Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing's syndrome and acral cutaneous mucinosis

Sinéad M McGlacken-Byrne; Ashraf Abdelmaksoud; Mohammad Haini; Liina Palm; Michael Ashworth; Juan Li; Wei Wang; Xiumin Wang; Jian Wang; Bridget Callaghan; Veronica A Kinsler; Francesca Faravelli; Mehul T Dattani

doi:10.1530/EJE-22-0287

Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing's syndrome and acral cutaneous mucinosis

Eur J Endocrinol. 2022 Dec 1;187(6):K55-K61. doi: 10.1530/EJE-22-0287.

Authors

Sinéad M McGlacken-Byrne^{1

2}, Ashraf Abdelmaksoud³, Mohammad Haini⁴, Liina Palm⁴, Michael Ashworth⁴, Juan Li⁵, Wei Wang⁶, Xiumin Wang⁵, Jian Wang⁷, Bridget Callaghan³, Veronica A Kinsler^{2

8

9}, Francesca Faravelli¹⁰, Mehul T Dattani^{1

2}

Affiliations

¹ Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK.
² Genetics and Genomic Medicine Programme, UCL GOS Institute of Child Health, London, UK.
³ International and Private Patient Department, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
⁴ Department of Histopathology, Great Ormond Street Hospital for Children, London, UK.
⁵ Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁶ Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁷ Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁸ Department of Dermatology, Great Ormond Street Hospital for Children, London, UK.
⁹ Mosaicism and Precision Medicine Laboratory, Francis Crick Institute, London, UK.
¹⁰ North East Thames Regional Genetic Service, Great Ormond Street Hospital, London, UK.

PMID: 36691942
DOI: 10.1530/EJE-22-0287

Abstract

We describe a mosaic PRKACA duplication in a young infant who presented with a Carney-like complex: bilateral non-pigmented micronodular adrenal hyperplasia, severe early-onset Cushing's syndrome, and distinct acral soft tissue overgrowth due to cutaneous mucinosis. This represents a novel manifestation of PRKACA disruption and broadens the extra-adrenal phenotype of PRKACA-associated Cushing's syndrome. Our data suggest that Cushing's syndrome phenotypes arising from somatic and germline PRKACA abnormalities can exist on a spectrum. We emphasise the value of ascertaining a genetic diagnosis for PRKACA-mediated adrenal and extra-adrenal disease to guide individualised and targeted care.

Publication types

Case Reports

MeSH terms

Adrenal Hyperplasia, Congenital* / genetics
Cushing Syndrome* / diagnosis
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics
Humans
Infant
Mucinoses* / complications
Phenotype

Substances

Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
PRKACA protein, human