Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants.

Autor: Cardoso LCA; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain., Parra A; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain., Gil CR; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain., Arias P; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain., Gallego N; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain., Romanelli V; Bionano Genomics, San Diego, CA 92121, USA., Kantaputra PN; Department of Orthodontics and Pediatric Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand., Lima L; Instituto Fernandes Figueira IFF/FIOCRUZ, Rio de Janeiro 22250-020, Brazil., Llerena Júnior JC; Instituto Fernandes Figueira IFF/FIOCRUZ, Rio de Janeiro 22250-020, Brazil., Arberas C; Hospital de Niños Dr. Ricardo Gutiérrez, Sección Genética Médica Gallo 1330, C1425EFD CABA, Argentina., Guillén-Navarro E; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; Sección Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, El Palmar, 30120 Murcia, Spain., Nevado J; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain., Spanish OverGrowth Registry Initiative; Spanish OverGrowth Registry Initiative, 28046 Madrid, Spain., Tenorio-Castano J; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain., Lapunzina P; INGEMM-Instituto de Genética Médica y Molecular, Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, 28046 Madrid, Spain.; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain.; ITHACA-European Reference Network, Hospital La Paz, 28046 Madrid, Spain.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Aug 05; Vol. 14 (15). Date of Electronic Publication: 2022 Aug 05.
DOI: 10.3390/cancers14153807
Abstrakt: Beckwith-Wiedemann syndrome spectrum (BWSp) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. Clinical features include overgrowth, macroglossia, neonatal hypoglycaemia, omphalocele, hemihyperplasia, cleft palate, and increased neoplasm incidence. The most common molecular defect observed is hypomethylation at the imprinting centre 2 (KCNQ1OT1:TSS DMR) in the maternal allele, which accounts for approximately 60% of cases, although CDKN1C pathogenic variants have been reported in 5-10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with pathogenic or likely pathogenic CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing, with special focus on the neoplasm incidence, given that there is scarce knowledge of this feature in CDKN1C -associated BWSp. In total, we evaluated 21 cases of BWSp with CDKN1C variants; 19 were classified as classical BWS according to the BWSp scoring classification by Brioude et al. One of our patients developed a mediastinal ganglioneuroma. Our study adds evidence that tumour development in patients with BWSp and CDKN1C variants is infrequent, but it is extremely relevant to the patient's follow-up and supports the high heterogeneity of BWSp clinical features associated with CDKN1C variants.
Databáze: MEDLINE
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