A novel oculo-oto-facial dysplasia in a Native Alaskan community with autosomal recessive inheritance

Abstract

We describe a novel autosomal recessive malformation syndrome in four related individuals from a geographically isolated Native Alaskan community, who have facial defects similar to those of individuals with Treacher Collins (TCS) and Miller syndrome. Distinctive findings include malar and mandibular hypoplasia, lower eyelid coloboma, choanal atresia, orofacial clefting, and external ear malformation with preauricular tags. Intellect is normal and profound mixed hearing loss has been observed in affected adults. Variable extracranial findings include atrioseptal defect, renal dysplasia, and imperforate anus, however, no limb defects have been observed. Cranial imaging studies demonstrate relative prominence of the zygoma, inferior orbital maxillary hypoplasia, and lateral orbital wall defects with an accessory superior bony projection off the zygoma lateral to the orbital rim. We propose that these individuals have inherited a novel autosomal recessive condition we have termed oculo-oto-facial dysplasia (OOFD) with unique radiographic findings.

Mandibulofacial dysostosis in a patient with a de novo 2;17 translocation that disrupts the HOXD gene cluster

“…There have also been several reports documenting other unique mandibulofacial dysostoses syndromes separate from TCS [Verloes and Lesenfants, 1997;Delb et al, 2001;Hedera et al, 2002;Hing et al, 2006]. We report on a child with a provisionally unique mandibulofacial dysostosis and an apparently balanced de novo translocation involving chromosomes 2q and 17q.…”

Eyelids, Eyelashes, and Eyebrows

“…The proposed etiology is a mutation in the TCOF1 gene transmitted via autosomal dominant inheritance, but several instances of probable spontaneous mutations are seen in the literature (Hing et al 2006;Neligan 2012;Hoyt and Taylor 2013). There are several malformations seen with the eyelids including coloboma of the lower lids, antimongoloid obliquity of the palpebral fissures, dystopia of the lateral canthi, shortening of the palpebral fissure, absence of the eyelashes, and notching of eyebrows (Neligan 2012).…”

“…This is a very rare autosomal recessive disorder seen in a geographically isolated Native Alaskan community (Hing et al 2006). Cranial manifestations include lower eyelid coloboma, malar and mandibular hypoplasia, orofacial clefting, choanal atresia, and external ear malformation with preauricular tags.…”

“…Cranial manifestations include lower eyelid coloboma, malar and mandibular hypoplasia, orofacial clefting, choanal atresia, and external ear malformation with preauricular tags. Extra-cranial findings include atrioseptal defect, renal dysplasia, and imperforate anus (Hing et al 2006).…”

“…Lower lid colobomas are also associated with two distinct acrofacial defects (mandibulofacial dysostosis and limb defects): Nager syndrome (preaxial acrofacial dysostosis) and Miller syndrome (postaxial acrofacial dysostosis) (Hing et al 2006).…”