Ocular manifestations in a cohort of 43 patients with KBG syndrome.
clinical genetics
genetic testing
medical genetics
ophthalmology
refractive errors
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:
14 Nov 2023
14 Nov 2023
Historique:
revised:
24
10
2023
received:
05
06
2023
accepted:
05
11
2023
medline:
15
11
2023
pubmed:
15
11
2023
entrez:
15
11
2023
Statut:
aheadofprint
Résumé
Ophthalmological conditions are underreported in patients with KBG syndrome, which is classically described as presenting with dental, developmental, intellectual, skeletal, and craniofacial abnormalities. This study analyzed the prevalence of four ophthalmological conditions (strabismus, astigmatism, myopia, hyperopia) in 43 patients with KBG syndrome carrying variants in ANKRD11 or deletions in 16q24.3 and compared it to the literature. Forty-three patients were recruited via self-referral or a private Facebook group hosted by the KBG Foundation, with 40 of them having pathogenic or likely pathogenic variants. Virtual interviews were conducted to collect a comprehensive medical history verified by medical records. From these records, data analysis was performed to calculate the prevalence of ophthalmological conditions. Out of the 40 participants with pathogenic or likely pathogenic variants, strabismus was reported in 9 (22.5%) participants, while astigmatism, myopia, and hyperopia were reported in 11 (27.5%), 6 (15.0%), and 8 (20.0%) participants, respectively. Other reported conditions include anisometropia, amblyopia, and nystagmus. When compared to the literature, the prevalence of strabismus and refractive errors is higher than other studies. However, more research is needed to determine if variants in ANKRD11 play a role in abnormal development of the visual system. In patients with established KBG syndrome, screening for misalignment or refractive errors should be done, as interventions in patients with these conditions can improve functioning and quality of life.
Identifiants
pubmed: 37964495
doi: 10.1002/ajmg.a.63473
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : KBG Syndrome Foundation
Organisme : the New York State Office for People With Developmental Disabilities
Informations de copyright
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
Références
Alfieri, P., Demaria, F., Licchelli, S., Santonastaso, O., Caciolo, C., Digilio, M. C., Sinibaldi, L., Leoni, C., Gnazzo, M., Tartaglia, M., Pasqualetti, P., & Vicari, S. (2019). Obsessive compulsive symptoms and psychopathological profile in children and adolescents with KBG syndrome. Brain Sciences, 9, 313.
Ashraf, T., Harrison, M., & Irving, M. (2022). Ear lobe creases: A novel phenotypic feature in KBG syndrome. American Journal of Medical Genetics. Part A, 188, 1618-1622.
Auconi, M., Serino, D., Digilio, M. C., Gnazzo, M., Conti, M., Vigevano, F., & Fusco, L. (2022). Epilepsy in KBG syndrome. Developmental Medicine and Child Neurology, 65(5), 712-720.
Bowen, M. E., & Attardi, L. D. (2019). The role of p53 in developmental syndromes. Journal of Molecular Cell Biology, 11, 200-211.
Brancati, F., Sarkozy, A., & Dallapiccola, B. (2006). KBG syndrome. Orphanet Journal of Rare Diseases, 1, 50.
Braverman, R. (2007). Diagnosis and treatment of refractive errors in the pediatric population. Current Opinion in Ophthalmology, 18, 379-383.
Chen, J., Xia, Z., Zhou, Y., Ma, X., Wang, X., & Guo, Q. (2021). A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome. BMC Medical Genomics, 14, 68.
Choi, Y., Choi, J., Do, H., Hwang, S., Seo, G. H., Choi, I. H., Keum, C., Choi, J.-H., Kang, M., Kim, G.-H., Yoo, H.-W., & Lee, B. H. (2023). KBG syndrome: Clinical features and molecular findings in seven unrelated Korean families with a review of the literature. Molecular Genetics & Genomic Medicine, 11, e2127.
Chopra, M., McEntagart, M., Clayton-Smith, J., Platzer, K., Shukla, A., Girisha, K. M., Kaur, A., Kaur, P., Pfundt, R., Veenstra-Knol, H., Mancini, G. M. S., Cappuccio, G., Brunetti-Pierri, N., Kortüm, F., Hempel, M., Denecke, J., Lehman, A., CAUSES Study, Kleefstra, T., … Gordon, C. T. (2021). Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism. American Journal of Human Genetics, 108, 1138-1150.
Cucco, F., Sarogni, P., Rossato, S., Alpa, M., Patimo, A., Latorre, A., Magnani, C., Puisac, B., Ramos, F. J., Pié, J., & Musio, A. (2020). Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome. American Journal of Medical Genetics. Part A, 182, 1690-1696.
Digilio, M. C., Calcagni, G., Gnazzo, M., Versacci, P., Dentici, M. L., Capolino, R., Sinibaldi, L., Baban, A., Putotto, C., Alfieri, P., Unolt, M., Lepri, F. R., Alesi, V., Genovese, S., Novelli, A., Marino, B., & Dallapiccola, B. (2022). Congenital heart defects in molecularly confirmed KBG syndrome patients. American Journal of Medical Genetics. Part A, 188, 1149-1159.
Fozailoff, A., Tarczy-Hornoch, K., Cotter, S., Wen, G., Lin, J., Borchert, M., Azen, S., Varma, R., & Writing Committee for the MEPEDS Study Group. (2011). Prevalence of astigmatism in 6- to 72-month-old African American and Hispanic children: The Multi-Ethnic Pediatric Eye Disease Study. Ophthalmology, 118, 284-293.
Friedman, D. S., Repka, M. X., Katz, J., Giordano, L., Ibironke, J., Hawse, P., & Tielsch, J. M. (2009). Prevalence of amblyopia and strabismus in white and African American children aged 6 through 71 months the Baltimore pediatric eye disease study. Ophthalmology, 116, 2128-2134.e2.
Gnazzo, M., Lepri, F. R., Dentici, M. L., Capolino, R., Pisaneschi, E., Agolini, E., Rinelli, M., Alesi, V., Versacci, P., Genovese, S., Cesario, C., Sinibaldi, L., Baban, A., Bartuli, A., Marino, B., Cappa, M., Dallapiccola, B., Novelli, A., & Digilio, M. C. (2020). KBG syndrome: Common and uncommon clinical features based on 31 new patients. American Journal of Medical Genetics. Part A, 182, 1073-1083.
Helveston, E. M. (2010). Understanding, detecting, and managing strabismus. Community Eye Health., 23, 12-14.
Herrmann, J., Pallister, P. D., Tiddy, W., & Opitz, J. M. (1975). The KBG syndrome-a syndrome of short stature, characteristic facies, mental retardation, macrodontia and skeletal anomalies. Birth Defects Original Article Series, 11, 7-18.
Kleinstein, R. N., Jones, L. A., Hullett, S., Kwon, S., Lee, R. J., Friedman, N. E., Manny, R. E., Mutti, D. O., Yu, J. A., Zadnik, K., & Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study Group. (1960). Refractive error and ethnicity in children. Archieves of Ophthalmology (Chicago IL), 2003(121), 1141-1147.
Libianto, R., Wu, K. H., Devery, S., Eisman, J. A., & Center, J. R. (2019). KBG syndrome presenting with brachydactyly type E. Bone, 123, 18-22.
Low, K., Ashraf, T., Canham, N., Clayton-Smith, J., Deshpande, C., Donaldson, A., Fisher, R., Flinter, F., Foulds, N., Fryer, A., Gibson, K., Hayes, I., Hills, A., Holder, S., Irving, M., Joss, S., Kivuva, E., Lachlan, K., Magee, A., … Smithson, S. (2016). Clinical and genetic aspects of KBG syndrome. American Journal of Medical Genetics. Part A, 170, 2835-2846.
Mayro, E. L., Hark, L. A., Shiuey, E., Pond, M., Siam, L., Hill-Bennett, T., Tran, J., Khanna, N., Silverstein, M., Donaghy, J., Zhan, T., Murchison, A. P., & Levin, A. V. (2018). Prevalence of uncorrected refractive errors among school-age children in the School District of Philadelphia. Journal of AAPOS: The Official Publication of the American Association of Pediatric Ophthalmology and Strabismus, 22, 214-217.e2.
McKean-Cowdin, R., Cotter, S. A., Tarczy-Hornoch, K., Wen, G., Kim, J., Borchert, M., Varma, R., & Multi-Ethnic Pediatric Eye Disease Study Group. (2013). Prevalence of amblyopia or strabismus in asian and non-Hispanic white preschool children: Multi-ethnic pediatric eye disease study. Ophthalmology, 120, 2117-2124.
Multi-ethnic Pediatric Eye Disease Study Group. (2008). Prevalence of amblyopia and strabismus in African American and Hispanic children ages 6 to 72 months the multi-ethnic pediatric eye disease study. Ophthalmology, 115, 1229-1236.e1.
Multi-Ethnic Pediatric Eye Disease Study Group. (2010). Prevalence of myopia and hyperopia in 6- to 72-month-old African American and Hispanic children: The multi-ethnic pediatric eye disease study. Ophthalmology, 117, 140-147.e3.
Neilsen, P. M., Cheney, K. M., Li, C.-W., Chen, J. D., Cawrse, J. E., Schulz, R. B., Powell, J. A., Kumar, R., & Callen, D. F. (2008). Identification of ANKRD11 as a p53 coactivator. Journal of Cell Science, 121, 3541-3552.
Nizette, G., & Duchesne, B. (2021). Ophthalmologic signs in a KBG syndrome, a rare genetic disease. Revue Médicale de Liège, 76, 625-628.
Novara, F., Rinaldi, B., Sisodiya, S. M., Coppola, A., Giglio, S., Stanzial, F., Benedicenti, F., Donaldson, A., Andrieux, J., Stapleton, R., Weber, A., Reho, P., van Ravenswaaij-Arts, C., Kerstjens-Frederikse, W. S., Vermeesch, J. R., Devriendt, K., Bacino, C. A., Delahaye, A., Maas, S. M., … Zuffardi, O. (2017). Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases. European Journal of Human Genetics: EJHG, 25, 694-701.
Ockeloen, C. W., Willemsen, M. H., de Munnik, S., van Bon, B. W. M., de Leeuw, N., Verrips, A., Kant, S. G., Jones, E. A., Brunner, H. G., van Loon, R. L. E., Smeets, E. E. J., van Haelst, M. M., van Haaften, G., Nordgren, A., Malmgren, H., Grigelioniene, G., Vermeer, S., Louro, P., Ramos, L., … Kleefstra, T. (2015). Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations. European Journal of Human Genetics: EJHG, 23, 1176-1185.
Repka, M. X., Lum, F., & Burugapalli, B. (2018). Strabismus, strabismus surgery, and reoperation rate in the United States: Analysis from the IRIS registry. Ophthalmology, 125, 1646-1653.
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H. L., & ACMG Laboratory Quality Assurance Committee. (2015). 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. Genetics in Medicne: Official Journal of the American College of Medical Genetics, 17, 405-424.
Sirmaci, A., Spiliopoulos, M., Brancati, F., Powell, E., Duman, D., Abrams, A., Bademci, G., Agolini, E., Guo, S., Konuk, B., Kavaz, A., Blanton, S., Digilio, M. C., Dallapiccola, B., Young, J., Zuchner, S., & Tekin, M. (2011). Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia. American Journal of Human Genetics, 89, 289-294.
Skjei, K. L., Martin, M. M., & Slavotinek, A. M. (2007). KBG syndrome: Report of twins, neurological characteristics, and delineation of diagnostic criteria. American Journal of Medical Genetics. Part A, 143A, 292-300.
Sveden, A., Gordon, C. T., Amiel, J., & Chopra, M. (1993). ANKRD17-related neurodevelopmental syndrome. In M. P. Adam, J. Feldman, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, L. J. H. Bean, K. W. Gripp, A. Amemiya (Eds.), GeneReviews® [Internet]. Seattle (WA): University of Washington.
Swols, D., Foster, J., & Tekin, M. (2017). KBG syndrome. Orphanet Journal of Rare Diseases, 12, 183.
Wen, G., Tarczy-Hornoch, K., McKean-Cowdin, R., Cotter, S. A., Borchert, M., Lin, J., Kim, J., Varma, R., & Multi-Ethnic Pediatric Eye Disease Study Group. (2013). Prevalence of myopia, hyperopia and astigmatism in non-Hispanic White and Asian Children: Multi-Ethnic Pediatric Eye Disease Study. Ophthalmology, 120, 2109-2116.
Zhang, A., Yeung, P. L., Li, C.-W., Tsai, S.-C., Dinh, G. K., Wu, X., Li, H., & Chen, J. D. (2004). Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators. The Journal of Biological Chemistry, 279, 33799-33805.