Expanding the phenotypic spectrum of Kenny-Caffey syndrome: a case series and systematic literature review

Schigt, H. et al. (2023) Expanding the phenotypic spectrum of Kenny-Caffey syndrome: a case series and systematic literature review. Journal of Clinical Endocrinology and Metabolism, 108(9), e754-e768. (doi: 10.1210/clinem/dgad147) (PMID:36916904) (PMCID:PMC10438882)

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Context: Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish. Objective: The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate on complications that may arise in these disorders. Design: We clinically and genetically analyzed ten KCS2 patients from seven families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by three researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by two independent researchers. Results: Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low PTH levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23) and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common. Conclusions: Our case series established chronic kidney disease as a new feature of KCS2. In literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.

Item Type:Articles
Additional Information:This work was financially supported by the IMAGEN project which is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships (IMplementation of Advancements in GENetic Kidney Disease, LSHM20009), the Dutch Kidney Foundation (19OP004), the Radboud-Glasgow Collaboration Fund 2020 and the HORIZON EUROPE European Research Council (ERC STG 101040682).
Glasgow Author(s) Enlighten ID:Rios, Dr Francisco and Mackin, Dr Sharon and Perry, Dr Colin and Touyz, Professor Rhian
Authors: Schigt, H., Bald, M., van der Eerden, B. C.J., Gal, L., Ilenwabor, B. P., Konrad, M., Levine, M. A., Li, D., Mache, C. J., Mackin, S., Perry, C., Rios, F. J., Schlingmann, K. P., Storey, B., Trapp, C. M., Verkerk, A. J.M.H., Zillikens, M. C., Touyz, R. M., Hoorn, E. J., Hoenderop, J. G.J., and de Baaij, J. H.F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:Oxford University Press
ISSN (Online):1945-7197
Published Online:14 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Journal of Clinical Endocrinology and Metabolism 108(9):e754-e768
Publisher Policy:Reproduced under a Creative Commons License

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