scholarly journals Biallelic CDK9 variants as a cause of a new multiple-malformation syndrome with retinal dystrophy mimicking the CHARGE syndrome

2021 ◽  
Author(s):  
Sachiko Nishina ◽  
Katsuhiro Hosono ◽  
Shizuka Ishitani ◽  
Kenjiro Kosaki ◽  
Tadashi Yokoi ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Retinal Dystrophy ◽  
Facial Asymmetry ◽  
Charge Syndrome ◽  
Compound Heterozygous ◽  
Malformation Syndrome ◽  
Duane Syndrome ◽  
Compound Heterozygous Variants ◽  
A Charge

AbstractCDK9 has been considered a candidate gene involved in the CHARGE-like syndrome in a pair of cousins. We report an 8-year-old boy with a strikingly similar phenotype including facial asymmetry, microtia with preauricular tags and bilateral hearing loss, cleft lip and palate, cardiac dysrhythmia, and undescended testes. Joint contracture, no finger flexion creases, and large halluces were the same as those of a previously reported patient with homozygous CDK9 variants. The ocular phenotype included blepharophimosis, lacrimal duct obstruction, eyelid dermoids, Duane syndrome-like abduction deficit, and congenital cataracts. Optical coherence tomography and electroretinography evaluations revealed severe retinal dystrophy had developed at an early age. Trio-based whole-exome sequencing identified compound heterozygous variants in CDK9 [p.(A288T) of maternal origin and p.(R303C) of paternal origin] in the patient. Variants’ kinase activities were reduced compared with wild type. We concluded that CDK9 biallelic variants cause a CHARGE-like malformation syndrome with retinal dystrophy as a distinguishing feature.

scholarly journals COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sami Tabbarah ◽  
Erika Tavares ◽  
Jason Charish ◽  
Ajoy Vincent ◽  
Andrew Paterson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Retinal Degeneration ◽  
Skeletal Dysplasia ◽  
Early Onset ◽  
Protein Misfolding ◽  
Cultured Cells ◽  
Retinal Dystrophy ◽  
Compound Heterozygous ◽  
Cog Complex ◽  
Compound Heterozygous Variants

AbstractLeber congenital amaurosis (LCA), a form of autosomal recessive severe early-onset retinal degeneration, is an important cause of childhood blindness. This may be associated with systemic features or not. Here we identified COG5 compound-heterozygous variants in patients affected with a complex LCA phenotype associated with microcephaly and skeletal dysplasia. COG5 is a component of the COG complex, which facilitates retrograde Golgi trafficking; if disrupted this can result in protein misfolding. To date, variants in COG5 have been associated with a distinct congenital disorder of glycosylation (type IIi) and with a variant of Friedreich’s ataxia. We show that COG5 variants can also result in fragmentation of the Golgi apparatus and upregulation of the UPR modulator, PKR-like endoplasmic reticulum kinase (PERK). In addition, upregulation of PERK induces DNA damage in cultured cells and in murine retina. This study identifies a novel role for COG5 in maintaining ER protein homeostasis and that disruption of that role results in activation of PERK and early-onset retinal degeneration, microcephaly and skeletal dysplasia. These results also highlight the importance of the UPR pathway in early-onset retinal dystrophy and as potential therapeutic targets for patients.

Mandibular Asymmetry and Antigonial Notching in Individuals with Unilateral Cleft Lip and Palate

2002 ◽  
Vol 39 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Stephanos Kyrkanides ◽  
Liubov Richter
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Facial Asymmetry ◽  
Skeletal Maturation ◽  
Growth Spurt ◽  
Pubertal Growth Spurt ◽  
Panoramic Radiographs ◽  
Pubertal Growth ◽  
Mandibular Asymmetry ◽  
Orthodontic Patients

Objective To determine whether asymmetric antigonial notching is associated with the development of mandibular and lower facial asymmetry in individuals with unilateral cleft lip and palate (UCLP). Design Retrospective mixed-longitudinal investigation including UCLP and nonaffected orthodontic patients. Participants All (24) available patients with UCLP treated in our clinic with complete longitudinal records, and 72 skeletal maturation matched noncleft orthodontic patients that served as controls. Subject records included hand-wrist, panoramic, frontal, and 45° oblique cephalometric radiographs. Main outcome Measures The development of mandibular asymmetry, measured on oblique cephalometric radiographs, as well as lower facial asymmetry, measured on frontal cephalometric radiographs, was monitored in individuals with UCLP in relation to antigonial notching asymmetry, assessed on panoramic and oblique cephalometric radiographs. Results First, no statistical differences were found in antigonial notching asymmetry between patients with UCLP and noncleft controls. Second, antigonial notching asymmetry, observed on panoramic and oblique cephalometric radiographs, significantly correlated with the attendant development of mandibular and lower facial asymmetry in individuals with UCLP. Third, the development of mandibular and lower facial asymmetry at pubertal and post-pubertal growth spurt stages significantly correlated with antigonial notching asymmetry, measured on panoramic radiographs, at prepubertal and pubertal growth spurt stages, respectively. Conclusions The degree of antigonial notching noted on panoramic radiographs can be used as an early indicator of developing mandibular and lower facial asymmetry in individuals with UCLP.

Three-Dimensional Evaluation of Facial Asymmetry in Cleft Lip and Palate

1994 ◽  
Vol 31 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Frank Ras ◽  
Luc L. M. H. Habets ◽  
Floris C. Van Ginkel ◽  
Birte Prahl-Andersen
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Three Dimensional ◽  
Facial Asymmetry

scholarly journals Coronal clival cleft in CHARGE syndrome

2017 ◽  
Vol 30 (6) ◽  
pp. 574-577 ◽  
Author(s):  
Eman Mahdi ◽  
Matthew T Whitehead
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Genetic Disorder ◽  
Ductus Arteriosus ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Craniocervical Junction ◽  
Undescended Testes ◽  
Ear Anomalies ◽  
Patent Ductus

CHARGE syndrome is a genetic disorder with multi-systemic congenital anomalies, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome has been refined over the years. However, there are limited reports describing skullbase and craniocervical junction abnormalities. These osseous malformations are often under recognized, especially on MRI. We report here a case of CHARGE syndrome with colobomas, cleft lip and palate, patent ductus arteriosus, undescended testes, and a coronal clival cleft which has not been previously depicted in CHARGE syndrome. The presence of a coronal clival cleft should alert the radiologist to examine the ears, eyes, palate, choana, and olfactory centers for other signs of CHARGE syndrome.

scholarly journals Secondary alveolar bone graft in patients with bilateral cleft lip and palate submitted to premaxilla repositioning: retrospective study

RSBO ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. 05-10
Author(s):  
Tuanny Carvalho de Lima do Nascimento ◽  
Fernando Luiz Zanferrari ◽  
Juliana Lucena Schussel ◽  
José Luís Dissenha ◽  
Laurindo Moacir Sassi ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Bone Graft ◽  
Medical Records ◽  
Cleft Lip ◽  
Statistical Data ◽  
Cleft Lip And Palate ◽  
Alveolar Bone ◽  
Care Center ◽  
Facial Asymmetry ◽  
Bilateral Cleft Lip

This study aimed to analyze the effectiveness of the closure of oronasal communication, to report the importance of secondary alveolar bone graft repositioning of the premaxilla in patients with bilateral complete cleft lip and palate. Material and methods: This retrospective study analyzed the medical records obtained from the Cleft Lip and Palate Integral Care Center/ Association of Rehabilitation and Social Development of Cleft Lip and Palate Patients (CAIF/AFISSUR), Curitiba – Paraná – Brazil, to obtain statistical data involving 26 records of patients who underwent this surgery in the period between January/2010 – January/2014. Results and Conclusion: The benefits observed were: premaxilla stability, aided by the union of pre-maxillary segments; integrity of oronasal structure; aesthetic improvement; better bone support for the teeth adjacent to the cleft; support for the bridge of the nose reducing facial asymmetry and facilitating future rhinoplasty; orthodontic treatment without the limitation of the bone defect; closure of oronasal communication in 88% of patients.

Cleft Skeletal Asymmetry

2017 ◽  
Vol 55 (3) ◽  
pp. 348-355 ◽  
Author(s):  
Delnaz S. Patel ◽  
Rachel Jacobson ◽  
Yao Duan ◽  
Linping Zhao ◽  
David Morris ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Quantitative Measure ◽  
Facial Asymmetry ◽  
Asymmetry Index ◽  
Control Group ◽  
Facial Skeleton ◽  
Midsagittal Plane ◽  
The Asymmetry ◽  
Skeletal Asymmetry

Objective: To quantitatively measure the extent of 3D asymmetry of the facial skeleton in patients with unilateral cleft lip and palate (UCLP) using an asymmetry index (AI) approach, and to illustrate the applicability of the index in guiding and measuring treatment outcome. Method: Two groups of subjects between the ages of 15 and 20 who had archived CBCT scan were included in this study. Twenty-five patients with complete UCLP were compared with 50 age-matched noncleft subjects. The CBCT scans were segmented and landmarked for 3D anthropometric analysis. An AI was calculated as a quantitative measure of the extent of facial skeletal asymmetry. Results: For the control group, the AI ranged from 0.72 ± 0.47 at A point to 4.77 ± 1.59 at Gonion. The degree of asymmetry increased with the increasing laterality of the landmark from the midsagittal plane. In the UCLP group, the values of AI significantly increased compared to the control group at nearly all measured landmarks. The extent of the asymmetry to involve the upper, middle, and lower facial skeleton varied widely with the individual patient with UCLP. Conclusion: The asymmetry index is capable of capturing the 3D facial asymmetry of subjects with UCLP and as a basis for classification of the extent of the asymmetry. We found the index to be applicable in surgical planning and in measuring the outcome in improving the symmetry in patients who have undergone orthognathic surgery.

Three-Dimensional Evaluation of Facial Asymmetry in Cleft Lip and Palate

1994 ◽  
Vol 31 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Frank Ras ◽  
Luc L.M.H. Habets ◽  
Floris C. Van Ginkel ◽  
Birte Prahl-Andersen
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Three Dimensional ◽  
Vertical Direction ◽  
Facial Asymmetry ◽  
Three Dimensions ◽  
Control Group ◽  
Craniofacial Anomalies ◽  
Facial Landmarks ◽  
Three Components

The purpose of the present study was to describe facial asymmetry in three dimensions in individuals with an operated complete unilateral cleft lip and palate (UCLP) and in individuals without craniofacial anomalies (controls). Three-dimensional coordinates for 16 bilateral and 10 midsagittal facial landmarks were determined for the UCLP group (N=49) and the control group (N=80) by means of stereophotogrammetry. The total asymmetry was measured and resolved for transverse, vertical, and sagittal components. It can be concluded that all three components are Important in studies on facial asymmetry. Individuals with UCLP show more facial asymmetry in the vertical direction than controls. They demonstrate more facial asymmetry in the region related to the cleft than controls. And, males in general demonstrate more asymmetry of the nose than females.

scholarly journals Longitudinal 3D Assessment of Facial Asymmetry in Unilateral Cleft Lip and Palate

2018 ◽  
Vol 56 (4) ◽  
pp. 495-501 ◽  
Author(s):  
Dhelal Al-Rudainy ◽  
Xiangyang Ju ◽  
Felicity V. Mehendale ◽  
Ashraf Ayoub
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Facial Asymmetry

Mandibular Asymmetry in Noncleft and Unilateral Cleft Lip and Palate Individuals

1997 ◽  
Vol 34 (5) ◽  
pp. 410-416 ◽  
Author(s):  
Christodoulos P. Laspos ◽  
Stephanos Kyrkanides ◽  
Ross H. Tallents ◽  
Mark E. Moss ◽  
J. Daniel Subtelny
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Age Groups ◽  
Facial Asymmetry ◽  
Cranial Base ◽  
Temporal Region ◽  
Facial Skeleton ◽  
Mandibular Asymmetry ◽  
The Asymmetry

Objective: The purpose of this study was to retrospectively investigate mandibular asymmetry in unilateral cleft lip and palate individuals (UCLP) in relation to chronologic age and in relation to lower facial asymmetry. Design: The longitudinal records of 34 UCLP individuals and 142 controls treated in the Department of Orthodontics, Eastman Dental Center, Rochester, NY, were included in the study. Posteroanterior and oblique cephalometric radiographs were analyzed for lower facial asymmetry and mandibular asymmetry, respectively. Mandibular asymmetry in UCLP was analyzed relative to three age groups (6–10, 11–14, and 15 or greater) and compared to controls. Moreover, mandibular asymmetry was analyzed relative to lower facial asymmetry. Results: UCLP individuals showed no significant differences in mandibular asymmetry compared to controls. In addition, no significant correlation was found between mandibular asymmetry and lower facial asymmetry in UCLP. Conclusions: The degree of mandibular asymmetry in UCLP appears not to be the major contributing factor to the lower facial asymmetry noted on these individuals. Possible cranial-base/temporal-region anomalies may be involved in unilateral cleft lip and palate and be responsible of the asymmetry noted in the lower facial skeleton.

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