Acromicric dysplasia due to a novel missense mutation in the fibrillin 1 gene in a three-generation family

Friederike Quitter; Monika Flury; Stephan Waldmueller; Tina Schubert; Katrin Koehler; Angela Huebner

doi:10.1515/jpem-2022-0287

Article

Acromicric dysplasia due to a novel missense mutation in the fibrillin 1 gene in a three-generation family

Friederike Quitter , Monika Flury , Stephan Waldmueller , Tina Schubert , Katrin Koehler and Angela Huebner

Published/Copyright: August 9, 2022

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 11

Abstract

Objectives

Short stature is one of the most common reasons for consulting a paediatric endocrinologist. Targeted diagnosis of familial short stature can be challenging due to a broad spectrum of differential diagnoses.

Case presentation

Here we report a novel mutation in the fibrillin 1 gene (FBN1) in six family members causing a mild phenotype of acromicric dysplasia. Additionally, we present the effects of growth hormone therapy in one of the affected children.

Conclusions

Acromicric dysplasia is a very rare skeletal dysplasia with a prevalence of <1 of 1.000.000 with only about 60 cases being reported worldwide. It is characterized by short stature, acromelia, mild facial dysmorphy but normal intelligence. This study aims to exemplify the clinical and molecular features of FBN1-related acromicric dysplasia and illustrates its pleiotropy by presenting a new, mild phenotype.

Keywords: acromicric dysplasia; FBN1 ; short stature

Corresponding author: Friederike Quitter, MD, Children’s Hospital, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany, Phone: +49-351-458 2345, Fax: +49-351-458 6333, E-mail: Friederike.Quitter@ukdd.de

Funding source: Else Kröner-Fresenius-Stiftung

Funding source: Eva Luise und Horst Köhler Stiftung

Acknowledgments

We thank the family members who participated in this case study. We particularly thank Dana Landgraf for technical assistance and Wayne Lang for proofreading the manuscript.

Research funding: This work was supported by the Else Kröner-Fresenius–Stiftung and the Eva Luise und Horst Köhler–Stiftung within the Clinician Scientist program RISE.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Not applicable.

References

1. Bonafe, L, Cormier-Daire, V, Hall, C, Lachman, R, Mortier, G, Mundlos, S, et al.. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet 2015;167A:2869–92. https://doi.org/10.1002/ajmg.a.37365.Search in Google Scholar PubMed

2. Le Goff, C, Mahaut, C, Wang, LW, Allali, S, Abhyankar, A, Jensen, S, et al.. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet 2011;89:7–14. https://doi.org/10.1016/j.ajhg.2011.05.012.Search in Google Scholar PubMed PubMed Central

3. Faivre, L, Le Merrer, M, Baumann, C, Polak, M, Chatelain, P, Sulmont, V, et al.. Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance. J Med Genet 2001;38:745–9. https://doi.org/10.1136/jmg.38.11.745.Search in Google Scholar PubMed PubMed Central

4. Allali, S, Le Goff, C, Pressac-Diebold, I, Pfennig, G, Mahaut, C, Dagoneau, N, et al.. Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia. J Med Genet 2011;48:417–21. https://doi.org/10.1136/jmg.2010.087544.Search in Google Scholar PubMed PubMed Central

5. Sakai, LY, Keene, DR, Renard, M, De Backer, J. FBN1: the disease-causing gene for Marfan syndrome and other genetic disorders. Gene 2016;591:279–91. https://doi.org/10.1016/j.gene.2016.07.033.Search in Google Scholar PubMed PubMed Central

6. Pereira, L, D’Alessio, M, Ramirez, F, Lynch, JR, Sykes, B, Pangilinan, T, et al.. Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet 1993;2:961–8. https://doi.org/10.1093/hmg/2.7.961.Search in Google Scholar PubMed

7. Yu, J, Urban, J. Immunolocalisation of fibrillin microfibrils in the calf metacarpal and vertebral growth plate. J Anat 2013;223:641–50. https://doi.org/10.1111/joa.12123.Search in Google Scholar PubMed PubMed Central

8. Le Goff, C, Cormier-Daire, V. Chondrodysplasias and TGFβ signaling. Bonekey Rep 2015;4:642. https://doi.org/10.1038/bonekey.2015.9.Search in Google Scholar PubMed PubMed Central

9. Yorifuji, T, Higuchi, S, Kawakita, R. Growth hormone treatment for achondroplasia. Pediatr Endocrinol Rev 2018;16:123–8. https://doi.org/10.17458/per.vol16.2018.yhk.ghachondroplasia.Search in Google Scholar PubMed

10. Jin, HS, Song, HY, Cho, SY, Ki, CS, Yang, SH, Kim, OH, et al.. Acromicric dysplasia caused by a novel heterozygous mutation of FBN1 and effects of growth hormone treatment. Ann Lab Med 2017;37:92–4. https://doi.org/10.3343/alm.2017.37.1.92.Search in Google Scholar PubMed PubMed Central

Received: 2022-06-03

Accepted: 2022-07-10

Published Online: 2022-08-09

Published in Print: 2022-11-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2022-0287

Keywords for this article

acromicric dysplasia; FBN1; short stature