Chromosome 6p25 deletion syndrome: A case report and review of ophthalmic features.
6p25 deletion
Axenfeld-Rieger syndrome
FOXC1
anterior segment dysgenesis
corectopia
posterior embryotoxon
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
30
12
2022
received:
19
09
2022
accepted:
07
03
2023
medline:
11
5
2023
pubmed:
22
3
2023
entrez:
21
3
2023
Statut:
ppublish
Résumé
The 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated with the syndrome, although this relationship has not been well characterized to date. We conducted a systematic literature review to highlight the ocular features in patients with this deletion syndrome and describe a 7-month-old female who has a 6.07 MB 6p25.1p25.3 deletion and a 4.25 MB 17q25.3 duplication. Our patient presented with multiple congenital anomalies, including macrocephaly, frontal bossing, low set ears, tent-shaped mouth, saddle nose, flat midface, and hearing impairment. Her ophthalmic features included proptosis, down-slanting palpebral fissures, hypertelorism, nystagmus, bilateral posterior embryotoxon, and decentered and abnormally shaped pupils. A systematic review of the published cases with sufficient clinical eye descriptions included 63 cases with a confirmed 6p25 deletion. The most common eye findings observed were posterior embryotoxon, iris hypoplasia, corectopia, cornea opacity, and glaucoma.
Identifiants
pubmed: 36941760
doi: 10.1002/ajmg.a.63186
doi:
Types de publication
Systematic Review
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1639-1645Informations de copyright
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
Références
Aldinger, K. A., Lehmann, O. J., Hudgins, L., Chizhikov, V. V., Bassuk, A. G., Ades, L. C., Krantz, I. D., Dobyns, W. B., & Millen, K. J. (2009). FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nature Genetics, 41(9), 1037-1042. https://doi.org/10.1038/ng.422
Anderlid, B.-M., Schoumans, J., Hallqvist, Å., Ståhl, Y., Wallin, A., Blennow, E., & Nordenskjöld, M. (2003). Cryptic subtelomeric 6p deletion in a girl with congenital malformations and severe language impairment. European Journal of Human Genetics, 11(1), 89-92. https://doi.org/10.1038/sj.ejhg.5200907
Arcot Sadagopan, K., Liu, G. T., Capasso, J. E., Wuthisiri, W., Keep, R. B., & Levin, A. V. (2015). Anirdia-like phenotype caused by 6p25 dosage aberrations. American Journal of Medical Genetics Part A, 167(3), 524-528. https://doi.org/10.1002/ajmg.a.36890
Atli, E. I., Gurkan, H., Atli, E., Vatansever, U., Acunas, B., & Mail, C. (2020). De novo subtelomeric 6p25.3 deletion with duplication of 6q23.3-q27: Genotype-phenotype correlation. Journal of Pediatric Genetics, 9(1), 32-39. https://doi.org/10.1055/s-0039-1694703
Balasubramanian, M., Smith, K., Williams, S., Griffiths, P., Parker, M., & Mordekar, S. (2015). Tigroid pattern of cerebral white matter involvement in chromosome 6p25 deletion syndrome with concomitant 5p15 duplication. Journal of Pediatric Genetics, 01(4), 247-252. https://doi.org/10.3233/PGE-12040
Beby, F., Des Portes, V., Till, M., Mottolese, C., & Denis, P. (2012). Chromosome 6p25 deletion syndrome: Report of a case with optic disc coloboma and review of published ophthalmic findings. Ophthalmic Genetics, 33(4), 240-248. https://doi.org/10.3109/13816810.2012.675396
Bedoyan, J. K., Lesperance, M. M., Ackley, T., Iyer, R. K., Innis, J. W., & Misra, V. K. (2011). A complex 6p25 rearrangement in a child with multiple epiphyseal dysplasia. American Journal of Medical Genetics Part A, 155(1), 154-163. https://doi.org/10.1002/ajmg.a.33751
Caluseriu, O., Mirza, G., Ragoussis, J., Chow, E. W. C., MacCrimmon, D., & Bassett, A. S. (2006). Schizophrenia in an adult with 6p25 deletion syndrome. American Journal of Medical Genetics Part A, 140A(11), 1208-1213. https://doi.org/10.1002/ajmg.a.31222
Cellini, E., Disciglio, V., Novara, F., Barkovich, J. A., Mencarelli, M. A., Hayek, J., Renieri, A., Zuffardi, O., & Guerrini, R. (2012). Periventricular heterotopia with white matter abnormalities associated with 6p25 deletion. American Journal of Medical Genetics Part A, 158A(7), 1793-1797. https://doi.org/10.1002/ajmg.a.35416
Corona-Rivera, J. R., Corona-Rivera, A., Zepeda-Romero, L. C., Rios-Flores, I. M., Rivera-Vargas, J., Orozco-Vela, M., Santana-Bejarano, U. F., Torres-Anguiano, E., Pinto-Cardoso, M., David, D., & Bobadilla-Morales, L. (2019). Ring chromosome 6 in a child with anterior segment dysgenesis and review of its overlap with other FOXC1 deletion phenotypes. Congenital Anomalies, 59(5), 174-178. https://doi.org/10.1111/cga.12309
Davies, A. F., Mirza, G., Sekhon, G., Turnpenny, P., Leroy, F., Speleman, F., Law, C., van Regemorter, N., Vamos, E., Flinter, F., & Ragoussis, J. (1999). Delineation of two distinct 6p deletion syndromes. Human Genetics, 104(1), 64-72. https://doi.org/10.1007/s004390050911
de Vos, I. J. H. M., Stegmann, A. P. A., Webers, C. A. B., & Stumpel, C. T. R. M. (2017). The 6p25 deletion syndrome: An update on a rare neurocristopathy. Ophthalmic Genetics, 38(2), 101-107. https://doi.org/10.3109/13816810.2016.1164191
De Vries, B. B. A. (2003). Telomeres: A diagnosis at the end of the chromosomes. Journal of Medical Genetics, 40(6), 385-398. https://doi.org/10.1136/jmg.40.6.385
Delahaye, A., Khung-Savatovsky, S., Aboura, A., Guimiot, F., Drunat, S., Alessandri, J.-L., Gérard, M., Bitoun, P., Boumendil, J., Robin, S., Huel, C., Guilherme, R., Serero, S., Gressens, P., Elion, J., Verloes, A., Benzacken, B., Delezoide, A.-L., & Pipiras, E. (2012). Pre- and postnatal phenotype of 6p25 deletions involving the FOXC1 gene. American Journal of Medical Genetics Part A, 158A(10), 2430-2438. https://doi.org/10.1002/ajmg.a.35548
DeScipio, C., Schneider, L., Young, T. L., Wasserman, N., Yaeger, D., Lu, F., Wheeler, P. G., Williams, M. S., Bason, L., Jukofsky, L., Menon, A., Geschwindt, R., Chudley, A. E., Saraiva, J., Schinzel, A. A. G. L., Guichet, A., Dobyns, W. E., Toutain, A., Spinner, N. B., & Krantz, I. D. (2005). Subtelomeric deletions of chromosome 6p: Molecular and cytogenetic characterization of three new cases with phenotypic overlap with Ritscher-Schinzel (3C) syndrome. American Journal of Medical Genetics Part A, 134A(1), 3-11. https://doi.org/10.1002/ajmg.a.30573
D'haene, B., Meire, F., Claerhout, I., Kroes, H. Y., Plomp, A., Arens, Y. H., de Ravel, T., Casteels, I., De Jaegere, S., Hooghe, S., Wuyts, W., van den Ende, J., Roulez, F., Veenstra-Knol, H. E., Oldenburg, R. A., Giltay, J., Verheij, J. B. G. M., de Faber, J.-T., Menten, B., … De Baere, E. (2011). Expanding the Spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations. Investigative Opthalmology & Visual Science, 52(1), 324-333. https://doi.org/10.1167/iovs.10-5309
Fan, S., Lee, N., & Lin, C. (2020). Novel phenotype of 6p25 deletion syndrome presenting juvenile parkinsonism and brain calcification. Movement Disorders, 35(8), 1457-1462. https://doi.org/10.1002/mds.28079
Gould, D. B., Jaafar, M. S., Addison, M. K., Munier, F., Ritch, R., MacDonald, I. M., & Walter, M. A. (2004). Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment. BMC Medical Genetics, 5(1), 17. https://doi.org/10.1186/1471-2350-5-17
Gripp, K. W., Hopkins, E., Jenny, K., Thacker, D., & Salvin, J. (2013). Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation. American Journal of Medical Genetics Part A, 161(1), 114-119. https://doi.org/10.1002/ajmg.a.35697
Hosono, K., Kawase, K., Kurata, K., Niimi, Y., Saitsu, H., Minoshima, S., Ohnishi, H., Yamamoto, T., Hikoya, A., Tachibana, N., Fukao, T., Yamamoto, T., & Hotta, Y. (2020). A case of childhood glaucoma with a combined partial monosomy 6p25 and partial trisomy 18p11 due to an unbalanced translocation. Ophthalmic Genetics, 41(2), 175-182. https://doi.org/10.1080/13816810.2020.1744019
Kannu, P., Oei, P., Slater, H. R., Khammy, O., & Aftimos, S. (2006). Epiphyseal dysplasia and other skeletal anomalies in a patient with the 6p25 microdeletion syndrome. American Journal of Medical Genetics Part A, 140A(18), 1955-1959. https://doi.org/10.1002/ajmg.a.31411
Kapoor, S., Banerjee Mukherjee, S., Shroff, D., Arora, R., Mukhopadhyay, D., Ghosh, A., Mukhopadhyay, M., Narayan, J. P., Garg, P., Pareek, G., Narayan, S., Thakur, S., Flanagan, S. E., Ellard, S., Verma, I. C., Mondal, R., Nandi, M., Tiwari, A., & Chakravorti, S. (2011). Case reports. Indian Pediatrics, 48(9), 727-736. https://doi.org/10.1007/s13312-011-0108-8
Law, C. J., Fisher, A. M., & Temple, I. K. (1998). Distal 6p deletion syndrome: A report of a case with anterior chamber eye anomaly and review of published reports. Journal of Medical Genetics, 35(8), 685-689. https://doi.org/10.1136/jmg.35.8.685
Le Caignec, C., De Mas, P., Vincent, M.-C., Bocéno, M., Bourrouillou, G., Rival, J.-M., & David, A. (2005). Subtelomeric 6p deletion: Clinical, FISH, and array CGH characterization of two cases: Subtelomeric 6p deletion. American Journal of Medical Genetics Part A, 132A(2), 175-180. https://doi.org/10.1002/ajmg.a.30409
Lehmann, O. J., Ebenezer, N. D., Ekong, R., Ocaka, L., Mungall, A. J., Fraser, S., McGill, J. I., Hitchings, R. A., Khaw, P. T., Sowden, J. C., Povey, S., Walter, M. A., Bhattacharya, S. S., & Jordan, T. (2002). Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Investigative Ophthalmology & Visual Science, 43(6), 1843-1849.
Lin, R. J., Cherry, A. M., Chen, K. C., Lyons, M., Hoyme, H. E., & Hudgins, L. (2005). Terminal deletion of 6p results in a recognizable phenotype. American Journal of Medical Genetics Part A, 136A(2), 162-168. https://doi.org/10.1002/ajmg.a.30784
Linhares, N. D., Svartman, M., Rodrigues, T. C., Rosenberg, C., & Valadares, E. R. (2015). Subtelomeric 6p25 deletion/duplication: Report of a patient with new clinical findings and genotype-phenotype correlations. European Journal of Medical Genetics, 58(5), 310-318. https://doi.org/10.1016/j.ejmg.2015.02.011
Lukusa, T., & Fryns, J. P. (2010). Pure de novo 17q25.3 micro duplication characterized by micro array CGH in a dysmorphic infant with growth retardation, developmental delay and distal arthrogryposis. Genetic Counseling (Geneva, Switzerland), 21(1), 25-34.
Maclean, K., Smith, J., Heaps, L. S., Chia, N., Williams, R., Peters, G. B., Onikul, E., McCrossin, T., Lehmann, O. J., & Adès, L. C. (2005). Axenfeld-Rieger malformation and distinctive facial features: Clues to a recognizable 6p25 microdeletion syndrome. American Journal of Medical Genetics Part A, 132A(4), 381-385. https://doi.org/10.1002/ajmg.a.30274
Martinet, D., Filges, I., Besuchet Schmutz, N., Morris, M. A., Gaide, A.-C., Dahoun, S., Bottani, A., Addor, M.-C., Antonarakis, S. E., Beckmann, J. S., & Béna, F. (2008). Subtelomeric 6p deletion: Clinical and array-CGH characterization in two patients. American Journal of Medical Genetics Part A, 146A(16), 2094-2102. https://doi.org/10.1002/ajmg.a.32414
Martinez-Glez, V., Lorda-Sanchez, I., Ramirez, J. M., Ruiz-Barnes, P., Rodriguez de Alba, M., Diego-Alvarez, D., Ramos, C., Searby, C. C., Nishimura, D. Y., & Ayuso, C. (2007). Clinical presentation of a variant of Axenfeld-Rieger syndrome associated with subtelomeric 6p deletion. European Journal of Medical Genetics, 50(2), 120-127. https://doi.org/10.1016/j.ejmg.2006.10.005
Mirza, G., Williams, R. R., Mohammed, S., Clark, R., Newbury-Ecob, R., Baldinger, S., Flinter, F., & Ragoussis, J. (2004). Refined genotype-phenotype correlations in cases of chromosome 6p deletion syndromes. European Journal of Human Genetics, 12(9), 718-728. https://doi.org/10.1038/sj.ejhg.5201194
Nakane, T., Kousuke, N., Sonoko, H., Yuko, K., Sato, H., Kubota, T., & Sugita, K. (2013). 6p subtelomere deletion with congenital glaucoma, severe mental retardation, and growth impairment: 6p deletion. Pediatrics International, 55(3), 376-381. https://doi.org/10.1111/j.1442-200X.2012.03729.x
Nishimura, D. Y., Swiderski, R. E., Alward, W. L. M., Searby, C. C., Patil, S. R., Bennet, S. R., Kanis, A. B., Gastier, J. M., Stone, E. M., & Sheffield, V. C. (1998). The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nature Genetics, 19(2), 140-147. https://doi.org/10.1038/493
Pavone, P., Marino, S. D., Corsello, G., Ruggieri, M., Chiodo, D. C., Marino, S., & Falsaperla, R. (2019). Cerebral white matter lesions and dysmorphisms: Signs suggestive of 6p25 deletion syndrome-Literature review. Journal of Pediatric Genetics, 8(4), 205-211. https://doi.org/10.1055/s-0039-1694015
Piccione, M., Antona, R., Salzano, E., Cavani, S., Malacarne, M., Morreale Bubella, R., Pierluigi, M., Viaggi, C. D., & Corsello, G. (2012). Array-CGH and clinical characterization in a patient with subtelomeric 6p deletion without ocular dysgenesis. American Journal of Medical Genetics Part A, 158A(1), 150-154. https://doi.org/10.1002/ajmg.a.34308
Reid, C. S., Stamberg, J., & Phillips, J. A. (1983). Monosomy for distal segment 6p: Clinical description and use in localizing a region important for expression of Hageman factor. Pediatric Research, 17, A217.
Reis, L. M., Tyler, R. C., Volkmann Kloss, B. A., Schilter, K. F., Levin, A. V., Lowry, R. B., Zwijnenburg, P. J. G., Stroh, E., Broeckel, U., Murray, J. C., & Semina, E. V. (2012). PITX2 and FOXC1 spectrum of mutations in ocular syndromes. European Journal of Human Genetics, 20(12), 1224-1233. https://doi.org/10.1038/ejhg.2012.80
Strungaru, M. H., Dinu, I., & Walter, M. A. (2007). Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Investigative Opthalmology & Visual Science, 48(1), 228-237. https://doi.org/10.1167/iovs.06-0472
Tonoki, H., Harada, N., Shimokawa, O., Yosozumi, A., Monzaki, K., Satoh, K., Kosaki, R., Sato, A., Matsumoto, N., & Iizuka, S. (2011). Axenfeld-Rieger anomaly and Axenfeld-Rieger syndrome: Clinical, molecular-cytogenetic, and DNA array analyses of three patients with chromosomal defects at 6p25. American Journal of Medical Genetics Part A, 155(12), 2925-2932. https://doi.org/10.1002/ajmg.a.33858
Tümer, Z., & Bach-Holm, D. (2009). Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. European Journal of Human Genetics, 17(12), 1527-1539. https://doi.org/10.1038/ejhg.2009.93
van der Knaap, M. S., Kriek, M., Overweg-Plandsoen, W. C. G., Hansson, K. B., Madan, K., Starreveld, J. S., Schotman-Schram, P., Barkhof, F., & Lesnik Oberstein, S. A. M. J. (2006). Cerebral white matter abnormalities in 6p25 deletion syndrome. American Journal of Neuroradiology, 27(3), 586-588.
Vernon, H. J., Bytyci Telegrafi, A., Batista, D., Owegi, M., & Leigh, R. (2013). 6p25 microdeletion: White matter abnormalities in an adult patient. American Journal of Medical Genetics Part A, 161(7), 1686-1689. https://doi.org/10.1002/ajmg.a.35937
Weegerink, N. J. D., Swinnen, F. K. R., Vanakker, O. M., Casselman, J. W., & Dhooge, I. J. M. (2016). Phenotype of a Belgian family with 6p25 deletion syndrome. Annals of Otology, Rhinology & Laryngology, 125(9), 734-745. https://doi.org/10.1177/0003489416650687
Zurcher, V. L., Golden, W. L., & Zinn, A. B. (1990). Distal deletion of the short arm of chromosome 6. American Journal of Medical Genetics, 35(2), 261-265. https://doi.org/10.1002/ajmg.1320350223