Molecular Genetics of Human Facial Dysostoses

Abstract

Human facial dysostoses comprise mandibulofacial (MFDs) and acrofacial dysostoses (AFDs). Both types are characterised by similar craniofacial dysmorphisms, which are assumed to be caused by an abnormal development of the neural crest cells. Craniofacial anomalies consist of downslanting palpebral fissures, lower eyelid coloboma with or without absence of lower eyelashes medial to the defect, hypoplasia of the zygomatic complex, micrognathia and microtia often associated with hearing loss. The facial anomalies are associated with limb anomalies in the AFDs, which are preaxial, postaxial or cannot be classified into one of these groups. The molecular basis for most of the MFDs and AFDs is unknown. For Treacher Collins syndrome ( TCOF1, POLR1D and POLR1C ) and MFD type Hutterite ( TCOF1 ), the molecular basis is known which is also true for three of the AFDs, Nager syndrome ( SF3B4 ), Miller syndrome ( DHODH ) and AFD type Guion‐Almeida ( EFTUD2 ). Key Concepts: In human facial dysostoses, the development of the structures of the first and second branchial arches is disturbed. Facial dysostoses can be subdivided into those with normal extremities, the mandibulofacial dysostoses (MFDs), and those with anomalies of limbs, the acrofacial dysostoses. TCOF1 mutations are causal for Treacher Collins syndrome and MFD type Hutterite. POLR1D and POLR1C mutations are causal for Treacher Collins syndrome. SF3B4 mutations are causal for Nager syndrome. EFTUD2 mutations are causal for ADGA. DHODH mutations are causal for Miller syndrome. EVC and EVC2 mutations are causal for Weyers syndrome.