ABSTRACT
To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB). This was a retrospective study including 75 patients: 33 treated by LFIII, 29 by MB, and 13 by FB. Twenty-five had a diagnosis of Apert, 39 Crouzon, and 11 craniofrontonasal syndrome. A three-dimensional mesh was created from the preoperative scan and registered to the postoperative scan to visualise the advancement. LFIII at age 7-12 years effectuated a higher mean advancement in the maxillary (15.5 mm) and zygomatic (7.6 mm) regions when compared to ≥13 years (10.2 mm and 5.5 mm). After MB, mean advancement of the fronto-orbital region was higher at <7 years (16.4 mm), and similarly lower at ages 7-12 (13.8 mm) and ≥13 (12.5 mm). The mean preoperative inter-dacryon distance (34.4 ± 4.4 mm) was reduced by 8.7 ± 4.2 mm after FB without distraction (n = 10). More advancement was seen when midface surgery was performed at a younger age, due to more severe cases and a desire for overcorrection. The highest mean advancement was observed in the fronto-orbital region. Antero-inferior rotational movement was seen after all three techniques.
Subject(s)
Imaging, Three-Dimensional , Osteotomy, Le Fort , Humans , Child , Retrospective Studies , Female , Male , Osteotomy, Le Fort/methods , Imaging, Three-Dimensional/methods , Adolescent , Treatment Outcome , Craniofacial Abnormalities/surgery , Craniofacial Abnormalities/diagnostic imaging , Facial Bones/surgery , Facial Bones/diagnostic imaging , Facial Bones/abnormalities , Craniosynostoses/surgery , Craniosynostoses/diagnostic imaging , Tomography, X-Ray Computed/methods , Craniofacial Dysostosis/surgery , Craniofacial Dysostosis/diagnostic imaging , Osteogenesis, Distraction/methods , Cephalometry , Surgical MeshABSTRACT
The aim of the research was to study the relationship between the X-ray changes in the bones of the skull, the structure of the upper respiratory tract and concomitant general somatic diseases in patients with congenital and acquired craniomaxillofacial anomalies. The study included 52 patients aged 1 to 3 and 3 to 7 years, with congenital and acquired lower micrognathia in 19 (36.53±5.3)% and upper micrognathia in 33 (63.46±5.3)%. There were used clinical methods (questioning, examination, palpation), instrumental methods (multispiral computer tomography, X-ray cephalometric analysis of the bones of the facial skeleton, oropharynx, and bony pharynx). The obtained results of the clinical and radiographic examination made it possible to assert that among the patients with congenital defects of the jaws, not only changes in the facial skeleton dominate, mostly in the form of upper micrognathia and, to a lesser extent, lower micrognathia, but also the presence of somatic developmental defects in the form of disorders of the nervous system, pathologies of ENT-organs and ophthalmic defects. The identified malformations caused the violations of a number of important functions: breathing, swallowing, chewing, and speech formation. This connection was followed in particular in patients with syndromic craniosynostosis, namely, underdevelopment of the skull base combined with upper micrognathia and retroposition of the maxillary complex in the skull. The frequency and spectrum of concomitant somatic pathology depended on the nature of dentofacial anomalies. All patients with upper micrognathia had craniostenosis with the deformations of the brain skull and eye sockets. Among the patients with lower micrognathia, all those examined were found to have disorders of the development of the ENT-organs.
Subject(s)
Micrognathism , Humans , Skull/diagnostic imaging , Face , Maxilla , Cephalometry , Facial Bones/diagnostic imaging , Facial Bones/abnormalitiesABSTRACT
Los trastornos del desarrollo son aquellos padecimientos que se manifiestan por defectos en la embriogénesis de la región afectada. La cara del ser humano comienza su formación alrededor de la cuarta semana de vida intrauterina y se manifiesta gracias a la fusión de cinco prominencias: dos pares conocidas como maxilar y mandibular, y una impar conocida como frontonasal. Cuando esta fusión no se lleva a cabo de una forma óptima, aparecen numerosas alteraciones del desarrollo como el labio y paladar hendido, y la displasia frontonasal. La displasia frontonasal produce frecuentemente afecciones oculares, nasales y orales. Dentro de las manifestaciones orales destacan una forma atípica de hendidura labial o palatina, afecciones dentales y alteraciones en el crecimiento de la cara. Dada la gran relación que este padecimiento tiene con la cavidad oral resulta importante que el odontólogo conozca la etiología y las características clínicas de este trastorno (AU)
Developmental disorders are those conditions that are manifested by defects in the embryogenesis of the affected region. The human face begins its formation around the fourth week of intrauterine life and is manifested thanks to the fusion of five prominences: two pairs known as maxillary and mandibular and odd one known as frontonasal. When this fusion is not carried out in an optimal way, numerous developmental alterations appear, such as cleft lip and palate and frontonasal dysplasia. Frontonasal dysplasia frequently produces ocular, nasal and oral affections. Among the oral manifestations, and atypical form of clef lip and/or palate, dental affections and alterations in the growth of the face stand out. Given the great relationship that this condition has with the oral cavity, it is important for the dentist to know the etiology and clinical characteristics of this disorder (AU)
Subject(s)
Humans , Male , Female , Craniofacial Abnormalities/genetics , Craniofacial Dysostosis , Facial Bones/abnormalities , Nasal Bone/abnormalities , Oral Manifestations , Eye Abnormalities/genetics , Cleft Lip/etiology , Cleft Palate/etiologyABSTRACT
Infantile cranial development typically occurs in a predictable sequence of events; however, less is known about how the development occurs in isolated, nonsyndromic congenital craniofacial anomalies. Furthermore, the timing of pediatric cranioplasty has been extrapolated from adult studies. Thus, the management of nonsyndromic congenital craniofacial anomalies presents with unique challenges to the craniofacial surgeon. The authors describe the case of a baby girl who was born with right Tessier 3 cleft, cleft palate, anophthalmos, and severe left craniofacial microsomia with Pruzansky grade III left mandibular anomaly. By analyzing 3-dimensional chronological models of the patient, the authors found that her abnormal fontanelle initially increased in size until 22 weeks of age, with subsequent spontaneous closure at a rate of 60.53 mm2/y. Although similar cranial anomalies are typically surgically corrected early in life, delaying treatment until after 2 years of age may be appropriate in some patients, obviating surgical morbidity in the newborn period.
Subject(s)
Anophthalmos , Cleft Palate , Goldenhar Syndrome , Female , Humans , Infant , Cleft Palate/surgery , Facial Bones/abnormalities , SkullABSTRACT
Anatomic studies have identified that patients with Treacher Collins syndrome and some cases of bilateral craniofacial microsomia are characterized by multilevel airway obstruction as a result of hypoplasia and clockwise rotation of the maxillomandibular complex. Patients often remain tracheostomy-dependent despite multiple airway surgeries. Counterclockwise craniofacial distraction osteogenesis aims to correct the facial skeletal deformity and expand the upper airway volume by rotating the subcranial complex en bloc around the nasofrontal junction. Early results have demonstrated significant increases in the nasopharyngeal and oropharyngeal airway volumes with successful decannulation in a majority of patients who have undergone this operation.
Subject(s)
Goldenhar Syndrome/surgery , Mandibulofacial Dysostosis/surgery , Osteogenesis, Distraction/methods , Airway Obstruction/etiology , Airway Obstruction/surgery , Facial Bones/abnormalities , Facial Bones/surgery , Female , Humans , Male , Mandible/surgery , TracheostomyABSTRACT
Severe midface hypoplasia is often managed by Le Fort III distraction. Le Fort II distraction with zygomatic repositioning is a modification of the Le Fort III distraction operation aimed to correct abnormal facial ratios of patients with greater central than lateral midface deficiency. The operation starts with Le Fort III osteotomies and is followed by separation and fixation of bilateral zygomas. The central nasomaxillary Le Fort II segment is then distracted to achieve independent movements of the central and lateral midface. The Le Fort II zygomatic repositioning operation has become our procedure of choice for patients with Apert facial dysmorphology.
Subject(s)
Acrocephalosyndactylia/surgery , Osteotomy, Le Fort/methods , Zygoma/surgery , Facial Bones/abnormalities , Facial Bones/surgery , Female , Humans , Male , Maxilla/surgery , Osteogenesis, Distraction/methodsABSTRACT
The introduction of distraction osteogenesis to frontofacial monobloc advancement has increased the safety of the procedure. One hundred forty-seven patients with syndromic craniosynostosis underwent frontofacial monobloc advancement using 4 internal distractors. Twenty-five were aged 18 months or less. Ten patients presented with a tracheostomy, 5 (50%) were decannulated after surgery, and 3 others (30%) required an additional intervention before decannulation. Six patients required the addition of a transfacial pin and external traction. Very early frontofacial monobloc with 4 internal distractors is a safe and effective treatment to protect the ophthalmic, neurologic, and respiratory functions in infants with severe syndromic craniosynostosis.
Subject(s)
Craniofacial Dysostosis/surgery , Osteogenesis, Distraction/methods , Craniofacial Dysostosis/complications , Craniosynostoses/complications , Craniosynostoses/surgery , Facial Bones/abnormalities , Facial Bones/surgery , Female , Humans , Infant , Male , Occlusal Splints , Osteogenesis, Distraction/instrumentation , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/surgery , TracheostomyABSTRACT
Monobloc and bipartition advancement by external distraction plays a major role in the treatment of syndromic craniosynostosis. They can reverse the associated facial deformity and play a role in the management of ocular exposure, intracranial hypertension, and upper airway obstruction. Facial bipartition distraction corrects the intrinsic facial deformities of Apert syndrome. Both procedures are associated with relatively high complication rates principally related to ascending infection and persistent cerebrospinal fluid leaks. Modern perioperative management has resulted in a significant decline in complications. External distractors allow fine tuning of distraction vectors and improve outcome but are less well tolerated than internal distractors.
Subject(s)
Acrocephalosyndactylia/surgery , Craniofacial Dysostosis/surgery , Osteogenesis, Distraction/methods , Facial Bones/abnormalities , Facial Bones/surgery , Female , Humans , Male , Osteogenesis, Distraction/adverse effects , Osteogenesis, Distraction/instrumentationABSTRACT
Kenny-Caffey syndrome type 2 (KCS2) and osteocraniostenosis (OCS) are allelic disorders caused by heterozygous pathogenic variants in the FAM111A gene. Both conditions are characterized by gracile bones, characteristic facial features, hypomineralized skull with delayed closure of fontanelles and hypoparathyroidism. OCS and KCS2 are often referred to as FAM111A-related syndromes as a group; although OCS presents with a more severe, perinatal lethal phenotype. We report a novel FAM111A mutation in a fetus with poorly ossified skull, proportionate long extremities with thin diaphysis, and hypoplastic spleen consistent with FAM111A-related syndromes. Trio whole exome sequencing identified a p.Y562S de novo missense variant in the FAM111A gene. The variant shows significant similarity to other reported pathogenic mutations fitting proposed pathophysiologic mechanism which provide sufficient evidence for classification as likely pathogenic. Our report contributed a novel variant to the handful of OCS and KCS2 cases reported with pathogenic variants.
Subject(s)
Abnormalities, Multiple/genetics , Bone Diseases, Developmental/genetics , Craniofacial Abnormalities/genetics , Dwarfism/genetics , Hyperostosis, Cortical, Congenital/genetics , Hypocalcemia/genetics , Receptors, Virus/genetics , Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/pathology , Bone Diseases, Developmental/diagnosis , Bone Diseases, Developmental/diagnostic imaging , Bone Diseases, Developmental/pathology , Cardiovascular Abnormalities/diagnosis , Cardiovascular Abnormalities/genetics , Cardiovascular Abnormalities/pathology , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/diagnostic imaging , Craniofacial Abnormalities/pathology , Dwarfism/diagnosis , Dwarfism/diagnostic imaging , Dwarfism/pathology , Facial Bones/abnormalities , Facial Bones/pathology , Female , Fetus , Genetic Predisposition to Disease , Heterozygote , Humans , Hyperostosis, Cortical, Congenital/diagnosis , Hyperostosis, Cortical, Congenital/diagnostic imaging , Hyperostosis, Cortical, Congenital/pathology , Hypocalcemia/diagnosis , Hypocalcemia/diagnostic imaging , Hypocalcemia/pathology , Male , Mutation/genetics , Pregnancy , Skull/abnormalities , Skull/pathology , Spleen/abnormalities , Spleen/diagnostic imaging , Exome SequencingABSTRACT
BACKGROUND: Bone retains regenerative potential into adulthood, and surgeons harness this plasticity during distraction osteogenesis. The underlying biology governing bone development, repair, and regeneration is divergent between the craniofacial and appendicular skeleton. Each type of bone formation is characterized by unique molecular signaling and cellular behavior. Recent discoveries have elucidated the cellular and genetic processes underlying skeletal development and regeneration, providing an opportunity to couple biological and clinical knowledge to improve patient care. METHODS: A comprehensive literature review of basic and clinical literature regarding craniofacial and long bone development, regeneration, and distraction osteogenesis was performed. RESULTS: The current understanding in craniofacial and long bone development and regeneration is discussed, and clinical considerations for the respective distraction osteogenesis procedures are presented. CONCLUSIONS: Distraction osteogenesis is a powerful tool to regenerate bone and thus address a number of craniofacial and appendicular skeletal deficiencies. The molecular mechanisms underlying bone regeneration, however, remain elusive. Recent work has determined that embryologic morphogen gradients constitute important signals during regeneration. In addition, striking discoveries have illuminated the cellular processes underlying mandibular regeneration during distraction osteogenesis, showing that skeletal stem cells reactivate embryologic neural crest transcriptomic processes to carry out bone formation during regeneration. Furthermore, innovative adjuvant therapies to complement distraction osteogenesis use biological processes active in embryogenesis and regeneration. Additional research is needed to further characterize the underlying cellular mechanisms responsible for improved bone formation through adjuvant therapies and the role skeletal stem cells play during regeneration.
Subject(s)
Bone Diseases/surgery , Bone Regeneration , Osteogenesis, Distraction , Osteogenesis , Animals , Bone Diseases/physiopathology , Facial Bones/abnormalities , Facial Bones/physiology , Facial Bones/surgery , Humans , Models, Animal , Skeleton/physiology , Skeleton/surgery , Skull/physiology , Skull/surgeryABSTRACT
BACKGROUND Ethnic background may affect the prevalence of nasal bone absence and the length of the nasal bone. This study aimed to elucidate the significance of absent or hypoplastic fetal nasal bone in the Chinese Han population and to formulate an optimal management plan for patients age 35 or older in cases of isolated abnormal fetal nasal bone. MATERIAL AND METHODS We prospectively assigned pregnant women whose fetuses had nasal bone absence or hypoplasia to separate groups according to their choice for noninvasive prenatal screening (NIPS) between January 1, 2013, and December 31, 2018. Demographic data, ultrasound findings, results of conventional maternal serum screening and NIPS, fetal karyotype, pregnancy outcomes, and expenses associated with prenatal testing were recorded. The incidence and odds ratio of nasal bone abnormality and the sensitivity and specificity of different prenatal genetic screening tests were calculated. RESULTS A total of 1946 cases with fetal nasal bone absence or hypoplasia were included. Cases of isolated nasal bone abnormality (1736 cases) were divided into the NIPS group (Gr 1, n=429) and the non-NIPS group (Gr 2, n=1307). Sixty-four cases involved chromosomal abnormality. The sensitivity, specificity, and positive and negative predictive values of NIPS in Gr 1 were 100%, 100%, 100%, and 100%, respectively. The odds ratio of fetal chromosomal abnormalities for isolated fetal nasal bone abnormalities when maternal age was ≥35 was 4.615 (95% CI: 1.592-13.381). The cost-effectiveness ratio of contingent screening (NIPS first) was significantly lower than amniocentesis directly. CONCLUSIONS The nasal bone provides an important marker for chromosome abnormalities in some populations, but to a lesser extent in the Chinese Han population. NIPS is an excellent first option for follow-up among pregnant women age ≥35 in cases of absent or hypoplastic fetal nasal bone in the first trimester ultrasound scan.
Subject(s)
Facial Bones/abnormalities , Noninvasive Prenatal Testing/methods , Noninvasive Prenatal Testing/trends , Adult , Asian People/genetics , Biomarkers/blood , China , Chromosome Aberrations , Chromosome Disorders/diagnosis , Ethnicity/genetics , Facial Bones/diagnostic imaging , Female , Genetic Testing , Humans , Karyotyping , Maternal Age , Middle Aged , Nasal Bone/diagnostic imaging , Pregnancy , Pregnant Women , Prenatal Diagnosis/methods , Ultrasonography, Prenatal/methodsSubject(s)
Facial Asymmetry/congenital , Facial Asymmetry/diagnostic imaging , Facial Bones/abnormalities , Facial Bones/diagnostic imaging , Gingival Hyperplasia/congenital , Gingival Hyperplasia/diagnostic imaging , Facial Asymmetry/pathology , Facial Bones/pathology , Gingival Hyperplasia/pathology , Humans , Male , Tooth Abnormalities/diagnostic imaging , Tooth Abnormalities/etiology , Young AdultABSTRACT
This report summarizes findings relating to the biochemical and skeletal evidence for Treponema pallidum in an unusually old case of congenital syphilis. In 1951, the Milwaukee Public Museum acquired skeletal remains from the Surgical School of Marquette University. The male was identified as a 60-65-year-old, that was suffering from congenital syphilis. His remains are now part of the anthropological collections of Wisconsin Lutheran College (Milwaukee, Wisconsin). Venereal Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR) tests were used to verify the presence of the bacteria-generated antibodies, while mass spectrometry testing provided indirect evidence for the historical treatment of the disease. Notably, antibody detection in human remains of this age is rare. These initial results support what is known of syphilis and its treatment prior to the wide scale, clinical use of penicillin therapy, and describe evidence for long-term skeletal symptoms of congenital syphilis in century-old human remains.
Subject(s)
Bone and Bones/pathology , Cadaver , Syphilis, Congenital/pathology , Aged , Anodontia/pathology , Antibodies, Bacterial/analysis , Bone Resorption , Craniosynostoses/pathology , Edema/pathology , Facial Bones/abnormalities , History, 20th Century , Humans , Joints/pathology , Male , Malnutrition/pathology , Mass Spectrometry , Mercury/analysis , Middle Aged , Osteophyte/pathology , Treponema pallidumABSTRACT
Skeletal defects, such as cleft palate, scoliosis, and shortening of the limb bones are common in the human population. Animal models have been essential for characterizing the molecular and cellular mechanisms that underlie these and other skeletal disorders. This chapter will explore the cellular origins of the vertebrate skeleton and introduce a selection of animal models for human disorders of the skull and facial bones, spinal column, and limbs. The common genetic pathways that build the skeleton of various vertebrate species and how these similarities facilitate the study of human developmental processes in laboratory animals will be a focus of discussion. This chapter will also highlight how current genome editing technologies can be applied to model various perturbations of human chromatin structure in laboratory animals.
Subject(s)
Bone and Bones/abnormalities , Disease Models, Animal , Animals , Cleft Palate , Facial Bones/abnormalities , Humans , Skull/abnormalities , Spine/abnormalitiesABSTRACT
BACKGROUND: A recent artificial intelligence-based investigation has shown the impacts of orthognathic surgery on the patient's facial appearance and apparent age. However, appearance and age perception as reported by patients and surgical professionals have not been addressed in the same cohort to date. METHODS: FACE-Q facial appraisal (appearance and age) and quality-of-life scale scores obtained before and after orthognathic surgery, in addition to three-dimensional photographs of 70 patients with skeletal class III deformity, were collected for a comparative cross-sectional study. Seven blinded plastic surgeons rated all photographs for apparent facial aesthetic and age scales. The FACE-Q data from 57 matched normal individuals were adopted for the comparative analyses. The correlation between the FACE-Q and the professional-based scales was tested. RESULTS: Pre-orthognathic surgery versus post-orthognathic surgery comparisons showed significant differences (p < 0.001) for all FACE-Q scales and panel assessments, with higher (FACE-Q scales and professional-based aesthetic parameters) and lower (FACE-Q patient-perceived age scale and professional-based age parameter) values for post-orthognathic surgery measurements. Patients had significantly (p < 0.001) higher (patient-perceived age scale) and lower (facial appraisal and quality-of-life scales) FACE-Q values than normal individuals for pre-orthognathic surgery but not for post-orthognathic surgery measurements. The FACE-Q facial appearance overall scale had significant correlations (p < 0.001) with the panel assessment for the parameters "beautiful" and "attractive" but not for the "pleasant" parameter. No significant correlations were observed for facial age scales. CONCLUSION: This study contributes to the orthognathic surgery literature by revealing that orthognathic surgery positively impacts the perception of apparent facial age and improves facial appearance and quality of life. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Subject(s)
Aging/psychology , Face , Facial Bones/abnormalities , Orthognathic Surgical Procedures , Artificial Intelligence , Body Image/psychology , Esthetics , Facial Bones/surgery , Female , Humans , Imaging, Three-Dimensional , Male , Patient Satisfaction , Perception , Quality of LifeABSTRACT
Life in complete darkness has driven the evolution of a suite of troglobitic features in the blind Mexican cavefish Astyanax mexicanus, such as eye and pigmentation loss. While regressive evolution is a hallmark of obligate cave-dwelling organisms, constructive (or augmented) traits commonly arise as well. The cavefish cranium has undergone extensive changes compared with closely-related surface fish. These alterations are rooted in both cranial bones and surrounding sensory tissues such as enhancements in the gustatory and lateral line systems. Cavefish also harbor numerous cranial bone asymmetries: fluctuating asymmetry of individual bones and directional asymmetry in a dorsal bend of the skull. This asymmetry is mirrored by the asymmetrical patterning of mechanosensory neuromasts. We explored the relationship between facial bones and neuromasts using in vivo fluorescent colabeling and microcomputed tomography. We found an increase in neuromast density within dermal bone boundaries across three distinct populations of cavefish compared to surface-dwelling fish. We also show that eye loss disrupts early neuromast patterning, which in turn impacts the development of dermal bones. While cavefish exhibit alterations in cranial bone and neuromast patterning, each population varied in the severity. This variation may reflect observed differences in behavior across populations. For instance, a bend in the dorsal region of the skull may expose neuromasts to water flow on the opposite side of the face, enhancing sensory input and spatial mapping in the dark.
Subject(s)
Biological Evolution , Characidae/abnormalities , Craniofacial Abnormalities/veterinary , Animals , Anophthalmos/veterinary , Caves , Characidae/anatomy & histology , Darkness , Facial Bones/abnormalities , Imaging, Three-Dimensional , Quantitative Trait, Heritable , Skull/abnormalities , Skull/anatomy & histologyABSTRACT
OBJECTIVES: Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position. MATERIALS AND METHODS: Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution. RESULTS: Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31-3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0-1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2-55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative 'ideal' bone position was <1 cm in 82% of measurements. There were no flap losses. CONCLUSION: VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost.
Subject(s)
Computer Simulation , Facial Bones/surgery , Free Tissue Flaps , Plastic Surgery Procedures , Adult , Aged , Aged, 80 and over , Facial Bones/abnormalities , Facial Bones/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional/methods , Male , Middle Aged , Patient Care Planning , Plastic Surgery Procedures/methods , Young AdultSubject(s)
Chronic Kidney Disease-Mineral and Bone Disorder/diagnosis , Dialysis/adverse effects , Facial Bones/abnormalities , Kidney Failure, Chronic/complications , Adult , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Chronic Kidney Disease-Mineral and Bone Disorder/pathology , Dialysis/methods , Facial Bones/diagnostic imaging , Humans , Hyperparathyroidism, Secondary/complications , Hyperparathyroidism, Secondary/pathology , Hyperparathyroidism, Secondary/therapy , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/therapy , Kidney Transplantation/methods , Male , Malocclusion/diagnosis , Malocclusion/etiology , Parathyroidectomy/methods , Syndrome , Treatment Adherence and Compliance , Treatment OutcomeABSTRACT
A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic fissure fusion during vertebrate eye development. Our findings establish FAT1 as a gene with pleiotropic effects in human, in that frameshift mutations cause a severe multi-system disorder whereas recessive missense mutations had been previously associated with isolated glomerulotubular nephropathy.
Subject(s)
Blepharoptosis/genetics , Cadherins/genetics , Coloboma/genetics , Kidney Diseases/genetics , Microphthalmos/genetics , Organogenesis/genetics , Syndactyly/genetics , Adolescent , Adult , Animals , Cells, Cultured , Child , Child, Preschool , DNA Mutational Analysis , Embryo, Mammalian , Eye/embryology , Facial Bones/abnormalities , Female , Frameshift Mutation , Humans , Intercellular Junctions/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Primary Cell Culture , Retinal Pigment Epithelium/cytology , Syndrome , Exome Sequencing , Young Adult , Zebrafish , Zebrafish Proteins/geneticsABSTRACT
BACKGROUND: The prevalence of vertical facial growth is very high in the developed world. Most authors agree that mouth breathing is its main cause. Even though care is mainly conducted by odontologists, the professionals who first see these patients are pediatricians and otolaryngologists. The objective of this study is to analyze the ability of pediatricians and otolaryngologists to identify early signs of vertical facial growth among children. METHODS: 60 participant aged 4.1-13.7 years were analyzed subjectively by 9 otolaryngologists, 9 pediatricians and two specialists in dentofacial orthopedics. They were also assessed objectively with cephalometric analysis. RESULTS: Otolaryngologists showed 34.78% sensitivity, 92.86% specificity and 48.33% efficiency. Pediatricians showed 13.04% sensitivity, 100% specificity and 33.33% efficiency. Using a linear regression model compared against the objective measurements we found a weak positive correlation both for otolaryngologists and pediatricians. CONCLUSION: The sensitivity was very low for both groups. We believe it is of paramount importance to increase the awareness and the ability of otolaryngologists and pediatricians to recognize signs of disrupt facial growth.