Human facial dysostoses

Abstract

The human facial dysostoses can be subdivided into mandibulofacial dysostoses (MFDs) and acrofacial dysostoses (AFDs). The craniofacial phenotypes of the two groups of patients are similar. Both types are thought to be related to abnormal migration of neural crest cells to the pharyngeal arches and the face. The craniofacial anomalies shared by the two groups consist of downslanting palpebral fissures, coloboma of the lower eyelid, from which the eyelashes medial to the defect may be absent, hypoplasia of the zygomatic complex, micrognathia, and microtia, which is often associated with hearing loss. These facial deformities are associated with limb anomalies in the AFDs. All MFDs present with the typical craniofacial phenotype, but some have additional features that help to distinguish them clinically: intellectual disability, microcephaly, chest deformity, ptosis, cleft lip/palate, macroblepharon, or blepharophimosis. The limb anomalies in the AFDs can be classified into pre-axial, post-axial, and others not fitting into the first two AFD types. Of the pre-axial types, Nager syndrome and of the post-axial types, Miller syndrome are the best-known disorders of their AFD subgroups. Several other AFDs with unknown molecular genetic bases, including lethal ones, have been described. This article reviews the MFDs and AFDs published to date.

The characteristics of craniofacial and cervicovertebral morphology in different genetic syndromes: A literature review and three case reports

“…In addition, some patients may exhibit congenital heart defects. [71][72][73] Hemifacial microsomia primarily affects the development of the ear, mouth and mandible, while Goldenhar syndrome shows vertebral abnormalities, epibulbar dermoids and facial deformities. 74 Management of craniofacial syndromes is aimed at the specific needs of each individual.…”

The hutterite variant of treacher collins syndrome: A 28‐year‐old story solved

“…There is a well-established phenotype, and the lack of limb anomalies primarily differentiates TCS and MFD from other similar disorders such as the acrofacial dysostoses. A recent review of MFD identified eight separate clinical entities including Hutterite Type MFD [Wieczorek, 2013]. Only one of them, TCS, has been extensively studied and molecularly characterized with two further clinical subtypes of unclear underlying mechanism [Wieczorek, 2013].…”

“…A recent review of MFD identified eight separate clinical entities including Hutterite Type MFD [Wieczorek, 2013]. Only one of them, TCS, has been extensively studied and molecularly characterized with two further clinical subtypes of unclear underlying mechanism [Wieczorek, 2013]. The main gene involved in the cause of TCS, TCOF1 (OMIM# 606847), was discovered in 1996 [Treacher Collins Syndrome Collaborative Group, 1996], and about 60% of TCS patients have de novo autosomal dominant (AD) mutations [Teber et al, 2004].…”

The Contributions of the Ribosome Biogenesis Protein Utp5/WDR43 to Craniofacial Development

“…Furthermore, another RNAPI subunit, POLR1A, is mutated in patients with a craniofacial disorder called acrofacial dysostosis, Cincinnati type (Weaver et al 2015). Unlike Treacher Collins syndrome, acrofacial dysostoses are characterized by developmental defects of the limbs and craniofacial structures (Wieczorek 2013). Thus, mutations in multiple proteins physically involved in the transcription or pre-rRNA or in the initiation of pre-rRNA transcription cause a human disease associated with defects in craniofacial development.…”