Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: A mandibulofacial dysostosis distinct from Treacher Collins syndrome

Abstract

Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined mandibulofacial dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other mandibulofacial dysostoses (MDs) such as Toriello (OMIM 301950), Bauru (OMIM 604830), Hedera-Toriello-Petty (OMIM 608257), and Guion-Almeida (OMIM 610536) syndromes are less well characterized and much rarer. Here we describe three unrelated patients showing clinical features overlapping with TCS, but who in addition have developmental delay, microcephaly and a distinct facial gestalt. Because of the distinct ear anomalies and the hearing loss a HOXA2 mutation was taken into account. CHARGE syndrome was discussed because of ear anomalies, choanal atresia, and developmental delay in our patients. But mutational analyses including sequencing of the TCOF1, the HOXA2, and the CHD7 genes, deletion screening of the TCOF1 gene as well as genomewide array analyses revealed normal results. We suggest that these three patients have a new type of mandibulofacial dysostosis. As all three cases are sporadic and both sexes are affected the pattern of inheritance might be autosomal dominant or autosomal recessive. Identification of additional patients will allow to further delineate the phenotype, to assign the inheritance pattern and to identify the molecular basis.

Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations

“…This condition was characterized by microcephaly, a characteristic craniofacial appearance with upslanting palpebral fissures, microtia, preauricular and buccal tags and intellectual disability [3,4]. In the paper by Lines et al [2] only five of twelve patients had anomalies of the thumbs.…”

Heterogenność kliniczna i genetyczna dyzostoz twarzowych

“…W 2009 roku Wieczorek i wsp. opisali pacjentów z podobnym fenotypem i małogłowiem oraz dodatkowo z zarośnięciem nozdrzy tylnych [21]. Początkowo myślano, że jest to nowy typ dyzostoz i w bazach dysmorfologicznych określano go jako MFD typ Wieczorek.…”

Phenotype analysis of Polish patients with mandibulofacial dysostosis type Guion-Almeida associated with esophageal atresia and choanal atresia caused by EFTUD2 gene mutations

“…CHARGE, Treacher Collins and Noonan syndromes were considered as differential diagnosis during his first evaluation at a Genetic Counseling Unit at the age of 12. (Wieczorek et al 2009). In 2012, Lines et al identified heterozygous mutations in the EFTUD2 gene located at 17q21 as well as microdeletions involving the chromosomal region 17q21 in patients with mandibulofacial dysostosis with microcephaly (Lines et al 2012).…”

“…More reports described MFD associated with a major defect such as choanal atresia and esophageal atresia, kidney and heart defects and thumb hypoplasia (Wieczorek et al 2009;Guion-Almeida et al 2009;Gordon et al 2012;Luquetti et al 2013;Voigt et al 2013). Different names of this new entity were used in literature -mandibulofacial dysostosis type Wieczorek or oto-facial syndrome with midline malformation (Wieczorek 2013).…”