A Unique syndrome with facial, cranial, dental and skeletal features: possible relationship to maternal chikungunya exposure or an unidentified genetic cause?

Abstract

BACKGROUND:Six children from the western province of Sri Lanka, born between June 2007 and November 2008 have presented with a unique phenotype comprising distinctive facial features, skeletal abnormalities and variable intellectual disability. In four children the mother reported a clinical history of chikungunya infection (CHKV) during their first trimester. OBJECTIVE: • Describe the clinical and demographic features of affected cases • Identify a genetic basis using whole exome sequencing (WES) DESIGN, SETTING AND METHOD: Cases were recruited following informed consent from parents. Blood taken for DNA extraction and WES performed using the lllumina HiSeq 2500 platform. Reads were aligned to the human reference sequence hg19 and analysed using bioinformatics software. RESULTS: Four cases were females. Five were Sinhalese, one Tamil. None had parental consanguinity. Four mothers reported first trimester CHKV infection. Distinctive facial features (pinched face, downslanting eyes, turri-brachvcephalv, open mouth, lip retraction, V shaped dental arches and high mandibular angles), restriction of joint movements (small and large joints) and variable developmental delay were present. Review by a panel of experts revealed no syndrome diagnosis WES analysis on five cases did not identify a homozygous or compound heterozygous recessive or de novo dominant mutation of an autosomal gene. CONCLUSIONS: WES analysis did not identify a homozygous or compound heterozygous recessive or de novo dominant mutation of an autosomal gene.