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Mundhofir FE, Sistermans EA, Faradz SM, Hamel BC
Correspondence: Prof Sultana MH Faradz, sultana@indosat.net.id
ABSTRACT
Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular analysis detected p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has been frequently described, this is the first clinical report of AS confirmed by molecular analysis in Indonesia. The difference in severity of clinical features in the two patients may be consistent with a genotype-phenotype correlation of the FGFR2mutation. The management of individuals with AS is best achieved within a multidisciplinary setting. However, in most developing countries, early intervention may be delayed due to late diagnosis, a lack of facilities and financial constraints. This report underpins the benefits of early diagnosis for AS management.
Keywords: Apert syndrome, FGFR2, Indonesia
Singapore Med J 2013; 54(3): e72–e75; doi:10.11622/smedj.2013055
REFERENCES
| 1. Gorlin RJ, Cohen MM Jr, Hennekam RCM. Syndromes of the Head and Neck. 4th ed. Oxford: Oxford University Press, 2002. PMCid:1735218 | ||||
| 2. Cohen MM, Kreiborg S. The Central Nervous System in the ApertSyndrome. Am J Med Genet 1990; 35:36-45. http://dx.doi.org/10.1002/ajmg.1320350108 | ||||
| 3. Tolarova MM, Harris JA, Ordway DE, Vargervik K. Birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity in Apert syndrome. Am J Med Genet 1997; 72:394-8. http://dx.doi.org/10.1002/(SICI)1096-8628(19971112)72:4<394::AID-AJMG4>3.0.CO;2-R | ||||
| 4. Wilkie AO, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 1995; 9:165-72. http://dx.doi.org/10.1038/ng0295-165 | ||||
| 5. Glaser RL, Broman KW, Schulman RL, et al. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet 2003; 73:939-47. http://dx.doi.org/10.1086/378419 | ||||
| 6. Bochukova EG, Roscioli T, Hedges DJ, et al. Rare mutations of FGFR2 causing apert syndrome: identification of the first partial gene deletion, and an Alu element insertion from a new subfamily. Hum Mutat 2009; 30:204-11. http://dx.doi.org/10.1002/humu.20825 | ||||
| 7. Oldridge M, Zackai EH, Donald-McGinn DM, et al. De novo alu-element insertions in FGFR2 identify a distinct pathological basis for Apert syndrome. Am J Hum Genet 1999; 64:446-61. http://dx.doi.org/10.1086/302245 | ||||
| 8. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16:1215. http://dx.doi.org/10.1093/nar/16.3.1215 | ||||
| 9. Lajeunie E, Cameron R, El Ghouzzi V, et al. Clinical variability in patients with Apert's syndrome. J Neurosurg 1999; 90:443-7. http://dx.doi.org/10.3171/jns.1999.90.3.0443 | ||||
| 10. Slaney SF, Oldridge M, Hurst JA, et al. Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome. Am J Hum Genet 1996; 58:923-32. PMid:8651276 PMCid:1914616 | ||||
| 11. von Gernet S, Golla A, Ehrenfels Y, Schuffenhauer S, Fairley JD. Genotypephenotype analysis in Apert syndrome suggests opposite effects of the two recurrent mutations on syndactyly and outcome of craniofacial surgery. Clin Genet 2000; 57:137-9. http://dx.doi.org/10.1034/j.1399-0004.2000.570208.x | ||||
| 12. Moloney DM, Slaney SF, Oldridge M, et al. Exclusive paternal origin of new mutations in Apert syndrome. Nat Genet 1996; 13:48-53. http://dx.doi.org/10.1038/ng0596-48 | ||||
| 13. Athanasiadis AP, Zafrakas M, Polychronou P, et al. Apert syndrome: the current role of prenatal ultrasound and genetic analysis in diagnosis and counselling. Fetal Diagn Ther 2008; 24:495-98. http://dx.doi.org/10.1159/000181186 | ||||
| 14. David AL, Turnbull C, Scott R, et al. Diagnosis of Apert syndrome in the second-trimester using 2D and 3D ultrasound. Prenat Diagn 2007; 27:629-32. http://dx.doi.org/10.1002/pd.1758 | ||||
| 15. Marucci DD, Dunaway DJ, Jones BM, Hayward RD. Raised intracranial pressure in Apert syndrome. Plast Reconstr Surg 2008; 122:1162-8. http://dx.doi.org/10.1097/PRS.0b013e31818458f0 | ||||