Ongoing challenges in the diagnosis of 11p15.5-associated imprinting disorders
Ongoing challenges in the diagnosis of 11p15.5-associated imprinting disorders
The overgrowth disorder Beckwith–Wiedemann syndrome and the growth restriction disorder Silver–Russell syndrome have been described as ‘mirror’ syndromes, in both their clinical features and molecular causes. Clinically, their nonspecific features, focused around continuous variables of atypical growth, make it hard to set diagnostic thresholds that are pragmatic without potentially excluding some cases. Molecularly, both are imprinting disorders, classically associated with ‘opposite’ genetic and epigenetic changes to genes on chromosome 11p15, but both are associated with somatic mosaicism as well as an increasing range of alternative (epi)genetic changes to other genes, which make molecular diagnosis an increasingly complex process. In this Current Opinion, we explore how the understanding of Beckwith–Wiedemann syndrome and Silver–Russell syndrome has evolved in recent years, stretching the canonical ‘mirror’ designations in different ways for the two disorders and how this is changing clinical and molecular diagnosis. We suggest some possible directions of travel toward more timely and stratified diagnosis, so that patients can access the early interventions that are so critical for good outcome.
263-272
Mackay, Deborah J. G.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
6 May 2022
Mackay, Deborah J. G.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Mackay, Deborah J. G. and Temple, I. Karen
(2022)
Ongoing challenges in the diagnosis of 11p15.5-associated imprinting disorders.
Molecular Diagnosis & Therapy, 26 (3), .
(doi:10.1007/s40291-022-00587-1).
Abstract
The overgrowth disorder Beckwith–Wiedemann syndrome and the growth restriction disorder Silver–Russell syndrome have been described as ‘mirror’ syndromes, in both their clinical features and molecular causes. Clinically, their nonspecific features, focused around continuous variables of atypical growth, make it hard to set diagnostic thresholds that are pragmatic without potentially excluding some cases. Molecularly, both are imprinting disorders, classically associated with ‘opposite’ genetic and epigenetic changes to genes on chromosome 11p15, but both are associated with somatic mosaicism as well as an increasing range of alternative (epi)genetic changes to other genes, which make molecular diagnosis an increasingly complex process. In this Current Opinion, we explore how the understanding of Beckwith–Wiedemann syndrome and Silver–Russell syndrome has evolved in recent years, stretching the canonical ‘mirror’ designations in different ways for the two disorders and how this is changing clinical and molecular diagnosis. We suggest some possible directions of travel toward more timely and stratified diagnosis, so that patients can access the early interventions that are so critical for good outcome.
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Accepted/In Press date: 3 April 2022
e-pub ahead of print date: 6 May 2022
Published date: 6 May 2022
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Funding Information:
IKT is supported by the National Institutes of Health Research Biomedical Research Centre, Southampton.
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© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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Local EPrints ID: 457515
URI: http://eprints.soton.ac.uk/id/eprint/457515
ISSN: 1177-1062
PURE UUID: a2a0e72d-600d-4178-b181-83ae0f5aa54c
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Date deposited: 09 Jun 2022 17:34
Last modified: 17 Mar 2024 07:18
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