ESPE Abstracts (2021) 94 S12.1

Professor of Medical Genetics, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. Honorary Consultant in Clinical Genetics, University Hospital Southampton, Southampton, United Kingdom


Human imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of gene dosage at imprinted loci across the genome. Causes of disease include point mutations, structural variants, uniparental disomy and ‘epimutations’ with a parent of origin specific effect. Further complexity underlies the causes of the epigenomic errors that may be the result of genetic and environmental factors at different times during the development of the oocyte, the sperm and the early embryo. The diagnosis of these disorders is important to optimise growth, prevent long-term metabolic disturbance and childhood cancers. Imprinting disorders are likely underdiagnosed resulting in a group of patients offered suboptimal treatment. Causes include: -

1. many of the clinical features of imprinting disorders are non-specific and change with age making diagnosis difficult

2. heterogeneity and clinical overlap between conditions requires a broad diagnostic approach across many imprinted loci

3. standard diagnostic pathways that focus on genomic sequencing do not identify a significant proportion of molecular mechanisms underlying imprinting disorders

4. multi-locus imprinting disturbance (MLID) may affect the phenotype which can range from early miscarriage to less classical non-specific developmental delay and yet is not tested for routinely in most labs

5. diagnostic genomic sequencing focuses on the patient and not the mother. Maternal mutations in a key network of oocyte-expressed genes can result in MLID in their offspring who do not share the mutations.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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