Warsaw Breakage Syndrome – A further report, emphasising cutaneous findings

Abstract

We report a new case of Warsaw Breakage syndrome (WABS) with 2 confirmed mutations in DDX11. Like the previous reported cases [Capo-Chichi et al., 2012; Van der Lelij et al., 2010], there was evidence of pre- and postnatal growth retardation, severe microcephaly, intellectual disability and facial dysmorphism. The patient had sensorineural hearing loss with evidence of bilateral hypoplastic cochleas on imaging, another feature which has been reported in the previous cases of WABS. In our case the patient exhibited a chronic rash of livedo reticularis with telangiectasia on her legs. Abnormally pigmented lesions and cutis mamorata were reported in the original WABS case.

Introduction

We report another case of Warsaw Breakage Syndrome (WABS). WABS is a cohesinopathy associated with mutations in the iron-sulphur-containing DNA helicase DDX11 (ChlR1). The syndrome is associated with abnormalities in the cohesion of sister chromatids and also sensitivity to chemicals which induce replication stress, thus the syndrome is a combination of the cytogenetic features seen in both Roberts Syndrome and Fanconi anaemia. [Capo-Chichi et al., 2012, Van der Lelij et al., 2010] The syndrome was first in described in 2010 in a male individual with heterozygous mutations in DDX11. Since then, a further three siblings with consanguineous parents were identified as having a novel homozygous mutation in DDX11. Our case shares similar phenotypic features to the previous reported cases including pre- and postnatal growth retardation, severe microcephaly, intellectual disability, facial dysmorphism and hearing loss due to cochlea abnormalities. In addition to this our case also had a chronic petechial rash. Skin lesions were also reported in the original WABS case suggesting that cutaneous findings may be another feature of the phenotype.