Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae. Issue 11 (28th September 2017)

• Record Type: Journal Article
• Authors: Eppley, Sarah; Hopkin, Robert J.; Mendelsohn, Bryce; Slavotinek, Anne M.
• Is Part Of: American journal of medical genetics. Volume 173:Issue 11(2017)
• Page Start: 3075
• Page End: 3081
• Publication Date: 2017-09-28
• Subjects: chromosome breakage syndrome -- cohesinopathy -- DDX11 -- genomic instability -- Warsaw Breakage Syndrome (WABS); Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.38382
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11 . After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants—c.1523T>G, predicting (p.Leu508Arg) and c.1949‐1G>A (IVS19‐1G>A), that were confirmed with Sanger sequencing in both affected individuals. DDX11 encodes an iron‐sulfur‐containing DNA helicase, and mutations in this gene have been reported in the five WABS cases previously identified to date. The sisters reported here display the distinguishing clinical features of WABS: pre‐ and post‐natal growth restriction, microcephaly, intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphic features. In addition, our cases had early menarche at 8 and 10 years of age, bilateral small thumbs, and the younger, more severely affected sister had small fibulae. These findings broaden the WABS phenotype and the limb malformations demonstrate further clinical overlap with Fanconi anemia and other cohesinopathies, such as Roberts Syndrome.