13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia.

ABSTRACT

We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopathies, such as Costello syndrome, present a phenotype with (relative) macrocephaly as perinatal features. However, prenatal-onset macroglossia are generally absent in this syndrome but rather suggestive of the Beckwith-Wiedemann syndrome for which molecular testing were negative. Phenotype-genotype correlation with patients from DECIPHER defines NDFIP2 and SPRY2 as a possible candidate genes for a RASopathy potentially responsible for the clinical features in the fetus. Finally, this original case of 13q31.1 microdeletion underlines the importance of array-CGH in prenatal diagnosis with sonographic signs such as macroglossia and/or macrocephaly. In this case, genetic investigation should be not limited to the search of well-known genetic causes and other genomic microdeletions should be considered as alternative diagnoses for macroglossia.