Clinical and molecular genetic features of cases of Floating-Harbor syndrome

Floating-Harbor syndrome is an autosomal dominant genetic disorder that is part of a group of growth retardation. The main clinical features of syndrome are short stature, delayed speech development and peculiar facial features: triangular face with a narrow chin, deeply set eyes, a short filter, a macrostomy, a nose with a narrow bridge and wide base and tip, a drooping columella. The syndrome is associated with heterozygous pathogenic variants were truncating and occurred in 33 and 34 exons of SRCAP. Heterogeneity and the absence of specific clinical features complicates the formulation of this diagnosis, which necessitates molecular genetic verification. In this paper, we present the first description of 6 patients with proven Floating-Harbor syndrome in the Russian Federation.

1. Lacombe D, Patton MA, Elleau C, Battin J. Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance. Eur J Pediatr. 1995;154(8):658-61. doi: https://doi.org/10.1007/BF02079072

2. Pelletier G, Feingold M. Case report 1. Syndrome Identification J. 1973;1:8–9

3. Nikkel SM, Dauber A, de Munnik S, Connolly M, Hood RL, Caluseriu O, et al. The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP. Orphanet J Rare Dis. 2013;8:63. doi: https://doi.org/10.1186/1750-1172-8-63

4. Seifert W, Meinecke P, Krüger G, Rossier E, Heinritz W, Wüsthof A, Horn D. Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome. BMC Med Genet. 2014;15:127. doi: https://doi.org/10.1186/s12881-014-0127-0

5. Kehrer M, Beckmann A, Wyduba J, Finckh U, Dufke A, Gaiser U, Tzschach A. Floating-Harbor syndrome: SRCAP mutations are not restricted to exon 34. Clin Genet. 2014;85(5):498-9. doi: https://doi.org/10.1111/cge.12199

6. Hood RL, Lines MA, Nikkel SM, Schwartzentruber J, Beaulieu C, Nowaczyk MJ, et al. Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. Am J Hum Genet. 2012;90(2):308-13. doi: https://doi.org/10.1016/j.ajhg.2011.12.001

7. Messina G, Prozzillo Y, Delle Monache F, Santopietro MV, Atterrato MT, Dimitri P. The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome. BMC Biol. 2021;19(1):184. doi: https://doi.org/10.1186/s12915-021-01109-x

8. 8. Leisti J, Hollister DW, Rimoin DL. The Floating-Harbor syndrome. Birth Defects Orig Artic Ser. 1975;11(5):305

9. Galli-Tsinopoulou A, Kyrgios I, Emmanouilidou E, Maggana I, Kotanidou E, Kokka P, Stylianou C. Growth hormone deficiency: an unusual presentation of floating harbor syndrome. Hormones (Athens). 2011;10(3):236-40. doi: https://doi.org/10.14310/horm.2002.1314

10. Homma TK, Freire BL, Honjo R, Dauber A, Funari MFA, et al. Growth and Clinical Characteristics of Children with Floating-Harbor Syndrome: Analysis of Current Original Data and a Review of the Literature. Horm Res Paediatr. 2019;92(2):115-123. doi: https://doi.org/10.1159/000503782

11. Bo H, Jiang L, Zheng J, Sun J. Floating-Harbor Syndrome treated with recombinant human growth hormone: a case report and literature review. Front Pediatr. 2021;9:747353. doi: https://doi.org/10.3389/fped.2021.747353

12. Vardarajan BN, Tosto G, Lefort R, Yu L, Bennett DA, et al. Ultra-rare mutations in SRCAP segregate in Caribbean Hispanic families with Alzheimer disease. Neurol. Genet. 2017;3(5):e178. doi: https://doi.org/10.1212/NXG.0000000000000178

13. Iossifov I, O’Roak BJ, Sanders SJ, Ronemus M, Krumm N, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014;515(7526):216-21. doi: https://doi.org/10.1038/nature13908

14. Rots D, Chater-Diehl E, Dingemans AJ, Goodman SJ, Siu MT, et al. Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature. AJHG. 2021;108(6):1053-68. doi: https://doi.org/10.1016/j.ajhg.2021.04.008

15. Johnston H, Kneer J, Chackalaparampil I, Yaciuk P, Chrivia J. Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. J Biol Chem. 1999;274(23):16370-6. doi: https://doi.org/10.1074/jbc.274.23.16370

16. Zhao J, Favero DS, Qiu J, Roalson EH, Neff MM. Insights into the evolution and diversification of the AT-hook Motif Nuclear Localized gene family in land plants. BMC Plant Biol. 2014;14:266. doi: https://doi.org/10.1186/s12870-014-0266-7

17. Yu J, Sui F, Gu F, Li W, Yu Z, Wang Q, He S, Wang L, Xu Y. Structural insights into histone exchange by human SRCAP complex. Cell Discov. 2024;10(1):15. doi: https://doi.org/10.1038/s41421-023-00640-1

18. Park E, Kim Y, Ryu H, Kowall NW, Lee J, Ryu H. Epigenetic mechanisms of Rubinstein-Taybi syndrome. Neuromolecular Med. 2014;16(1):16-24. doi: https://doi.org/10.1007/s12017-013-8285-3

19. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi: https://doi.org/10.1038/gim.2015.30

20. Ryzhkova OP, Kardymon OL, Prohorchuk EB, et al. Guidelines for the interpretation of human DNA sequence data from massively parallel sequencing (MPS) methods (2018 revision, version 2).Medical Genetics. 2019;18(2):3-23. (In Russ.) doi: https://doi.org/10.25557/2073-7998.2019.02.3-23