Craniofacial Disorders



Craniofacial Disorders can be caused by alterations in many different genes. This P080-C1 probemix contains probes for the FGFR1, FGFR2, FGFR3, TWIST1, MSX2, ALX1, ALX3, ALX4, EFNB1 and RUNX2 genes.


The FGFR1 (8p11.23; 18 exons), FGFR2 (10q26.13; 21 exons) and FGFR3 (4p16.3; 19 exons) genes encode fibroblast growth factor receptors and cause a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 cause most craniosynostosis. The dwarfing syndromes are often associated with FGFR3 mutations. Deletion of the TWIST1 gene (7p21.1; 2 exons) is the cause of disease in an estimated 11 % of Saethre-Chotzen syndrome patients. Included is also a probe for the TWISTNB (TWIST nearby) gene located at a distance of ~500 kb from TWIST. Large deletions of the TWIST region often result in mental retardation. Dosage of the MSX2 gene (5q35.2; 2 exons) is critical for human skull development. Enlarged parietal foramina and craniosynostosis can result, respectively, from loss and gain of activity in an MSX2 pathway of calvarial osteogenic differentiation.


Mutations in ALX4 (11p11.2; 4 exons) can result in parietal foramina as well as craniosynostosis (premature fusion of the cranial sutures). Potocki-Shaffer syndrome, also known as the proximal 11p deletion syndrome, is a contiguous gene syndrome caused by deletion of this 11p13-p11 region. Mutations in the ALX3 gene (1p13.3; 4 exons) can result in frontonasal dysplasia. The ALX1 gene (CART1; 12q21.31; 4 exons) is known to be essential for normal skull bone development, null mice are born with severe craniofacial defects such as a lacking cranium. Defects in the RUNX2 gene (6p21.1; 9 exons) cause the dominant disorder cleidocranial dysplasia. Loss-of-function mutations in the EFNB1 gene (Xq13.1; 5 exons) cause craniofrontonasal syndrome. In addition, nine reference probes are included, detecting several different autosomal chromosomal locations.