Facial Syndrome Research Articles

Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome.

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 (TBET, STAT1, STAT4), Th2 (GATA3, STAT6), Th17 (RORgt, STAT3), Treg (FoxP3, STAT5) transcription factors and the major cytokines of these cells (Th1; IFNG, Th2; IL4, Th17; IL17A-21-22, Treg; IL10, TGFβ) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients' Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121-2A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.

The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cells via promoting heme synthesis

BackgroundLoss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype–phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells.MethodsWe used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms.ResultsZbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells.ConclusionsZbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Presurgical Maxillary Segmented Orthodontics Associated With 3-Piece Le Fort 1 Osteotomy for Palatal Expansion.

The aim of this study is to assess maxillary transverse dimension following presurgical maxillary segmented orthodontics associated with 3-piece Le Fort 1 osteotomy in a cohort of "long face syndrome" patients with palatal constriction. Patients with maxillary transverse insufficiency were retrospectively included. They all underwent maxillary segmented orthodontics followed by a 3-piece Le Fort 1 osteotomy with palatal expansion. Palatal width dimensions were collected preoperatively, postoperatively, and at the time of the final follow-up, the stability of the expansion was analyzed. Nineteen patients were included. There was no complication. The mean postoperative expansion was 6 mm (range: 3.1-8.7mm) in the canine region and 4.3mm (range: 0-9.1mm) in the second molar region. The mean relapse was 0.36mm (range: 0-1.4mm) or 6% (range: 0%-16.1%) in the canine region and 0.17mm (range: 0-1.3mm) or 4% (range: 0%-14%) in the second molar region. Presurgical maxillary segmented orthodontics with 3-piece Le Fort 1 osteotomy has shown high stability of the maxillary transverse dimension in a 1-step surgery without dental tipping. It should be considered as an alternative to rapid palatal expansion.

CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-electron microscopy structural analysis of the CDCA7-nucleosome complex reveals that the HMZF domain can recognize hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle, whereas UHRF1, the critical activator of the maintenance methyltransferase DNMT1, cannot. CDCA7 recruits HELLS to hemimethylated chromatin and facilitates UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and DNMT1.

Automated Multi-Class Facial Syndrome Classification Using Transfer Learning Techniques.

Genetic disorders affect over 6% of the global population and pose substantial obstacles to healthcare systems. Early identification of these rare facial genetic disorders is essential for managing related medical complexities and health issues. Many people consider the existing screening techniques inadequate, often leading to a diagnosis several years after birth. This study evaluated the efficacy of deep learning-based classifier models for accurately recognizing dysmorphic characteristics using facial photos. This study proposes a multi-class facial syndrome classification framework that encompasses a unique combination of diseases not previously examined together. The study focused on distinguishing between individuals with four specific genetic disorders (Down syndrome, Noonan syndrome, Turner syndrome, and Williams syndrome) and healthy controls. We investigated how well fine-tuning a few well-known convolutional neural network (CNN)-based pre-trained models-including VGG16, ResNet-50, ResNet152, and VGG-Face-worked for the multi-class facial syndrome classification task. We obtained the most encouraging results by adjusting the VGG-Face model. The proposed fine-tuned VGG-Face model not only demonstrated the best performance in this study, but it also performed better than other state-of-the-art pre-trained CNN models for the multi-class facial syndrome classification task. The fine-tuned model achieved both accuracy and an F1-Score of 90%, indicating significant progress in accurately detecting the specified genetic disorders.

Neonatal Leukaemia: A Case Report and Review of the Literature

<i>Background:</i> Acute leukemia has a particularly bad prognosis in the newborn era. Its prognosis is significantly poorer than in older youngsters. The occurrence of leukaemia in the neonatal period can present diagnostic challenges due to the rarity of the condition and its clinical presentation, which may be misleading or inconspicuous. <i>Case report:</i> A case of neonatal acute myeloblastic leukaemia (AML) in a newborn with trisomy 21 is presented herein. The patient was admitted with respiratory distress and a clinical examination revealed a facial dysmorphic syndrome, pallor, hepatosplenomegaly, and a bone marrow failure syndrome with bone marrow invasion by 36% myeloblasts, confirming the diagnosis of AML. The immunophenotyping results indicated that the patient had AML0, with a low CD13+ and CD33+ MPO myeloid population. During the patient's hospitalisation, a multi-resistant Klebsiella pneumoniae urinary tract infection was diagnosed, and septic shock was diagnosed after four days. <i>Conclusion:</i> Acute neonatal leukaemia is a rare and complex condition that requires the expertise of both neonatologists and paediatric haematologists.

Facial Aberrant Reinnervation Syndrome Following Facial Nerve Injury and Recovery.

A common sequela of peripheral nerve injury is aberrant regeneration and recovery. Aberrant regeneration of injured motor nerves can affect all aspects of the nerve circuit from the motor cortex to the target muscle. A more comprehensive term for the symptoms that develop after aberrant motor neuromuscular reinnervation is aberrant reinnervation syndrome (ARS). Injury to the facial nerve followed by aberrant reinnervation results in a spectrum of symptoms that has been called many things in the literature. The authors support that this commonly encountered sequela of facial nerve injury be called facial aberrant reinnervation syndrome (FARS), a term that is more descriptive of the underlying pathophysiology and more inclusive of the clinical symptoms: facial synkinesis, facial muscle hypertonicity, and facial muscle spasm/twitching, which occur following facial nerve injury and recovery. In the following article, we present the clinical manifestations and sequelae of facial nerve injury and recovery and briefly discuss our evolving understanding of the pathophysiology and treatment of FARS.

Femoral Facial Syndrome in an Infant of Diabetic Mother

Femoral Facial Syndrome in an Infant of Diabetic Mother

Exploring Disrupted Gene Networks in Human 22q11.2 Microdeletion

Several deletions are observed at the 22q11 locus and are responsible for 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome, conotruncal anomaly face syndrome, or velocardiofacial syndrome. These microdeletions on human chromosome 22 range from 0.7 to 3 Mb. Many genes are affected by 22q11.2 deletion. However, despite the well-established clinical signs for the diagnosis of 22q11.2 deletion syndrome, the interactome background of 22q11.2 deletion syndrome is unknown. Here, we analyzed protein–protein interaction networks (PPIs) to assess the influences of 3 Mb 22q11.2 deletion on this network. We compared the general human PPI network against a network without 48 genes of the 3 Mb 22q11.2 locus in a homozygous condition: we compared topological metrics, enrichment of gene ontology terms, community assignments, and edge rewiring. The PPI networks revealed that this deletion affected the relevance of hundreds of non-deleted genes. Additionally, this 22q11.2 deletion induces intense rewiring of subnetworks, promoting an accumulation of proteins associated with DiGeorge clinical signs (CTCF, YY1, TFAP2A, PPARG, PAX6, RAX, and E2F3) in a single community (community 1). Therefore, we identified new genes that may be associated with the 22q11.2 deletion syndrome. Altogether, the systemic approaches used here yielded new insights into the 22q11.2 deletion syndrome.

Exploring facial overfilled syndrome from the perspective of anatomy and the mismatched delivery of fillers.

Facial fillers and injectables have transformed the landscape of cosmetic procedures, offering rejuvenation possibilities. However, the emergence of "Facial Overfilled Syndrome (FOS)" presents a concerning trend attributed to excessive filler use and suboptimal injection techniques. Understanding the interplay between facial aging and augmentation techniques is crucial in addressing and preventing FOS. Facial overfilled syndrome is characterized by the excessive use of fillers, resulting in a distorted and heavy appearance. It manifests in various forms, including 'flowerhorn' foreheads, 'sunset' eyes, 'chipmunk' cheeks, 'witch' chins, and 'pillow' faces. The syndrome arises from attempts to combat anatomical aging with dramatic filler treatments, causing rapid volume changes and skin tightening. Skeletal structures and soft tissue distribution across different ethnicities play a significant role in FOS development. Understanding the aging process across facial tissues is essential, as fillers cannot entirely reverse aging manifestations. Tailored assessment and treatment plans should precede filler injections, involving muscle assessment, observation of facial movements during injection, and ultrasound imaging of fat layers. Attention should be given to filler pressure and migration risks, particularly in areas with elevated pressure. Additionally, alternative approaches like energy-based devices and polymer reinforcement of facial ligaments should be considered to minimize filler use. Ethnic variations in facial anatomy require careful consideration to avoid overcorrection. FOS predominantly affects individuals of East Asian descent due to specific facial characteristics. Prevention strategies involve minimizing filler use, addressing underlying bone changes, and considering ethnic and gender differences in facial anatomy. Recent MRI and ultrasound studies challenge the notion of filler breakdown, emphasizing the importance of filler selection and injection techniques. Education, individualized treatments, and a holistic understanding of facial anatomy are key to preventing and managing FOS and ensuring natural and harmonious facial aesthetics.

Congenital asymmetric crying face syndrome: A case of two newborns

Congenital asymmetric crying face syndrome: A case of two newborns

Immunodeficiency, Centromeric Region Instability, Facial Anomalies Syndrome 1

Immunodeficiency, Centromeric Region Instability, Facial Anomalies Syndrome 1

The surgical treatment of velopharyngeal insufficiency in patients with velo cardio facial syndrome

The surgical treatment of velopharyngeal insufficiency in patients with velo cardio facial syndrome

ITPR1-associated spinocerebellar ataxia with craniofacial features-additional evidence for germline mosaicism.

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum-bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement-an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

SAT215 Sagliker Syndrome In A Filipino Female With End Stage Renal Disease

Abstract Disclosure: M.R. Pajanel: None. E. Clarito: None. K. Uytiepo: None. P. De La Peña: None. This is a case of a 29-year-old Filipina, with chronic kidney disease secondary to chronic glomerulonephritis, undergoing hemodialysis for 10 years. She presented with maxillary mass, associated with other craniofacial deformities such as mandibular enlargement and widening of teeth spaces. Other associated symptoms include difficulty in swallowing solid food, difficulty in ambulation due to bone pains, and with noted shortening of stature. Workup revealed elevated intact parathyroid hormone (iPTH) 1638.8pg/mL(20x ULN), low Vitamin D, elevated ALP, but with normal levels of calcium and phosphorus. Sestamibi scan showed focal uptake and retention along medial aspect of the right thyroid bed and inferior to both thyroid beds suggestive of parathyroid adenoma or hyperplasia. Parathyroid ultrasound was consistent with findings of Sestamibi scan which also showed parathyroid nodules in the middle segment right thyroid lobe, and inferior to right thyroid lobe. Bone mineral density is below the expected range for age. Right parathyroidectomy was done and she was discharged well. She came in for follow-up with persistent elevated PTH 4765pg/ml(60x ULN), still with symptoms. Repeat imaging on ultrasound showed a parathyroid nodule posterior to the superior aspect of left thyroid 0.9 x0.5cm. Sestamibi scan confirmed a functioning parathyroid adenoma left inferior and superior thyroid bed. Left parathyroidectomy was done with a histopathologic result of left superior parathyroid consistent with parathyroid hyperplasia. On follow up, repeat intact PTH still elevated at 3677pg/mL and persistently elevated 2 months after at 3626pg/mL. Parathyroid ultrasound showed Parathyroid nodule, left, measuring 1.5x1.7x0.9 cm, inferior and posterior to the inferior border of the left thyroid gland. 99mTc-Sestamibi scan was consistent with the ultrasound in the left thyroid lobe suggestive of parathyroid adenomas or hyperplasia. Completion Parathyroidectomy was done on November 2018. Pre-operative iPTH was 4205pg/mL, which decreased to 291.3pg/mL postoperatively. She was discharged improved. On followup in 2022, she reports of decrease bone pain and now able to ambulate without difficulty. Repeat bone mineral density has improved and now within expected range for age. CONCLUSION: Sagliker syndrome is an entity described as an “uglyfying face syndrome” seen in patients with chronic kidney disease, presenting with facial deformities. Patients usually present with elevated parathyroid hormone (PTH) levels, and has been refractory to medical therapy. Surgical treatment has been the course of approach to prevent further clinical decline of patients. Identification of the syndrome is important for clinicians to know when to maximize medical management, and to identify patients who will benefit with early surgical management. The patient’s quality of life improved even 4 years post-surgery. Presentation: Saturday, June 17, 2023

Treating facial overfilled syndrome with impaired facial expression-Presenting clinical experience with ultrasound imaging.

Facial overfilled syndrome is an adverse event following minimally invasive soft tissue filler injections. It presents in most cases as excess midfacial volume and/or as unnatural smile which is difficult to detect due to the absence of standardized evaluation methods. To showcase how to identify, evaluate, and treat facial overfilled syndrome by utilizing facial ultrasound and simultaneous hyaluronidase injections. Twenty-eight consecutive patients (26 females, 2 males) were enrolled in this study in which facial ultrasound was performed to evaluate the location previously implanted filler material. The position of the oral commissure was objectively measured in relation to bony landmarks, and the severity of lateral canthal lines was assessed by independent and blinded raters. The material was identified in 35.7% inside the subdermal fatty layer, in 28.6% inside the deep supra-periosteal fatty layer, in 10.7% inside the fibrous layer deep to the subdermal fatty layer, whereas in 25.0%, the product was not possible to locate clearly inside one specific layer. On average, 81.6 I.U. [range: 75-150] of hyaluronidase were injected. Lateral canthal line severity was before the treatment 2.28 (1.4) and was after the hyaluronidase treatment 2.02 (1.3) with p = 0.578. The position of the oral commissure increased by 0.60 cm in vertical and by 0.30 cm in horizontal directions (both p < 0.001). Facial overfilled syndrome following aesthetic soft tissue filler injections can present as excess midfacial volume but also as unnatural smile. Targeted hyaluronidase injections into the culprit pockets inside the midfacial soft tissues have shown to re-establish a natural smile, to reduce excess midfacial volume, and to decrease lateral canthal line severity.

Screening newborns for low T cell receptor excision circles (TRECs) Fails to Detect Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome.

Assessment of T-cell receptor excision circles (TRECs) in dried blood spots of newborns allows the detection of severe combined immunodeficiency (SCID) (T cells <300/μL at birth) with a presumed sensitivity of 100%. TREC screening also identifies patients with selected combined immunodeficiency (CID) (T cells >300/μL, yet <1500/μL at birth). Nevertheless, relevant CIDs that would benefit from early recognition and curative treatment pass undetected. We hypothesized that TREC screening at birth cannot identify CIDs that develop with age. We analyzed the number of TRECs in dried blood spots in archived Guthrie cards of 22 children who had been born in the Berlin-Brandenburg area between January 2006 and November 2018 and who had undergone hematopoietic stem-cell transplantation (HSCT) for inborn errors of immunity. All patients with SCID would have been identified by TREC screening, but only 4 of 6 with CID. One of these patients had immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 (ICF2). Two of 3 patients with ICF whom we have been following up at our institution had TREC numbers above the cutoff value suggestive of SCID at birth. Yetall patients with ICF had a severe clinical course that would have justified earlier HSCT. In ICF, naïve T cells may be present at birth, yet they decline with age. Therefore, TREC screening cannot identify these patients. Early recognition is nevertheless crucial, as patients with ICF benefit from HSCT early in life.

Finding its place on the spectrum of pituitary duplication disorders, duplication of pituitary stalk: A case report with brief review of literature.

Pituitary gland duplication is a rare abnormality and isolated duplication of the pituitary stalk without any pituitary anomaly is an even rarer entity with this case being the first documented case till date. Although incidentally discovered cases of duplication of pituitary gland (DPG) have been reported, sometimes with a duplicated pituitary stalk, patients with this disorder usually present with other craniofacial abnormalities. Consequently, DPG plus syndrome is used as it is often accompanied by endocrine disturbances and pathologies such as median cleft face syndrome, ocular disorders, craniocervical bony abnormalities, vascular anomalies and tuberomammillary masses. Since this is the first reported case without any additional pituitary gland anomaly, we propose the acronym DPS (duplication of pituitary stalk) to be used to unify this entity as we are certain that much like the previously described pituitary duplication disorders, more cases will be documented independently rather than under the umbrella of pituitary duplication disorders. This is critical as the life expectancy (age of diagnosis) in the cases reviewed in our study is as good as normal population with no obvious increase in mortality as compared to existing pituitary duplication syndromes. We present a case report of a 2year 7month old girl who was referred by the paediatrician for evaluation of premature thelarche. The duplication of the pituitary stalk along with mega cisterna magna and tuberomammillary fusion was the only positive finding on imaging with the pituitary gland being absolutely normal.

Adenoid hypertrophy-​diagnosis and treatment: the new S2k guideline.

Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with apermanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.

Anesthetic considerations in an infant with femoral hypoplasia‐unusual facies syndrome and Pierre Robin sequence: A case report

Key Clinical MessageFemoral hypoplasia‐unusual facies syndrome is a rare condition of unknown etiology. The phenotype consists of significant femoral hypoplasia with characteristic facial malformations that often overlap with findings seen in patients with Pierre Robin sequence. Anesthesia providers must prepare for difficult intravenous access, difficult airway management, and uncertainties with regional anesthesia.AbstractFemoral hypoplasia‐unusual facies syndrome (FHUFS) or femoral facial syndrome is a rare and sporadic condition of unknown etiology. The phenotype consists of significant femoral hypoplasia with characteristic facial malformations that often overlap with findings seen in patients with Pierre Robin sequence. FHUFS is known to cause challenges with anesthesia, including difficulty with endotracheal intubation. Anesthesia providers must be aware of the possible coexistence of FHUFS and Pierre Robin sequence. They need to prepare for difficult intravenous access, difficult airway management, and uncertainties with regional anesthesia.