Comprehensive management of Crouzon syndrome: A case report with three-year follow-up

2021 ◽  
pp. 146531252110194
Author(s):  
Tulika Tripathi ◽  
Dhirendra Srivastava ◽  
Neha Bhutiani ◽  
Priyank Rai
Keyword(s):  
Present Report ◽  
Growth Factor Receptor ◽  
Upper Airway ◽  
Congenital Deformity ◽  
Crouzon Syndrome ◽  
Comprehensive Management ◽  
Fgfr3 Gene ◽  
Fgfr2 Gene ◽  
And Function

Crouzon syndrome is one of the most common craniosynostosis facial syndromes caused by a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. Less commonly, there is a mutation of the FGFR3 gene which results in Crouzon syndrome syndrome with acanthosis nigricans. It involves the premature fusion of sutures of the cranial vault, base, orbital and maxillary region. The clinical presentation of this congenital deformity depends on the pattern and timing of sutural fusion. The present report describes the features and management of this syndrome in an 18-year-old woman. The patient presented with a hypoplastic maxilla, deficient midface, exorbitism due to shallow orbits, severe crowding and bilateral crossbite. A multidisciplinary approach involving orthodontics and surgical intervention with distraction osteogenesis brought about marked improvement in the facial profile, occlusion and upper airway. The aesthetics and function were greatly enhanced, and the results were found to be stable at the end of three years.

Crouzonodermoskeletal syndrome

2005 ◽  
Vol 28 (2) ◽  
pp. 173-176 ◽  
Author(s):  
A. Jeftha ◽  
L. Stephen ◽  
J. Morkel ◽  
P. Beighton
Keyword(s):  
Acanthosis Nigricans ◽  
Choanal Atresia ◽  
Radiographic Examination ◽  
Molecular Defect ◽  
Shunt Operation ◽  
Crouzon Syndrome ◽  
Genetic Management ◽  
Fgfr3 Gene ◽  
Fgfr2 Gene ◽  
The Status

Crouzon craniostenosis [MIM 123500], is identified on the basis of the additional phenotypical manifestations of acanthosis nigricans, vertebral changes and cementomas of the jaws. Choanal atresia and hydrocephalus are other features. The molecular defect in CDSS is a point mutation in the FGFR3 gene on chromosome 4p, whereas, the mutation in the Crouzon syndrome is in the FGFR2 gene at 10q25.3-26.An affected girl aged 2 years presented at the UWC dental genetics unit with a prior diagnosis of Crouzon syndrome. Choanal atresia had necessitated a permanent tracheostomy, and hydrocephalus was managed by a shunt operation. Clinical examination revealed acanthosis nigricans in the axilliary regions, a diagnosis confirmed by a biopsy of the lesion. Eruption of the primary dentition was delayed with only six out of twenty teeth present. Radiographic examination conducted shortly after birth revealed the presence of several tooth buds in both the maxillae and the mandible. The delayed eruption of the teeth will be of significance in future orthodontic and maxillofacial measures for the improvement of the patient's facial Crouzonodermoskeletal syndrome (CDSS) was separated from the classical appearance. Molecular investigations in the girl and her parents are underway. If the specific mutation in FGFR3 is observed, a positive diagnosis of CDSS will be confirmed and the status of her parents and other family members will be determined. On this basis, appropriate genetic management can be offered to the kindred.

scholarly journals Crouzon syndrome: a case report

2017 ◽  
Vol 5 (1) ◽  
pp. 260
Author(s):  
Gursharn Singh ◽  
Supriya Malik ◽  
Jaskeen Kaur
Keyword(s):  
Fibroblast Growth Factor Receptor ◽  
Genetic Disorder ◽  
Growth Factor Receptor ◽  
Multidisciplinary Management ◽  
Fibroblast Growth ◽  
Crouzon Syndrome ◽  
Radiological Features ◽  
Fgfr2 Gene ◽  
Cranial Deformity ◽  
Clinical Characteristic

Crouzon syndrome is an example of syndromes caused by premature obliteration and ossification of two or more sutures, most commonly coronal and sagittal. Described by a French neurosurgeon in 1912, it is a rare genetic disorder. Crouzon syndrome is caused by mutation in the Fibroblast Growth Factor Receptor 2 (FGFR2) gene. This disorder is characterized by distinctive malformations of skull and face (craniofacial region). Premature cranial suture closure is the most common skull abnormality. The case of an 8-month-old boy with Crouzon syndrome which is one of syndromes associated with synostosis, is presented. He presented in OPD with a cranial deformity, maxillary hypoplasia and exophthalmos. The clinical, characteristic radiological features and investigations carried out, along with treatment of this patient are discussed as part of multidisciplinary management.

Distraction Osteogenesis in the Treatment of Craniofacial Anomalies: Applications and Outcomes

2020 ◽  
Vol 5 (6) ◽  
pp. 1469-1481 ◽  
Author(s):  
Joseph A. Napoli ◽  
Carrie E. Zimmerman ◽  
Linda D. Vallino
Keyword(s):  
Distraction Osteogenesis ◽  
Bone Growth ◽  
Upper Airway ◽  
Craniofacial Anomalies ◽  
Craniofacial Skeleton ◽  
Facial Skeleton ◽  
Psychosocial Impairment ◽  
And Function ◽  
Correct Structure

Purpose Craniofacial anomalies (CFA) often result in growth abnormalities of the facial skeleton adversely affecting function and appearance. The functional problems caused by the structural anomalies include upper airway obstruction, speech abnormalities, feeding difficulty, hearing deficits, dental/occlusal defects, and cognitive and psychosocial impairment. Managing disorders of the craniofacial skeleton has been improved by the technique known as distraction osteogenesis (DO). In DO, new bone growth is stimulated allowing bones to be lengthened without need for bone graft. The purpose of this clinical focus article is to describe the technique and clinical applications and outcomes of DO in CFA. Conclusion Distraction can be applied to various regions of the craniofacial skeleton to correct structure and function. The benefits of this procedure include improved airway, feeding, occlusion, speech, and appearance, resulting in a better quality of life for patients with CFA.

scholarly journals Impact of comprehensive management on clinical outcomes in hypertensive patients with coronary artery disease: HIJ-CREATE sub-study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Ogawa ◽  
H Sekiguchi ◽  
K Jujo ◽  
E Kawada-Watanabe ◽  
H Arashi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Primary Outcome ◽  
Ldl Cholesterol ◽  
Lipid Lowering ◽  
Hypertensive Patients ◽  
Mean Values ◽  
Comprehensive Management ◽  
The Mean ◽  
Artery Disease

Abstract Background There are limited data on the effects of blood pressure (BP) control and lipid lowering in secondary prevention of coronary artery disease (CAD) patients. We report a secondary analysis of the effects of BP control and lipid management in participants of the HIJ-CREATE, a prospective randomized trial. Methods HIJ-CREATE was a multicenter, prospective, randomized, controlled trial that compared the effects of candesartan-based therapy with those of non-ARB-based standard therapy on major adverse cardiac events (MACE; a composite of cardiovascular death, non-fatal myocardial infarction, unstable angina, heart failure, stroke, and other cardiovascular events requiring hospitalization) in 2,049 hypertensive patients with angiographically documented CAD. In both groups, titration of antihypertensive agents was performed to reach the target BP of <130/85 mmHg. The primary endpoint was the time to first MACE. Incidence of endpoint events in addition to biochemistry tests and office BP was determined during the scheduled 6, 12, 24, 36, 48, and 60-month visits. Achieved systolic BP and LDL-Cholesterol (LDL-C) level were defined as the mean values of these measurements in patients who did not develop MACEs and as the mean values of them prior to MACEs in those who developed MACEs during follow-up. Results During a median follow-up of 4.2 years (follow-up rate of 99.6%), the primary outcome occurred in 304 patients (30.3%). Among HIJ-CREATE participants, 905 (44.2%) were prescribed statins on enrollment. Kaplan–Meier curves for the primary outcome revealed that there was no relationship between statin therapy and MACEs in hypertensive patients with CAD. The original HIJ-CREATE population was divided into 9 groups based on equal tertiles based on mean achieved BP and LDL-C during follow-up. For the analysis of subgroups, estimates of relative risk and the associated 95% CIs were generated with a Cox proportional-hazards model (Figure 1). The relation between LDL cholesterol level and hazard ratios for MACEs was nonlinear, with a significant increase of MACEs only in the patients with inadequate controlled LDL-C level even in the patients with tightly controlled BP. Conclusions The results of the post-hoc analysis of the HIJ-CREATE suggest that clinicians should pay careful attention to conduct comprehensive management of lipid lowering even in the contemporary BP lowering for the secondary prevention in hypertensive patients with CAD. Figure 1 Funding Acknowledgement Type of funding source: None

Not All Cases of Mammary Paget’s Disease are Cytokeratin-7 Positive: A Challenging Diagnosis!

2021 ◽  
pp. 106689692110029
Author(s):  
Kerschen Anja ◽  
Dano Hélène ◽  
Van Eeckhout Pascal ◽  
Marot Liliane ◽  
Van Bockstal Mieke
Keyword(s):  
Present Report ◽  
Paget’S Disease ◽  
Growth Factor Receptor ◽  
Punch Biopsy ◽  
Paget's Disease ◽  
Cytokeratin 7 ◽  
In Situ Carcinoma ◽  
Epidermal Growth ◽  
Mammary Paget’S Disease

Mammary Paget’s disease accounts for 1% to 3% of all breast tumors and manifests as a chronic eczematous lesion of the areolar skin. It can occur without any underlying neoplasia or can be present in association with an underlying invasive and/or in situ carcinoma of the breast. The present report describes a challenging nipple punch biopsy showing an infiltration of the lower third to two-thirds of the epidermis by large, ovoid, neoplastic cells. The morphology was consistent with mammary Paget's disease, although immunohistochemistry for cytokeratin-7 (CK7) was repeatedly negative. This resulted in an initial misdiagnosis and, subsequently, a delay in the patient's follow-up. Additional immunohistochemistry for GATA binding protein 3 (GATA3) and human epidermal growth factor receptor 2 (HER2), as well as a second opinion of a breast pathologist, resulted in the diagnosis of mammary Paget's disease. The aim of this article is to raise awareness among pathologists and prevent them from misdiagnosing CK7-negative Paget disease of the breast.

scholarly journals PDGFRα: Expression and Function during Mitral Valve Morphogenesis

2021 ◽  
Vol 8 (3) ◽  
pp. 28
Author(s):  
Kelsey Moore ◽  
Diana Fulmer ◽  
Lilong Guo ◽  
Natalie Koren ◽  
Janiece Glover ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Primary Cilia ◽  
Growth Factor Receptor ◽  
Akt Phosphorylation ◽  
Valve Development ◽  
Biochemical Assays ◽  
Factor Receptor Alpha ◽  
Mesenchymal Transformation ◽  
And Function

Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the role of platelet-derived growth factor receptor-alpha (PDGFRα), a receptor known to be present on the primary cilium, during valve development using genetically modified mice, biochemical assays, and high-resolution microscopy. While PDGFRα is expressed throughout the ciliated valve interstitium early in development, its expression becomes restricted on the valve endocardium by birth and through adulthood. Conditional ablation of Pdgfra with Nfatc1-enhancer Cre led to significantly enlarged and hypercellular anterior leaflets with disrupted endothelial adhesions, activated ERK1/2, and a dysregulated extracellular matrix. In vitro culture experiments confirmed a role in suppressing ERK1/2 activation while promoting AKT phosphorylation. These data suggest that PDGFRα functions to suppress mesenchymal transformation and disease phenotypes by stabilizing the valve endocardium through an AKT/ERK pathway.

scholarly journals FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma

2020 ◽  
Author(s):  
Jens Schittenhelm ◽  
Lukas Ziegler ◽  
Jan Sperveslage ◽  
Michel Mittelbronn ◽  
David Capper ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Diagnostic Tools ◽  
Wild Type ◽  
Rt Pcr ◽  
Fgfr3 Gene ◽  
Detection Tool ◽  
Sequence Variations ◽  
Gene Panel Sequencing

Abstract Background Fibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear. Methods We performed RT-PCR in 101 glioblastoma samples to detect FGFR3-TACC3 fusions (“RT-PCR cohort”) and correlated results with FGFR3 immunohistochemistry (IHC). Further, we applied FGFR3 IHC in 552 tissue microarray glioma samples (“TMA cohort”) and validated these results in two external cohorts with 319 patients. Gene panel sequencing was carried out in 88 samples (“NGS cohort”) to identify other possible FGFR3 alterations. Molecular modeling was performed on newly detected mutations. Results In the “RT-PCR cohort,” we identified FGFR3-TACC3 fusions in 2/101 glioblastomas. Positive IHC staining was observed in 73/1024 tumor samples of which 10 were strongly positive. In the “NGS cohort,” we identified FGFR3 fusions in 9/88 cases, FGFR3 amplification in 2/88 cases, and FGFR3 gene mutations in 7/88 cases in targeted sequencing. All FGFR3 fusions and amplifications and a novel FGFR3 K649R missense mutation were associated with FGFR3 overexpression (sensitivity and specificity of 93% and 95%, respectively, at cutoff IHC score > 7). Modeling of these data indicated that Tyr647, a residue phosphorylated as a part of FGFR3 activation, is affected by the K649R mutation. Conclusions FGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.

Impact of rhythm in non-valvular atrial fibrillation on four cardiac chamber deformation imaging

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Philabout ◽  
L Soulat-Dufour ◽  
I Benhamou-Tarallo ◽  
S Lang ◽  
S Ederhy ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Cardiac Rhythm ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Cardiac Chamber ◽  
Deformation Imaging ◽  
And Function

Abstract Background Few studies have assessed the evolution of cardiac chambers deformation imaging in patients with atrial fibrillation (AF) according to cardiac rhythm outcome. Purpose To evaluate cardiac chamber deformation imaging in patients admitted for AF and the evolution at 6-month follow-up (M6). Methods In forty-one consecutive patients hospitalised for AF two-dimensional transthoracic echocardiography was performed at admission (M0) and after six months (M6) of follow up. In addition to the usual parameters of chamber size and function, chamber deformation imaging was obtained including global left atrium (LA) and right atrium (RA) reservoir strain, global left ventricular (LV) and right ventricular (RV) free wall longitudinal strain. Patients were divided into three groups according to their cardiac rhythm at M0 and M6: AF at M0 and sinus rhythm (SR) at M6 (AF-SR) (n=23), AF at M0 and AF at M6 (AF-AF) (n=11), SR at M0 (spontaneous conversion before the first echocardiography exam) and SR in M6 (SR-SR) (n=7) Results In comparison with SR patients (n=7), at M0, AF patients (n=34)) had lower global LA reservoir strain (+5.2 (+0.4 to 12.8) versus +33.2 (+27.0 to +51.5)%; p<0.001), lower global RA reservoir strain (+8.6 (−5.4 to 11.6) versus +24.3 (+12.3 to +44.9)%; p<0.001), lower global LV longitudinal strain (respectively −12.8 (−15.2 to −10.4) versus −19.1 (−21.8 to −18.3)%; p<0.001) and lower global RV longitudinal strain (respectively −14.2 (−17.3 to −10.7) versus −23.8 (−31.1 to −16.2)%; p=0.001). When compared with the AF-SR group at M0 the AF-AF group had no significant differences with regard to global LA and RA reservoir strain, global LV and RV longitudinal strain (Table). Between M0 and M6 there was a significant improvement in global longitudinal strain of the four chambers in the AF-SR group whereas no improvements were noted in the AF-AF and SR-SR group (Figure). Conclusion Initial atrial and ventricular deformations were not associated with rhythm outcome at six-month follow up in AF. The improvement in strain in all four chambers strain suggests global reverse remodelling all cardiac cavities with the restoration of sinus rhythm. Evolution of strain between M0 and M6 Funding Acknowledgement Type of funding source: None

scholarly journals POS0514 IMPORTANCE OF BODY MASS MEASUREMENT AND THE GRIP STRENGTH TEST TO PREDICT FALLS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 491.2-491
Author(s):  
M. Tada ◽  
Y. Yamada ◽  
K. Mandai ◽  
N. Hidaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Survival Rate ◽  
Grip Strength ◽  
Muscle Mass ◽  
Curve Analysis ◽  
Roc Curve Analysis ◽  
Free Survival ◽  
Leg Muscle ◽  
And Function

Background:We previously reported that the prevalence of sarcopenia was 28% in patients with rheumatoid arthritis (RA) in a cohort study 1. RA patients have a high risk of falls and fractures 2. However, the predictors of falls and fractures in RA patients are not known.Objectives:Whether evaluation of muscle mass and function at baseline could predict falls and fractures during four-year follow-up was investigated.Methods:The four-year follow-up data from a prospective, observational study (CHIKARA study: Correlation researcH of sarcopenIa, sKeletal muscle and disease Activity in Rheumatoid Arthritis) were used. Muscle mass was measured by a body impedance analyzer, and leg muscle mass was calculated. The leg muscle score (max: 100, min: 0) reflected the ratio of leg muscle mass to overall weight. Grip strength as an indicator of muscle function was evaluated using a digital, hand-held, isokinetic dynamometer. The correlations between muscle mass or function and falls or fractures were analyzed by survival rates and Cox hazard ratios. Leg muscle mass and grip strength were investigated by receiver operating characteristic (ROC) curve analysis for correlations with falls or fractures.Results:A total of 100 RA patients (female: 78%, mean age: 66.1 years) were enrolled; 35 patients had falls, and 19 patients had fractures during the four-year follow-up. The leg muscle score, grip strength, age, and fractures at baseline were significantly correlated with falls. The cut-off values of the leg muscle score and grip strength were calculated to be 84.5 points (sensitivity: 0.79, specificity: 0.43) and 15.9 kg (sensitivity: 0.56, specificity: 0.70), respectively, by ROC curve analysis. The patients were divided into four groups by their leg muscle scores and grip strength; the numbers of falls and fractures are shown in Table 1 for each group. The fall-free survival rate was significantly lower in the group with low leg muscle score and low grip strength (35.3%) than in the other groups (P=0.002) (Figure 1). The hazard ratio for the both low group was significantly increased, 3.6-fold (95%CI: 1.1-11.5), compared to that in the both high group.Table 1.Numbers of falls and fractures by category of leg muscle score and grip strengthLG + GS+(n=34)LG - GS+(n=12)LG + GS-(n=37)LG - GS-(n=17)P value*Falls, N6515110.010Fractures, N34660.072LG+: leg muscle score >84.5 points, GS+: grip strength >15.9kg, LG-: leg muscle score ≤84.5 points, GS+: grip strength ≤15.9kg*: compared in four groups by Kruskal-Walls test.Figure 1.Fall-free survival rate in the four groupsConclusion:RA patients with both low leg muscle score and low grip strength at baseline were at high risk for falls during the four-year follow-up period. Evaluation of muscle mass and function can predict falls in RA patients.References:[1]Tada, M., Yamada, Y., Mandai, K. & Hidaka, N. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis21, 1962-1969, doi:10.1111/1756-185X.13335 (2018).[2]van Staa, T. P., Geusens, P., Bijlsma, J. W., Leufkens, H. G. & Cooper, C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum54, 3104-3112, doi:10.1002/art.22117 (2006).Disclosure of Interests:None declared

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