The FGFR2 gene related Apert and Crouzon Syndrome with Different Craniofacial Dysmorphism: A Systematic Review and Meta-analysis.

Authors

  • Dhiman S Genetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0001-6539-4029
  • Panigrahi I Genetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0001-7375-9892
  • Padhi BK Department of Community Medicine and School of Public Health at the Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0002-2828-2375
  • Gupta S Genetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0001-8682-6521
  • Satapathy P Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
  • Khatib MN Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
  • Gaidhane S One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India
  • Kaur H aGenetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0003-1991-0584
  • Sharma M Department of Otolaryngology Head and Neck Surgery, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012 https://orcid.org/0000-0001-7011-0983
  • Zahiruddin QS Global Health Academy, Division of Evidence Synthesis, School of Epidemiology and Public Health and Research, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher education and Research, Wardha. India
  • Sah R Tribhuvan University Teaching Hospital, Kathmandu 46000, Nepal
  • Kaur K Genetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012
  • Garg M Genetic Metabolic Unit, and Growth and Development unit; Department of Paediatrics, Advanced Paediatrics Center (APC), Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh- 160012

Keywords:

Apert, crouzon, craniofacial, craniosynostosis, dental

Abstract

Background: This study aims to compare Craniofacial dysmorphism like maxillary, mandibular, and dental arch dimensions, and cranial suture fusion prevalence in Apert and Crouzon Syndrome from the publicly available scientific information and also give insights to improve the findings of further studies. The protocol was submitted to the International Prospective Register of Systematic Reviews CRD42023395454 accessed 11 February 2023.

Material and Methods: On a large scale interval from January 2000 to January 2023 a comprehensive search on different database platforms: PubMed, Google Scholar, Cochrane, Web of Science, and Wiley online library. PRISMA (Preferred reporting item for Systematic Review and Meta-Analyses) guidelines were followed to conduct this systematic review. The meta-analysis was carried out by calculating the random effects model and pooled mean proportions with 95% confidence intervals (CI).

Results: A total of 53 studies were considered worthy, but 39 were excluded due to unusable data formats. The I2 index provides a better way of assessing effect size heterogeneity. Forest plots were generated to visualize the heterogeneity of the individual outcome. Subgroup analyses were performed for each outcome to assess the potential, differences in effect sizes. Effect size and heterogeneity of the dental arch are more in CS (I2: 58%, 95%CI 0.01,0.29, P=0.12) and least in AS (I2: 52%;95%CI 0.01;0,27, P=0.15). Effect size and heterogeneity of maxilla of AS patients (I2: 91%, 95%CI 0.09;0.47, P<0.01) and CS (I2: 94%,95%CI 0.07;0.64, P<0.01). We observed significant heterogeneity in AS and CS patients.

Conclusion: This review demonstrates the large variation in cephalometric measurements in CS and AS patients. The CS patient had a smaller skull and mandible volume than the AS patient. AS had an anterior crossbite (p<0.001) and CS had an edge-to-edge bite (p<0.011). CS tends to have short and flat cranial bases, smaller orbital volumes, and cleft palates.

References

Al-Namnam, N., Hariri, F., Thong, M., & Rahman, Z. (2019). Crouzon syndrome: Genetic and intervention review. Journal of Oral Biology and Craniofacial Research, 9(1), 37-39.

Alsaeed, S., Huynh, N., Wensley, D., Lee, K., Hamoda, M. M., Ayers, E., Sutherland, K., & Almeida, F. R. (2023). Orthodontic and Facial Characteristics of Craniofacial Syndromic Children with Obstructive Sleep Apnea. Diagnostics, 13(13), 2213.

Andersson, L., Kahnberg, K.-E., & Pogrel, M. A. (2010). Oral and maxillofacial surgery. John Wiley & Sons.

Azoury, S. C., Reddy, S., Shukla, V., & Deng, C.-X. (2017). Fibroblast growth factor receptor 2 (FGFR2) mutation related syndromic craniosynostosis. International journal of biological sciences, 13(12), 1479.

Balshem, H., Helfand, M., Schünemann, H. J., Oxman, A. D., Kunz, R., Brozek, J., Vist, G. E., Falck-Ytter, Y., Meerpohl, J., & Norris, S. (2011). GRADE guidelines: 3. Rating the quality of evidence. Journal of clinical epidemiology, 64(4), 401-406.

Balyen, L., Balyen, L. D., & Pasa, S. (2017). Clinical characteristics of Crouzon syndrome. Oman journal of ophthalmology, 10(2), 120-122.

Bhoj, E. J., & Zackai, E. H. (2021). Craniosynostosis syndromes. Cassidy and Allanson's Management of Genetic Syndromes, 241-251.

Choudhary, A., Edgar, M., Raman, S., Alkureishi, L. W., & Purnell, C. A. (2023). Craniometric and Aesthetic Outcomes in Craniosynostosis Surgery: A Systematic Review and Meta-Analysis. The Cleft Palate Craniofacial Journal, 10556656231204506.

Das, S., & Munshi, A. (2018). Research advances in Apert syndrome. Journal of Oral Biology and Craniofacial Research, 8(3), 194-199.

Di Rocco, F., Rossi, M., Verlut, I., Szathmari, A., Beuriat, P. A., Chatron, N., Chauvel-Picard, J., Mottolese, C., Monin, P., & Vinchon, M. (2023). Clinical interest of molecular study in cases of isolated midline craniosynostosis. European Journal of Human Genetics, 1-8.

Elarjani, T., Almutairi, O. T., Alhussinan, M., Alturkistani, A., Alotaibi, F. S., Bafaquh, M., & Alotaibi, F. E. (2021). Bibliometric analysis of the top 100 most cited articles on craniosynostosis. Child's Nervous System, 37, 587-597.

Elmi, P., Reitsma, J. H., Buschang, P., Wolvius, E., & Ongkosuwito, E. (2015). Mandibular asymmetry in patients with the Crouzon or Apert syndrome. The Cleft Palate-Craniofacial Journal, 52(3), 327-335.

Faasse, M., & Mathijssen, I. M. (2023). Guideline on Treatment and Management of Craniosynostosis: Patient and Family Version. Journal of Craniofacial Surgery, 34(1), 418-433.

Fernandes, M. B., Maximino, L. P., Perosa, G. B., Abramides, D. V., Passos‐Bueno, M. R., & Yacubian‐Fernandes, A. (2016). Apert and Crouzon syndromes—cognitive development, brain abnormalities, and molecular aspects. American Journal of Medical Genetics Part A, 170(6), 1532-1537.

Forte, A. J., Alonso, N., Persing, J. A., Pfaff, M. J., Brooks, E. D., & Steinbacher, D. M. (2014). Analysis of midface retrusion in Crouzon and Apert syndromes. Plastic and Reconstructive Surgery, 134(2), 285-293.

Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta‐analysis. Statistics in medicine, 21(11), 1539-1558.

Hoshino, Y., Takechi, M., Moazen, M., Steacy, M., Koyabu, D., Furutera, T., Ninomiya, Y., Nuri, T., Pauws, E., & Iseki, S. (2023). Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis. Journal of Anatomy, 242(3), 387-401.

Junaid, M., Slack-Smith, L., Wong, K., Baynam, G., Calache, H., Hewitt, T., & Leonard, H. (2023). Epidemiology of hospital admissions for craniosynostosis in Australia: a population-based study. The Cleft Palate Craniofacial Journal, 60(5), 569-576.

Khonsari, R. H., Way, B., Nysjö, J., Odri, G. A., Olszewski, R., Evans, R. D., Dunaway, D. J., Nyström, I., & Britto, J. A. (2016). Fronto-facial advancement and bipartition in Crouzon–Pfeiffer and Apert syndromes: Impact of fronto-facial surgery upon orbital and airway parameters in FGFR2 syndromes. Journal of Cranio-Maxillofacial Surgery, 44(10), 1567-1575.

Kiziltug, E., Duy, P. Q., Allington, G., Timberlake, A. T., Kawaguchi, R., Long, A. S., Almeida, M. N., DiLuna, M. L., Alper, S. L., & Alperovich, M. (2023). Concurrent impact of de novo mutations on cranial and cortical development in nonsyndromic craniosynostosis. Journal of Neurosurgery: Pediatrics, 1(aop), 1-14.

Ko, J. M. (2016). Genetic syndromes associated with craniosynostosis. Journal of Korean Neurosurgical Society, 59(3), 187.

Kobayashi, Y., Ogura, K., Hikita, R., Tsuji, M., & Moriyama, K. (2021). Craniofacial, oral, and cervical morphological characteristics in Japanese patients with Apert syndrome or Crouzon syndrome. European Journal of Orthodontics, 43(1), 36-44.

Koca, T. T. (2016). Apert syndrome: a case report and review of the literature. Northern clinics of Istanbul, 3(2), 135.

Kreiborg, S., & Cohen Jr, M. M. (2010). Ocular manifestations of Apert and Crouzon syndromes: qualitative and quantitative findings. Journal of Craniofacial Surgery, 21(5), 1354-1357.

Kumari, K., Saleh, I., Taslim, S., Ahmad, S., Hussain, I., Munir, Z., Javed, T., Virk, M. F. I., Javed, S., & Bisharat, P. (2023). Unraveling the Complexity of Apert Syndrome: Genetics, Clinical Insights, and Future Frontiers. Cureus, 15(10).

Kyprianou, C., & Chatzigianni, A. (2018). Crouzon syndrome: a comprehensive review. Balkan Journal of Dental Medicine, 22(1), 1-6.

Lu, X., Forte, A. J., Wilson, A., Steinbacher, D. M., Alperovich, M., Alonso, N., & Persing, J. A. (2020). Cranial fossa volume and morphology development in Apert syndrome. Plastic and Reconstructive Surgery, 145(4), 790e-802e.

Lu, X., Forte, A. J., Wilson, A. T., Park, K. E., Allam, O., Alperovich, M., Steinbacher, D. M., Alonso, N., & Persing, J. A. (2021). Respective roles of craniosynostosis and syndromic influences on cranial fossa development. Plastic and Reconstructive Surgery, 148(1), 145-156.

Lu, X., Sawh-Martinez, R., Forte, A. J., Wu, R., Cabrejo, R., Wilson, A., Steinbacher, D. M., Alperovich, M., Alonso, N., & Persing, J. A. (2019). Classification of subtypes of Apert syndrome, based on the type of vault suture synostosis. Plastic and Reconstructive Surgery–Global Open, 7(3), e2158.

Luong, A. L. T., Ho, T. T., Hoang, H., Nguyen, T. Q., Ho, T. C., Tran, P. D., Hoang, T. T., Nguyen, N. T., & Chu, H. H. (2019). Detection of G338R FGFR2 mutation in a Vietnamese patient with Crouzon syndrome. Biomedical reports, 10(2), 107-112.

Ma, L., Chang, Q., Pei, F., Liu, M., Zhang, W., Hong, Y.-K., Chai, Y., & Chen, J.-F. (2023). Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis. Cell Stem Cell.

Massimi, L., Bianchi, F., Frassanito, P., Calandrelli, R., Tamburrini, G., & Caldarelli, M. (2019). Imaging in craniosynostosis: when and what? Child's Nervous System, 35, 2055-2069.

Morice, A., Cornette, R., Giudice, A., Collet, C., Paternoster, G., Arnaud, É., Galliani, E., Picard, A., Legeai-Mallet, L., & Khonsari, R. (2020). Early mandibular morphological differences in patients with FGFR2 and FGFR3-related syndromic craniosynostoses: A 3D comparative study. Bone, 141, 115600.

Motch Perrine, S. M., Stecko, T., Neuberger, T., Jabs, E. W., Ryan, T. M., & Richtsmeier, J. T. (2017). Integration of brain and skull in prenatal mouse models of Apert and Crouzon syndromes. Frontiers in Human Neuroscience, 11, 369.

Munarriz, P. M., Pascual, B., Castaño-Leon, A. M., García-Recuero, I., Redondo, M., de Aragón, A. M., & Romance, A. (2020). Apert syndrome: Cranial procedures and brain malformations in a series of patients. Surgical Neurology International, 11.

Munib, N., Khan, Q. A., Rodriguez, A. R., Belay, N. F., Shah, R., & Afzal, M. (2023). Clinical Manifestations of Cruzon Syndrome.

Nur, B. G., Pehlivanoğlu, S., Mıhçı, E., Çalışkan, M., Demir, D., Alper, Ö. M., Kayserili, H., & Lüleci, G. (2014). Clinicogenetic study of Turkish patients with syndromic craniosynostosis and literature review. Pediatric neurology, 50(5), 482-490.

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., & Brennan, S. E. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj, 372.

Pinto, R. d. O., Tonello, C., Peixoto, A. P., de Jesus, A. S., Santos-Pinto, A. d., & Raveli, D. B. (2023). Three-Dimensional Evaluation of Dental Arches in Individuals with Syndromic Craniosynostosis. International Journal of Dentistry, 2023.

Pollock, A., Farmer, S. E., Brady, M. C., Langhorne, P., Mead, G. E., Mehrholz, J., van Wijck, F., & Wiffen, P. J. (2016). An algorithm was developed to assign GRADE levels of evidence to comparisons within systematic reviews. Journal of clinical epidemiology, 70, 106-110.

Raposo-Amaral, C. E., Neto, J. G. J., Denadai, R., Raposo-Amaral, C. M., & Raposo-Amaral, C. A. (2014). Patient-reported quality of life in highest-functioning Apert and Crouzon syndromes: a comparative study. Plastic and Reconstructive Surgery, 133(2), 182e-191e.

Reitsma, J. H., Balk-Leurs, I. H., Ongkosuwito, E. M., Wattel, E., & Prahl-Andersen, B. (2014). Dental maturation in children with the syndrome of crouzon and apert. The Cleft Palate-Craniofacial Journal, 51(6), 639-644.

Reitsma, J. H., Ongkosuwito, E. M., Buschang, P. H., Adrichem, L. N. V., & Prahl-Andersen, B. (2013). Craniofacial stability in patients with Crouzon or Apert syndrome after Le Fort III distraction osteogenesis. The Cleft Palate-Craniofacial Journal, 50(5), 561-569.

Rostamzad, P., Arslan, Z. F., Mathijssen, I. M., Koudstaal, M. J., Pleumeekers, M. M., Versnel, S. L., & Loudon, S. E. (2022). Prevalence of ocular anomalies in craniosynostosis: a systematic review and meta-analysis. Journal of Clinical Medicine, 11(4), 1060.

Sakamoto, Y., Takenouchi, T., Miwa, T., & Kishi, K. (2021). Assessment of long-term quality of life in patients with syndromic craniosynostosis. Journal of Plastic, Reconstructive & Aesthetic Surgery, 74(2), 336-340.

Sawh-Martinez, R., & Steinbacher, D. M. (2019). Syndromic craniosynostosis. Clinics in Plastic Surgery, 46(2), 141-155.

Shlobin, N. A., Baticulon, R. E., Ortega, C. A., Du, L., Bonfield, C. M., Wray, A., Forrest, C. R., & Dewan, M. C. (2022). Global epidemiology of craniosynostosis: a systematic review and meta-analysis. World neurosurgery, 164, 413-423. e413.

Spruijt, B., Rijken, B. F., den Ottelander, B. K., Joosten, K. F., Lequin, M. H., Loudon, S. E., van Veelen, M.-L. C., & Mathijssen, I. M. (2016). First vault expansion in Apert and Crouzon-Pfeiffer syndromes: front or back? Plastic and Reconstructive Surgery, 137(1), 112e-121e.

Stanton, E., Urata, M., Chen, J.-F., & Chai, Y. (2022). The clinical manifestations, molecular mechanisms and treatment of craniosynostosis. Disease Models & Mechanisms, 15(4), dmm049390.

Tan, A. P., & Mankad, K. (2018). Apert syndrome: magnetic resonance imaging (MRI) of associated intracranial anomalies. Child's Nervous System, 34, 205-216.

Taylor, J. A., & Bartlett, S. P. (2017). What’s new in syndromic craniosynostosis surgery? Plastic and Reconstructive Surgery, 140(1), 82e-93e.

Timberlake, A. T., Kiziltug, E., Jin, S. C., Nelson-Williams, C., Loring, E., Analysis, Y. C. f. G., Allocco, A., Marlier, A., Banka, S., & Stuart, H. (2023). De novo mutations in the BMP signaling pathway in lambdoid craniosynostosis. Human Genetics, 142(1), 21-32.

Tønne, E., Due-Tønnessen, B. J., Wiig, U., Stadheim, B. F., Meling, T. R., Helseth, E., & Heimdal, K. R. (2020). Epidemiology of craniosynostosis in Norway. Journal of Neurosurgery: Pediatrics, 26(1), 68-75.

Viechtbauer, W., & Cheung, M. W. L. (2010). Outlier and influence diagnostics for meta‐analysis. Research synthesis methods, 1(2), 112-125.

Wang, N. (2018). How to conduct a meta-analysis of proportions in R: a comprehensive tutorial. New York: John Jay College for Criminal Justice.

Downloads

Published

2024-12-31

How to Cite

Dhiman, S., Panigrahi, I., Padhi , B. K., Gupta, S., Satapathy, P., Khatib, M. N., … Garg, M. (2024). The FGFR2 gene related Apert and Crouzon Syndrome with Different Craniofacial Dysmorphism: A Systematic Review and Meta-analysis. Biomedical Review: Journal of Basic and Applied Medical Sciences, 11(1), 25–33. Retrieved from https://biomedicalreview.in/index.php/jbams/article/view/74

Issue

Vol. 11 No. 1 (2024): Jan-Dec

Section

Review Article

License

Copyright (c) 2024 Dhiman S, Panigrahi I, Padhi BK, Gupta S, Satapathy P, Khatib MN, Gaidhane S, Kaur H, Sharma M, Zahiruddin QS, Sah R, Kaur K, Garg M

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Biomedical Review follows the Creative Commons CC-BY license (Attribution). It means Authors can use, reuse and build upon the material published in the journal but only for non-commercial purposes. Every article published in the Journal clearly mentioned licensing terms between author/authors and publisher (Siddharth Health Research and Social Welfare Society) as the logo of Creative Commons CC-BY license (Attribution) https://creativecommons.org/licenses/by/4.0/.