Mandibulofacial dysostosis, microtia, and limb anomalies in a newborn: a new form of acrofacial dysostosis syndrome?

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders involving craniofacial dysostosis and limb anomalies. Depending on the type of limb defects, two major groups have been defined: Nager syndrome with predominant preaxial anomalies and Miller syndrome with postaxial malformations. Genomic copy number variation, a common type of genomic variability, can influence gene expression by disrupting coding sequences, perturbing long-range gene regulation, or altering gene dosage, and these effects could contribute to phenotypic variations or disease risk. We present a distinct AFD case with mandibulofacial dysostosis, microtia and limb malformations but without limb defects, which may represent a new form of AFD. To investigate the etiology of the phenotype, whole genomic high-resolution array comparative genomic hybridization analysis was carried out, revealing two cryptic duplications, 1p36.33 and 1q21.3-q22 duplications. Two genes, VWA1 and PYGO2, contained in the two duplications, respectively, are likely to be the candidate genes for the phenotype of our patient.