A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

Benjamin Kamien; Anne Ronan; Gemma Poke; Ingrid Sinnerbrink; Gareth Baynam; Michelle Ward; William T Gibson; Tracy Dudding-Byth; Rodney J Scott

doi:10.1159/000484532

A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

Mol Syndromol. 2018 Feb;9(2):70-82. doi: 10.1159/000484532. Epub 2018 Jan 25.

Authors

Benjamin Kamien^{1

2

3}, Anne Ronan^{1

2}, Gemma Poke⁴, Ingrid Sinnerbrink^{5

6}, Gareth Baynam^{7

8

9

10

11

12

13}, Michelle Ward⁷, William T Gibson^{14

15}, Tracy Dudding-Byth^{1

16

2

17}, Rodney J Scott^{3

18}

Affiliations

¹ Hunter Genetics, Perth, WA, Australia.
² School of Medicine and Public Health, The University of Newcastle, Perth, WA, Australia.
³ School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle, NSW, Australia.
⁴ Department of Clinical Genetics, Capital & Coast District Health Board, Wellington, New Zealand.
⁵ Department of Clinical Genetics, Nepean Hospital, Perth, WA, Australia.
⁶ Nepean Clinical School, University of Sydney, Penrith, NSW, Australia.
⁷ Genetic Services of Western Australia, Newcastle, NSW, Australia.
⁸ Western Australian Register of Developmental Anomalies, Perth, WA, Australia.
⁹ Office of Population Health Genomics, Public Health Division, Department of Health, Government of Western Australia, Perth, WA, Australia.
¹⁰ School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
¹¹ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
¹² Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
¹³ Spatial Sciences, Department of Science and Engineering, Curtin University, Perth, WA, Australia.
¹⁴ Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
¹⁵ BC Children's Hospital Research Institute, Vancouver, BC, Canada.
¹⁶ GrowUpWell Priority Research Center, Perth, WA, Australia.
¹⁷ Hunter Medical Research Institute, Perth, WA, Australia.
¹⁸ Molecular Pathology, Hunter Area Pathology Service, Perth, WA, Australia.

Abstract

The overgrowth syndromes are important to diagnose, not just for accurate genetic counseling, but also for knowledge surrounding cancer surveillance and prognosis. There has been a recent expansion in the number of genes associated with a mendelian overgrowth phenotype, so this review updates previous classifications of overgrowth syndromes. We also describe a clinical and molecular approach to the investigation of individuals presenting with overgrowth. This review aims to assist the clinical diagnosis of generalized overgrowth syndromes by outlining the salient features of well-known overgrowth syndromes alongside the many syndromes that have been discovered and classified more recently. We provide key clinical "handles" to aid clinical diagnosis and a list of genes to aid with panel design when using next generation sequencing, which we believe is frequently needed due to the overlapping phenotypic features seen between overgrowth syndromes.

Keywords: Large stature; Macrocephaly; Macrosomia; Obesity; Overgrowth; Tall stature.

Publication types

Review