Abstract
Introduction
Fraser syndrome, named after George Fraser, is an autosomal recessive disorder showing a highly variable interfamilial phenotypic variation, with malformations ranging from minor symptoms to lethal anomalies like renal agenesis, incompatible with survival. Limb reduction defects have not been reported to be associated with it.
Case presentation
A 21-year-old primigravida presented to the antenatal outpatient department with a level two targeted anomaly scan report suggestive of severe oligohydramnios with suspected renal agenesis. The cranial vault bones were compressed, and orbital globes and lenses could not be visualized. Renal agenesis was confirmed due to sleeping adrenals sign, non-visualization of the urinary bladder, and Doppler of renal arteries. A detailed examination of the fetal head in the sagittal section showed the absence of an eye globe and lens, arousing suspicion of Fraser syndrome. After pregnancy termination, a complete fetal autopsy was done to look for any additional findings.
Conclusion
Patients who have a syndromic mix of acrofacial and urogenital abnormalities with or without cryptophthalmos should be evaluated for Fraser syndrome, which can be diagnosed by clinical examination and perinatal autopsy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Not applicable.
References
Kabra M, Gulati S, Ghosh M, Menon PS (2000) Fraser-cryptophthalmos syndrome. Indian J Pediatr 67(10):775–778. https://doi.org/10.1007/BF02723939
Narang M, Kumar M, Shah D (2008) Fraser-cryptophthalmos syndrome with colonic atresia. Indian J Pediatr 75(2):189–191. https://doi.org/10.1007/s12098-008-0030-9
Berg C, Geipel A, Germer U, Pertersen-Hansen A, Koch-Dörfler M, Gembruch U (2001) Prenatal detection of Fraser syndrome without cryptophthalmos: case report and review of the literature. Ultrasound Obstet Gynecol 18(1):76–80. https://doi.org/10.1046/j.1469-0705.2001.00374.x
Slavotinek AM, Tifft CJ (2002) Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet 39(9):623–633. https://doi.org/10.1136/jmg.39.9.623
Thomas IT, Frias JL, Felix V, Sanchez de Leon L, Hernandez RA, Jones MC (1986) Isolated and syndromic cryptophthalmos. Am J Med Genet 25(1):85–98. https://doi.org/10.1002/ajmg.1320250111
van Haelst, M. M., Scambler, P. J., Fraser Syndrome Collaboration Group, & Hennekam, R. C (2007) Fraser syndrome: a clinical study of 59 cases and evaluation of diagnostic criteria. Am J Med Genet A 143A(24):3194–3203. https://doi.org/10.1002/ajmg.a.31951
Ramsing M, Rehder H, Holzgreve W, Meinecke P, Lenz W (1990) Fraser syndrome (cryptophthalmos with syndactyly) in the fetus and newborn. Clin Genet 37(2):84–96. https://doi.org/10.1111/j.1399-0004.1990.tb03484.x
Tessier A, Sarreau M, Pelluard F, André G, Blesson S, Bucourt M, Dechelotte P, Faivre L, Frébourg T, Goldenberg A, Goua V, Jeanne-Pasquier C, Guimiot F, Laquerriere A, Laurent N, Lefebvre M, Loget P, Maréchaud M, Mechler C, Perez MJ, … Guerrot AM (2016) Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases. Prenatal Diagn 36(13):1270–1275. https://doi.org/10.1002/pd.4971
Comstock JM, Putnam AR, Opitz JM, Pysher TJ, Szakacs J (2005) Prenatal death in Fraser syndrome. Fetal Pediatr Pathol 24(4–5):223–238. https://doi.org/10.1080/15227950500405353
Serville F, Carles D, Broussin B (1989) Fraser syndrome: prenatal ultrasonic detection. Am J Med Genet 32(4):561–563. https://doi.org/10.1002/ajmg.1320320435
Kalpana Kumari MK, Kamath S, Mysorekar VV, Nandini G (2008) Fraser syndrome. Indian J Pathol Microbiol 51(2):228–229. https://doi.org/10.4103/0377-4929.41664
Gattuso J, Patton MA, Baraitser M (1987) The clinical spectrum of the Fraser syndrome: report of three new cases and review. J Med Genet 24(9):549–555. https://doi.org/10.1136/jmg.24.9.549
Allali B, Hamdani M, Lamari H, Rais L, Benhaddou M, Kettani A, Lahbil D, Amraoui A, Zaghloul K (2006) Syndrome de Fraser [Fraser syndrome. A case report]. J Franc D’ophtalmol 29(2):184–187. https://doi.org/10.1016/s0181-5512(06)73769-x
Boyd PA, Keeling JW, Lindenbaum RH (1988) Fraser syndrome (cryptophthalmos-syndactyly syndrome): a review of eleven cases with postmortem findings. Am J Med Genet 31(1):159–168. https://doi.org/10.1002/ajmg.1320310119
McGregor L, Makela V, Darling SM, Vrontou S, Chalepakis G, Roberts C, Smart N, Rutland P, Prescott N, Hopkins J, Bentley E, Shaw A, Roberts E, Mueller R, Jadeja S, Philip N, Nelson J, Francannet C, Perez-Aytes A, Megarbane A, … Scambler PJ (2003) Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet 34(2):203–208. https://doi.org/10.1038/ng1142
Pavlakis E, Chiotaki R, Chalepakis G (2011) The role of Fras1/Frem proteins in the structure and function of basement membrane. Int J Biochem Cell Biol 43(4):487–495. https://doi.org/10.1016/j.biocel.2010.12.016
Mbonda A, Endomba FT, Kanmounye US, Nkeck JR, Tochie JN (2019) Diagnosis of Fraser syndrome missed out until the age of six months old in a low-resource setting: a case report. BMC Pediatr 19(1):292. https://doi.org/10.1186/s12887-019-1673-6
Vogel MJ, van Zon P, Brueton L, Gijzen M, van Tuil MC, Cox P, Schanze D, Kariminejad A, Ghaderi-Sohi S, Blair E, Zenker M, Scambler PJ, Ploos van Amstel HK, van Haelst MM (2012) Mutations in GRIP1 cause Fraser syndrome. J Med Genet 49(5):303–306. https://doi.org/10.1136/jmedgenet-2011-100590
Dumitru A, Costache M, Lazaroiu AM, Simion G, Secara D, Cirstoiu M, Emanoil A, Georgescu TA, Sajin M (2016) Fraser syndrome – a case report and review of literature. Maedica 11(1):80–83
Vijayaraghavan SB, Suma N, Lata S, Kamakshi K (2005) Prenatal sonographic appearance of cryptophthalmos in Fraser syndrome. Ultrasound Obstet Gynecol 25(6):629–630. https://doi.org/10.1002/uog.1905
Funding
The authors have no financial or personal relationship with any third party whose interests could be positively or negatively influenced by the article’s content. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Contributions
MM—project development, data collection and management, data analysis and manuscript writing. AK—project development, data collection and management, data analysis and manuscript writing. AS—data collection and management, and manuscript writing. MC—data analysis and manuscript editing. RM—data analysis and manuscript editing. NK—data analysis and manuscript editing. SR—data analysis and manuscript editing. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interests.
Ethical approval and consent to participate
Not applicable.
Consent to publish
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Mangla, M., Kaliappan, A., Srirambhatla, A. et al. Fraser syndrome with limb reduction defect: a rare and unique anatomic variation. Surg Radiol Anat 46, 501–506 (2024). https://doi.org/10.1007/s00276-024-03299-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00276-024-03299-9