Frontonasal dysplasia (FND) is a heterogeneous group of disorders characterized by hypertelorism, telecanthus, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella and smooth philtrum.
SIX1 and SIX2 encode closely related transcription factors of which disruptions have been associated with distinct craniofacial syndromes, with mutations in SIX1 associated with branchiootic syndrome 3 (BOS3) and heterozygous deletions of SIX2 associated with frontonasal dysplasia defects.
Although the patient reported herein manifests some overlapping features of FND and PPS, it is likely that the observed phenotype maybe due to a second unidentified mutation in the ALX4 gene.
Although the patient reported herein manifests some overlapping features of FND and PPS, it is likely that the observed phenotype maybe due to a second unidentified mutation in the ALX4 gene.
Children/adolescents with FND had excessive theta and delta power in electrode clusters corresponding to the DMN-both anteriorly (dorsomedial prefrontal cortex [dmFPC]) and posteriorly (posterior cingulate cortex [PCC], precuneus, and lateral parietal cortex)-and in the premotor/supplementary motor area (SMA) region.
Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature.
Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.
Genome scan using 250k Nsp1 array followed by exome and Sanger sequence analysis revealed a novel homozygous nonsense variant (c.604C>T, p.Gln202*) in the ALX3 gene resulting in frontorhiny in the family.
Genome scan using 250k Nsp1 array followed by exome and Sanger sequence analysis revealed a novel homozygous nonsense variant (c.604C>T, p.Gln202*) in the ALX3 gene resulting in frontorhiny in the family.
Here, we describe a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions (p.Glu117Val and p.Glu117Gly) at a highly conserved glutamic acid residue located in the basic DNA binding domain of TWIST1, in two subjects with frontonasal dysplasia and additional malformations.