Treacher Collins Syndrome

Wang

et al. 2019

Orphanet J Rare Dis

Background Treacher Collins syndrome (TCS, OMIM 154500) is an autosomal disorder of craniofacial development with an incidence rate of 1/50,000 live births. Although TCOF1 , POLR1D , and POLR1C , have been identified as the pathogenic genes for about 90% TCS patients, the pathogenic variants of about 8–11% cases remain unknown. The object of this study is to describe the molecular basis of 14 clinically diagnosed TCS patients from four families using Whole-exome sequencing (WES) followed by Sanger sequencing confirmation, and to analyze the effect of bone conduction hearing rehabilitation in TCS patients with bilateral conductive hearing loss. Results Four previously unreported heterozygous pathogenic variants (c.3047-2A > G, c.2478 + 5G > A, c.489delC, c.648delC) were identified in the TCOF1 gene, one in each of the four families. Sanger sequencing in family members confirmed co-segregation of the identified TCOF1 variants with the phenotype. The mean pure-tone threshold improvements measured 3 months after hearing intervention were 28.8 dB for soft-band BAHA, 36.6 ± 2.0 dB for Ponto implantation, and 27.5 dB SPL for Bonebridge implantation. The mean speech discrimination improvements measured 3 months after hearing intervention in a sound field with a presentation level of 65 dB SPL were 44%, 51.25 ± 5.06, and 58%, respectively. All six patients undergoing hearing rehabilitation in this study got a satisfied hearing improvement. Conclusions WES combined with Sanger sequencing enables the molecular diagnosis of TCS and may detect other unknown causative genes. Bone conduction hearing rehabilitation may be an optimal option for TCS patients with bilateral conductive hearing loss.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TCOF1 pathogenic variants identified by Whole-exome sequencing in Chinese Treacher Collins syndrome families and hearing rehabilitation effect

Wang

et al. 2019

Orphanet J Rare Dis

“…TCS is currently managed by treating the clinical manifestations in relation to the patient’s specific needs. A multidisciplinary craniofacial management team handles the different symptoms with reconstructive surgery and speech therapy [ 81 ] ( Table 1 ).…”

Section: Ribosomopathies With Specific Correctionsmentioning

confidence: 99%

Ribosomopathies: New Therapeutic Perspectives

Orgebin

Lamoureux

Isidor

et al. 2020

Cells

Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

Journal of Craniofacial Surgery

“…Based on our own treatment experience and referring to the treatment of other researchers, [10][11][12][13][14] we have summarized the comprehensive serial treatment of TCS, which is mainly formulated based on patient age and deformity assessment for clinical reference (Supplemental Table 1, Supplemental Digital Content 4, http://links.lww.com/SCS/E179).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Serial Treatment of Treacher Collins Syndrome

Lei¹,

Huang²,

Sun³

et al. 2022

Objective: To discuss and summarize the comprehensive serial surgical treatment of Treacher Collins syndrome. Materials and Methods: From September 2012 to January 2020, 12 patients with Treacher Collins syndrome were treated by autologous fat graft, mandibular distraction osteogenesis, orbitozygomatic reconstruction with calvarial external lamina, orthognathic surgery combined with postoperative orthodontics, transplantation of upper eyelid orbicularis myocutaneous flap, lateral canthal ligament reduction, and other methods. The authors evaluated the postoperative improvement, summarized experiences, and reviewed literatures about the comprehensive serial treatment of Treacher Collins syndrome. Results: All patients showed significant improvement in appearance and function, and no complications were found during the follow-up period of 5 months to 3 years. Conclusions: The deformities of Treacher Collins syndrome involves multiple craniofacial region, and only by formulating comprehensive serial treatment strategies according to the malformation characteristics of different patients can the best effect be achieved.