Phenotypic Overlap of Roberts and Baller-Gerold Syndromes in Two Patients With Craniosynostosis, Limb Reductions, and ESCO2 Mutations

Colombo E. A., Mutlu-Albayrak H., Shafeghati Y., Balasar M., Piard J., Gentilini D., ...Daha Fazla

FRONTIERS IN PEDIATRICS, cilt.7, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7
  • Basım Tarihi: 2019
  • Doi Numarası: 10.3389/fped.2019.00210
  • Dergi Adı: FRONTIERS IN PEDIATRICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Roberts syndrome, Baller-Gerold syndrome, RECQL4, ESCO2, patient management, genetic counseling, differential diagnosis, CHROMATID COHESION, RECQL4 MUTATIONS, READ ALIGNMENT, FANCONI-ANEMIA, SC PHOCOMELIA, SPECTRUM, DEFECT, ASSOCIATION, MISSENSE, CHILD
  • Ankara Üniversitesi Adresli: Evet

Özet

Baller-Gerold (BGS, MIM#218600) and Roberts (RBS, MIM#268300) syndromes are rare autosomal recessive disorders caused, respectively, by biallelic alterations in RECQL4 (MIM*603780) and ESCO2 (MIM*609353) genes. Common features are severe growth retardation, limbs shortening and craniofacial abnormalities which may include craniosynostosis. We aimed at unveiling the genetic lesions underpinning the phenotype of two unrelated children with a presumptive BGS diagnosis: patient 1 is a Turkish girl with short stature, microcephaly, craniosynostosis, seizures, intellectual disability, midface hemangioma, bilateral radial and thumb aplasia, tibial hypoplasia, and pes equinovarus. Patient 2 is an Iranian girl born to consanguineous parents with craniosynostosis, micrognathism, bilateral radial aplasia, thumbs, and foot deformity in the context of developmental delay. Upon negative RECQL4 test, whole exome sequencing (WES) analysis performed on the two trios led to the identification of two different ESCO2 homozygous inactivating variants: a previously described c.1131+1G> A transition in patient 1 and an unreported deletion, c.417de1, in patient 2, thus turning the diagnosis into Roberts syndrome. The occurrence of a Baller-Gerold phenotype in two unrelated patients that were ultimately diagnosed with RBS demonstrates the strength of WES in redefining the nosological landscape of rare congenital malformation syndromes, a premise to yield optimized patients management and family counseling.