Craniofacial Malformations 2011

Author: B. Wollnik
Submitted: Tuesday 6th of September 2011 09:27:38 AM
Submitted by: egf
Educational levels: expert, qc2, qc3


Craniofacial malformations affecting head and face are a primary cause of infant mortality and can result in severe functional, aesthetical, and social consequences for affected individuals and their families. Anomalies include ossification defects of facial and cranial bones, jaw deformities, malformed or missing teeth, ear anomalies, and facial asymmetries. Craniofacial anomalies - other than cleft lip and palate - occur in approximately 1 in every 2,000 newborns. A large variety of craniofacial malformations have been described in human, most of them are rare monogenic, non-syndromic or syndromic disorders. The latter are often associated with developmental disabilities, abnormalities of brain growth, hearing loss, eye and vision disturbances, and major functional problems of breathing, chewing, swallowing or speech. Most often, these malformations require interdisciplinary medical care involving many clinical specialities for diagnosis, counselling, and therapy. In order to improve patient care and therapeutic strategies, it is essential to (i) further understand the fundamental and complex biological processes underlying craniofacial development, (ii) to elucidate conserved molecular pathways during development, (iii) and to identify the molecular and pathogenic mechanisms of these disorders. Three years ago, we established the CRANIRARE consortium aiming to use an interdisciplinary and transnational approach to address the major items mentioned above essential for improved patient care. The talk will highlight the importance of collaborative work in rare diseases and show several examples of successful gene identification studies from the CRANIRARE consortium, which allowed us to elucidate new conserved molecular pathways and mechanisms important for biological processes of craniofacial development. For instance, we could show that recessive mutations in ALX1 and ALX4 genes underlie clinically distinct forms of frontonasal dysplasias (Uz E et al. Am J Hum Genet 2010, Kayserili H et al. Hum Mol Genet 2009), reported that Treacher Collins syndrome represents a ribosomopathy and is caused also by mutations in the POLR1C and POLR1D genes (Dauwerse JG et al. Nat Genet 2011), and identified regulatory alterations of SOX9, a novel disease-causing mechanism for craniofacial malformations, as cause for Pierre-Robin syndrome (Benko S et al. Nat Genet 2009). Moreover, molecular and functional studies provided further evidence that centrosomal dysfunction is responsible for microcephaly and facial dysmorphisms associated with Seckel syndrome (Kalay E et al. Nat Genet 2011), and showed that loss of CHSY1 function leads to alterations in BMP signallng causing craniosynostosis and hearing loss in patients with Temtamy preaxial brachydactyly syndrome (Li Y et al. Am J Hum Genet 2010).


Learning packages

This resource is part of the following learning package:

Similar resources


IMS Metadata


B. Wollnik. Craniofacial Malformations 2011. EUROGENE portal. September 2011. online:


Terms of use

This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License. Read more.