Oculo–facio–cardio–dental syndrome with craniosynostosis, temporal hypertrichosis, and deafness

Abstract

We report the case of a 7-month-old girl with atypical oculo-facio-cardio-dental syndrome (OFCD). A novel de novo pathogenic mutation in the BCL6 interacting co-repressor gene (BCOR) (c.4540C>T; p.Arg1514*), was identified on the X chromosome. This case expands the phenotype of OFCD as it is the first report of a case presenting with craniosynostois, temporal hypertrichosis, supraorbital grooving, and underdevelopment of the midface.

A Higher Proportion of Craniosynostosis Genes Are Cancer Driver Genes

“…These 17 new genes found through this process were added to the CRS genes list: AXIN2 (Yilmaz et al, 2018), BBS9 (Justice et al, 2012; Sewda et al, 2019), BCOR (O’Byrne et al, 2017) (for Oculo-facio-cardio-dental syndrome, or microphthalmia syndrome), BGLAP (Sowińska-Seidler et al, 2018), COLEC10 (for 3MC syndrome) (Munye et al, 2017), FGFRL1 (Rieckmann et al, 2009) (for Antley-Bixler syndrome), GCK (for Greig cephalopolysyndactyly syndrome) (Zung et al, 2011), LMNA (Sowińska-Seidler et al, 2018), PPP3CA (Mizuguchi et al, 2018), PTH2R (Kim et al, 2015), RAF1 (for Noonan syndrome with multiple lentigines, or leopard syndrome) (Rodríguez et al, 2019), SIX2 (for frontonasal dysplasia syndrome) (Hufnagel et al, 2016), SMURF1, SPRY1, SPRY4 (Timberlake et al, 2016, 2017), TCOF1 (for Treacher Collins syndrome) (Horiuchi et al, 2004), TNFRSF11B (for Juvenile Paget disease) (Saki et al, 2013).…”

Microphthalmia is not a mandatory finding in X‐linked recessive syndromic microphthalmia caused by the recurrent BCOR variant p.Pro85Leu

“…Note . OFCD, N = 66: Danda et al, ; Di Stefano et al, ; Feberwee et al, ; Hilton et al, ; Horn et al, ; Kondo et al, ; Lozic et al, ; Ma et al, ; Ng et al, ; O'Byrne et al, ; Surapornsawasd et al, ; Zhou et al, .…”

“…BCOR belongs to the growing number of X‐chromosomal genes in which mutations cause allelic, overlapping but still distinct phenotypes in females and males. More than 65 females with OFCD carrying a heterozygous null allele of BCOR have been reported in literature up to date (Danda et al, ; Di Stefano et al, ; Feberwee et al, ; Hilton et al, ; Horn et al, ; Kondo et al, ; Ma et al, ; Ng et al, ; O'Byrne et al, ; Surapornsawasd et al, ; Zhou et al, ). In contrast, only four males and one aborted fetus from three families with Lenz microphthalmia have been reported.…”

“…This phenotype includes variable microphthalmia, congenital cataracts, facial dysmorphism along with cardiac, dental, and skeletal anomalies. Intelligence is normal in the majority of affected individuals (Danda et al, ; Di Stefano et al, ; Feberwee et al, ; Hilton et al, ; Horn et al, ; Kondo et al, ; Lozic et al, ; Ma et al, ; Ng et al, ; O'Byrne, Laffan, Murray, & Reardon, ; Surapornsawasd, Ogawa, Tsuji, & Moriyama, ; Zhou, Wojcik, Sanders, Rahmani, & Kurup, ). Truncating mutations in females occur either de novo or are inherited in an X‐linked dominant pattern.…”

Principales entidades genéticas asociadas con dientes supernumerarios

“…E l s í n d r o m e o c u l o f a c i o c a r d i o d e n t a l (OMIM 300166) es un trastorno dominante raro, ligado al cromosoma X, observado en las mujeres heterocigotas y que es letal en los varones. 52,53 Es causado por mutaciones heterocigotas en el gen BCOR (OMIM 300485), que codifica una proteína conocida como correpresor BCL6 y se encuentra en el cromosoma Xp11.4. 52,54,55 Este gen se expresa predominantemente durante la embriogénesis temprana, y la proteína codificada BCOR funciona como correpresor transcripcional.…”