Journal Article

Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype–phenotype correlation in an international cohort of patients

Shield, J. P. H., Kabwama, S., Lehmann, A., Hawke, E., Flanagan, S. E., Hattersley, A. T., Mackay, D. J. G., Harrison, L., Ennis, S., Docherty, L. E., Ellard, S., Temple, I. K.

2013

Overview

Aims/hypothesis 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/interpretation 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.

• Publisher: Springer-Verlag,Springer
• Subject: Abnormalities, Multiple - genetics / Age of Onset / Biological and medical sciences / Chromosomes, Human, Pair 6 / Cohort Studies / Diabetes Mellitus - diagnosis / Diabetes Mellitus - genetics / Diabetes. Impaired glucose tolerance / DNA Methylation / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Genetic Association Studies / Genomic Imprinting / Genotype / Gestational Age / Human Physiology / Humans / Infant, Newborn / Infant, Newborn, Diseases - genetics / Internal Medicine / Male / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Phenotype / Remission Induction / Uniparental Disomy - genetics