomic Imprinting; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics; D008297:Male; D010641:Phenotype; D012074:Remission Induction; D024182:Uniparental Disomy / Q000235:genetics
references: Diabetes. 2007 Jul;56(7):1930-7
references: 17446535
references: Hum Genet. 2006 Sep;120(2):262-9
references: 16816970
references: Orphanet J Rare Dis. 2007 Mar 09;2:12
references: 17349054
references: Diabetes. 2000 Aug;49(8):1359-66
references: 10923638
references: Nat Genet. 2008 Aug;40(8):949-51
references: 18622393
references: Pediatr Diabetes. 2012 Mar;13(2):155-62
references: 21518169
references: Hum Reprod. 2008 Dec;23(12):2826-34
references: 18703582
references: Hum Genet. 2005 Mar;116(4):255-61
references: 15635480
references: J Pediatr. 2002 Oct;141(4):483-9
references: 12378186