Additional findings of tibial dysplasia in a male with orofaciodigital syndrome type XVI

Abstract

We describe the case of a male patient with orofaciodigital (OFD) syndrome type XVI with a homozygous variant of TMEM107 (p.Phe106del) and the additional findings of tibial dysplasia, which is a pivotal finding of OFD syndrome type IV. His family history included two fetuses with anencephaly with or without cleft lip/palate and polydactyly with no genetic information. Careful attention should be given to the interpretation of this rare pattern.

Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid

“…Interestingly, similar phenotypes have been observed in humans. Patients who appear as homozygotes or compound heterozygotes for TMEM107 mutant allele have been diagnosed with Joubert (JS), Meckel–Gruber (MKS) or orofaciodigital syndrome (OFD) ( Iglesias et al, 2014 ; Shaheen et al, 2015 ; Lambacher et al, 2016 ; Shylo et al, 2016 ; Chinen et al, 2022 ). All abovementioned syndromes have been recognized as ciliopathies associated with eye defects like anophthalmia , microphthalmia , retinal defects, coloboma or lid anomalies ( Hartill et al, 2017 ; Hartill et al, 2017 ).…”

“…All abovementioned syndromes have been recognized as ciliopathies associated with eye defects like anophthalmia , microphthalmia , retinal defects, coloboma or lid anomalies ( Hartill et al, 2017 ; Hartill et al, 2017 ). Patients with TMEM107 pathological variants were diagnosed with a stronger phenotype in case of MKS with bilateral anophthalmia ( Shaheen et al, 2015 ), and milder phenotypes with OFD and JBT with oculomotor apraxia and retinopathy ( Lambacher et al, 2016 ), and OFD with strabismus ( Chinen et al, 2022 ). Severity of exhibited symptoms seems to be correlated with the type of patients´ mutations.…”

“…TMEM107 is a protein located at the TZ that has been shown to recruit ciliopathy-associated proteins such as MKS-1, TMEM-231 (JBTS20), and JBTS-14 (TMEM237) to this domain ( Lambacher et al, 2016 ). The TMEM107 locus has recently been found to be mutated in patients with Meckel–Gruber syndrome, Orofaciodigital syndrome, and Joubert syndrome ( Iglesias et al, 2014 ; Shaheen et al, 2015 ; Lambacher et al, 2016 ; Shylo et al, 2016 ; Chinen et al, 2022 ). These syndromes are associated with altered primary cilia morphology and function, highlighting the role of TMEM107 in ciliary function.…”

“…Human patients with TMEM107 mutations exhibit numerous developmental defects, such as polydactyly or facial dysmorphic features ( Iglesias et al, 2014 ; Lambacher et al, 2016 ; Shylo et al, 2016 ; Chinen et al, 2022 ). Mouse strains with mutations in Tmem107 demonstrate similar defects to human patients, including extra digits and a spectrum of craniofacial anomalies such as exencephaly, microphthalmia or skeletal defects in Tmem107 schlei embryos ( Christopher et al, 2012 ).…”