Syndromic Patients Research Articles

Assessing the factors that influence a recurrence of congenital talipes equinovarus in children treated with the Ponseti method

Background: Congenital talipes equinovarus, also known as clubfoot, is one of the most common congenital malformations in pediatric orthopedics. With a checkered treatment history extending from Hippocrates' bandages to Kite's serial plaster cast application to surgical treatment, no single modality can claim to be a complete treatment. Methods: In a combined prospective and retrospective study at the Department of Orthopaedics of St. Stephen's Hospital, 192 patients with 292 clubfeet who met the inclusion criteria and received ethics committee approval were included. The purpose of the research was to identify early recurrence characteristics, undertake the Pirani scoring, and identify additional clinical characteristics to evaluate recurrence predictors. Results: In our study, out of 192 patients, 188 were successfully treated with the Ponseti casting technique combined with tendoachilles tenotomy; tenotomy was required in 177 patients (93%). Four patients were lost to follow-up. Nine out of sixty-one children in the six-month-to-one-year age group showed the maximum rate of recurrence (15%). The mean number of cast applications was 7.23. In all, 90% of children required casts ranging from four to eight in number. The syndromic association was seen in 10.4% of cases with club feet. Most common among them were neural tube defects (4.2%) and arthrogryposis (3% of cases). Fourteen out of 154 (or 9%) of the non-operated idiopathic patients had lateral border recurrence during an average follow-up of two years. According to the Pirani score, recurrence was seen in eight out of twenty (or 40% of) syndromic patients and five out of fourteen (or 35% of) operated cases. In 37% of recurrences, dynamic supination was observed. Conclusions: Even though Ponseti's approach to treating idiopathic clubfoot is widely regarded as the gold standard, recurrences are known to occur even in the best of circumstances. The most common cause of recurrence was poor brace compliance, with families citing a variety of reasons.

Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se. We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6–71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2–4; range 2–27) during a median of 4.0 years (IQR: 2.3–6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0–62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI95: 1.87–1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 1.70–1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age (p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group.

Recurrence Patterns of Odontogenic Keratocysts in Syndromic and Non-Syndromic Patients.

Odontogenic keratocysts (OKCs) have high recurrence rates. We aimed to identify recurrence patterns in OKCs and the onset of second primary OKCs in non-syndromic and syndromic patients. Patients with OKCs reporting to our department from 1998 to 2021 (23years) were retrospectively evaluated using demographic, clinical (age, sex, location, and size), histopathological, radiographic, and treatment data. All patients were followed-up for > 3years and evaluated for OKC recurrence. Patients with naevoid basal cell carcinoma syndrome (NBCCS) were evaluated separately. We included 38 and 13 patients in the non-syndromic and syndromic OKC groups, respectively. The recurrence rates were 15.8 and 21.4% in the non-syndromic and syndromic groups, respectively; 8.9% of patients exhibited a second recurrence and 1.8% a third recurrence. No second primary OKCs were observed in the non-syndromic group; 76.9% of patients in the syndromic group developed at least one. We found a higher recurrence rate in patients with NBCCS compared with patients with non-syndromic OKCs (21.4 versus 15.8%). The probability of developing a second primary OKC in patients with NBCCS was higher compared with that in patients with non-syndromic OKCs (76.9 versus 0%). No statistically significant risk factors for OKC recurrence were identified.

Roadmap for daily practice of CBCT in cleft lip palate paediatric patients: a pictorial review.

Objective: to present and to illustrate a new methodology for daily practice in cone beam computed tomography (CBCT) interpretation and reporting in cleft lip palate (CLP) non syndromic paediatric patients. The proposed protocol is based on clinical experience and on systematic search of the literature. Material and methods: We performed two types of systematic search of articles: 1) articles related to the use of CBCT in CLP patients, and 2) articles related to the reporting and interpretation of the CBCT images by radiologists. We used two databases PubMed and Google scholar. Results: For indications of CBCT in CLP patients we found in PubMed 378 articles and 48 articles were selected for the review; in Google scholar we found 463 articles, and 9 articles were selected for the review. 2) For reporting in CBCT we found 956 articles in PubMed, and 9 articles were selected for the review. Conclusions: We presented the 6-steps system for interpretation and reporting information from CBCT of CLP paediatric patients: 1) Step 1 (axial view): presence or absence of bone bridge remnants of alveolar bone graft; Step 2 (3D dental tissue reconstruction): description of dental arch tooth by tooth, search for agenesis and supernumerary teeth, description of variation in the position of the tooth explaining the type of existing translation and rotation; Step 3 (coronal view): cleft palate pathway and its extension; anomaly in maxillary, ethmoid and sphenoid sinuses if existing; Step 4 (sagittal and coronal view): checking of the opening (calcification sites) of the sphenooccipital synchondrosis, and checking of anomalies of the occipital bone; Step 5 (3D bone tissue reconstruction): C1-C2 vertebra anomalies; Step 6 (3D soft tissue reconstruction): external ear anomalies. We illustrated our methodology with 46 figures from 5 CBCT of CLP patients.

Posterior Cranial Distraction in Craniosynostosis: A Systematic Review of the Literature.

Posterior cranial distraction (PCD) is a surgical technique to address craniosynostosis, especially in syndromic patients. The technique has the ability to significantly expand the cranium, while requiring minimal dural dissection, compared to cranial remodeling. Our goals were to determine the patient characteristics and surgical outcomes of PCD. The two questions that we sought to answer were: 1) What is the average published complication rate and the most common complications of PCD? and 2) How much intracranial volume expansion can one expect with PCD? A PubMed database search of articles on PCD was performed. Case reports and articles with overlapping patients were excluded. A systematic review was performed using the remaining articles. Patient data were extracted in order to determine the total number of patients, patients with a syndrome, types of syndromes, mean age at surgery, mean distraction distance, mean increase in intracranial volume, and complications. 18 articles representing 325 patients were analyzed. A syndrome was present in 68.6% of patients. The mean age at time of surgery was 22.1 months. Mean distraction amount was 24.7 mm. Mean increase in intracranial volume was 253.2 cm3. The overall complication rate was 32.2%, with the most common complications being surgical-site infection, hardware-related complications and delayed wound healing. PCD is a powerful technique in the management of syndromic craniosynostosis, although complication rates are significantly higher than traditional remodeling techniques. Future studies should compare the effects of supratorcular and infratorcular osteotomies on intracranial volume, cosmesis and complications.

Three-dimensional radiographic features of craniometaphyseal dysplasia—a comparative CBCT study

PurposeCraniometaphyseal dysplasia (CMD) is a rare skeletal disorder that has progressive thickening and increased density of the craniofacial bones along with abnormal metaphyses of the long bones. Other features include a wide nasal bridge, paranasal bossing, hypertelorism, and an increase in the zygomatic width. We present a series of cases that showcase the three-dimensional radiographic features of this rare condition and compare it with an age and gender-matched controlled group using cone beam computed tomography (CBCT).ObjectiveTo evaluate the three-dimensional radiographic features of craniometaphyseal dysplasia (CMD).Materials and methodsRetrospective analysis of CBCT scans of 7 patients who were diagnosed with the rare condition craniometaphyseal dysplasia was evaluated. Radiographic features of the craniofacial bones, the paranasal sinuses prominently maxillary, and frontal and sphenoid sinuses were evaluated. Skull bones were also evaluated, and the size and shape of the sella turcica and external auditory meatus were measured. Retained primary teeth and impactions were evaluated using a panoramic reformatted image. The type of occlusion and buccolingual dimensions of jaw bones were also assessed. Age and gender-matched control samples were used to measure the same features for comparing CMD patients to healthy controls. The quality of normal and syndromic patients’ cortical and trabecular bone was determined by measuring pixel intensity values (PIV) generated by CBCT scans.ResultsCone beam CT images of patients with CMD were analyzed to evaluate cranial bones, their density, and any abnormalities associated with the sinuses and foramina. Patients with CMD had bones increased in size. A significant increase in the amount of bone formed was found in the inner table of the frontal and occipital bones. All seven patients with CMD had smaller foramina due to the deposition of sclerosed bone in the foramina of the skull base. The paranasal sinuses, prominently maxillary and frontal and sphenoid sinuses, were smaller than the age and gender-matched controls. The buccolingual dimensions of jawbones were increased. The maxillary and mandibular arch relationship ranged from class II to class III. The mean nasal bridge measurement for the CMD patients was 26.77 mm, while in the controls, the mean nasal bridge measurement was 19.48 mm. The mean measurements of the right and left orbits of CMD patients were 30.6 mm and 31.07 mm respectively, and the mean measurements of the right and left orbits of controls were 32.45 mm and 32.04 mm. Pixel intensity values (PIVs) representing density ranged between 100 and 1000 PIVs for cortical bone and between − 60 and 258 for trabecular bone suggesting a densely sclerotic texture, while in the control group patients, the PIVs for cortical bone were > 1000 and 150–300 for trabecular bone.ConclusionCMD patients had significantly larger bone widths, a lower density of the bone, and smaller sinuses compared to the control group.

Successful airway management in a child with Edward's syndrome: A case report

The airway management of syndromic pediatric patients is an ongoing challenge for the anesthesiologist. The craniofacial abnormalities and multiple system anomalies in Edward syndrome children require special consideration during the perioperative period. We hereby report the successful airway management of an 8-year-old male child with Edward’s syndrome posted for laparoscopic orchidopexy.

Postoperative computed tomography imaging of pediatric patients with craniosynostosis: radiation dose and image quality comparison between multi-slice computed tomography and O-arm cone-beam computed tomography

BackgroundWhen postoperative multi-slice computed tomography (MSCT) imaging of patients with craniosynostosis is used, it is usually performed a few days after surgery in a radiology department. This requires additional anesthesia for the patient. Recently, intraoperative mobile cone-beam CT (CBCT) devices have gained popularity for orthopedic and neurosurgical procedures, which allows postoperative CT imaging in the operating room.ObjectiveThis single-center retrospective study compared radiation dose and image quality of postoperative imaging performed using conventional MSCT scanners and O-arm CBCT.Materials and methodsA total of 104 pediatric syndromic and non-syndromic patients who were operated on because of single- or multiple-suture craniosynostosis were included in this study. The mean volumetric CT dose index (CTDIvol) and dose-length product (DLP) values of optimized craniosynostosis CT examinations (58 MSCT and 46 CBCT) were compared. Two surgeons evaluated the subjective image quality.ResultsCBCT resulted in significantly lower CTDIvol (up to 14%) and DLP (up to 33%) compared to MSCT. Multi-slice CT image quality was considered superior to CBCT scans. However, all scans were considered to be of sufficient quality for diagnosis.ConclusionThe O-arm device allowed for an immediate postoperative CBCT examination in the operating theater using the same anesthesia induction. Radiation exposure was lower in CBCT compared to MSCT scans, thus further encouraging the use of O-arms. Cone-beam CT imaging with an O-arm is a feasible method for postoperative craniosynostosis imaging, yielding less anesthesia to patients, lower health costs and the possibility to immediately evaluate results of the surgical operation.

Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.

Clinical Outcomes of Orchiopexy for Undescended Testes in Syndromic Patients with Developmental Delay, Genetic Syndromes, and Congenital Anomalies

Clinical Outcomes of Orchiopexy for Undescended Testes in Syndromic Patients with Developmental Delay, Genetic Syndromes, and Congenital Anomalies

The Need for Additional Surgery after Passive versus Active Approaches to Syndromic Craniosynostosis: A Meta-analysis

PubMed and Embase were searched in June 2022 to identify all articles reporting primary reoperation or Whitaker outcomes for syndromic patients undergoing cranial vault expanding surgery or suturectomy. A meta-analysis of proportions was performed comparing UORs, and a trim-and-fill adjustment method was used to validate sensitivity and assess publication bias. A total of 721 articles were screened. Five EACS articles (83 patients) and 22 active approach articles (478 patients) met inclusion criteria. Average UORs for EACS and active approaches were 26% (14%-38%) and 20% (13%-28%), respectively (P = 0.18). Reoperation occurred earlier in EACS patients (13.7 months postprimary surgery versus 37.1 months for active approaches, P = 0.003). Relapse presentations and reason for reoperation were also reviewed. Subjectively, EACS UORs were higher in all syndromes except Apert, and Saethre-Chotzen patients had the highest UOR for both approaches. There was no statistically significant increase in UORs among syndromic patients treated with EACS compared with traditional approaches, although EACS patients required revision significantly sooner. Uncertainties regarding the long-term efficacy of EACS in children with syndromic craniosynostosis should be revisited as more data become available.

Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API)

BackgroundT-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019.MethodsChildren with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years.ResultsAmong 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result.ConclusionThe German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.

Long-term speech outcome in patients with Robin sequence after cleft palate repair and tongue-lip adhesion: A 21-year retrospective analysis

The purpose of this study was to assess the effect of tongue−lip adhesion (TLA) on the long-term speech and articulation outcomes of patients with Robin sequence (RS) after cleft palate repair. Outcomes were compared to those in patients with RS who required positioning alone and to patients with isolated cleft palate (ICP).All consecutive patients with RS (with or without TLA) versus isolated cleft palate (ICP) who underwent cleft palate repair were retrospectively reviewed. Speech and articulation included all assessments between the age of 3–6 years. Secondary speech operations, velopharyngeal insufficiency (VPI), hypernasality, and articulation errors by cleft-type characteristics (CTC), including 4 categories (passive), non-oral, anterior-oral, and posterior-oral. A total of 41 RS patients and 61 ICP patients underwent repair with sufficient follow-up. Of them, 23 patients underwent a TLA at median age of 12 days. Rates of hypernasality (p = 0.004), secondary speech operations (p = 0.004), and posterior oral CTC (p = 0.042) were higher in RS compared to ICP. Isolated RS had speech outcomes similar to those of ICP; however, syndromic RS patients needed more secondary speech operations compared to isolated RS (p = 0.043). TLA-RS patients did not demonstrate differences in speech outcomes or any CTCs (all p > 0.05) compared to non−TLA-RS patients, except for the anterior oral CTC (74% TLA-RS vs 28% non−TLA-RS, p = 0.005).Within the limitations of the study, it seem that TLA does not affect long-term velopharyngeal function in patients with RS. However, TLA-RS patients demonstrated higher rates of anterior-oral CTC, which might be related to a different positioning of the tongue after TLA. Every effort should be taken to treat patients with RS conservatively instead of with TLA because of this demonstrated a negative effect on one type of articulation error. However, if conservative therapy fails, a TLA is still a valuable adjunct in the treatment of RS, and cleft speech pathologists who treat such patients should be more aware of this phenomenon in order to improve long-term articulation outcomes.

Practical Algorithm for the Management of Multisutural Craniosynostosis with Associated Chiari Malformation and/or Hydrocephalus

Introduction: The association between multisutural craniosynostosis with Chiari malformation (CM), venous hypertension, and hydrocephalus is widely described in the literature, especially in children with paediatric craniofacial syndromes. Some efforts have been done in the last years to understand the complex pathogenetic mechanisms underlying this association, and several theories have been proposed. In particular, it is now accepted that the hypothesis of the overcrowding of the posterior fossa due to precocious suture fusion is the cause of the cerebellar herniation in syndromic and non-syndromic patients, against the theory of intrinsic cerebellar anomalies, ventriculomegaly, and venous hypertension. However, whatever the pathophysiological mechanism, it is still unclear what the best management and treatment of CM and hydrocephalus are in multisutural craniosynostosis patients. The aim of this study was to report our 25 years’ experience in treating paediatric patients affected by these rare pathologies in order to propose a simple and effective therapeutic flow chart for their management. Materials and Methods: We retrospectively collected data of each patient who underwent a cranial vault remodelling (CVR) for complex multisutural craniosynostosis in our institution in the last 25 years, while monosutural craniosynostosis was excluded. We recorded data concerning type of craniosynostosis and craniofacial syndromes, presence of ventriculomegaly, and CM at presentation and clinical and radiological follow-up. Therefore, we evaluated the final outcomes (improved, stable, deteriorated) of these patients and created a practical flow chart that could help physicians choose the best surgical treatment when different pathological conditions, as Chiari malformation I (CMI) or hydrocephalus, affect complex craniosynostosis children. Results: Thirty-nine patients (39 out of 55; 70.9%), with an isolated multisutural craniosynostosis at presentation, underwent a two-step CVR as first surgery; 36 patients (92.3%) had an improved outcome, 2 patients (5.1%) had a stable outcome, and 1 patient (2.56%) had a deteriorated outcome. Other eight children (8 out of 55; 14.5%) had a radiological evidence of asymptomatic CMI at presentation. In this group, we performed CVR as first surgery. As for the final outcome, 7 patients had an improved outcome (87.5%) with good aesthetic result and stability or resolution of CMI. Finally, 7 patients (7 out of 55; 12.7%) presented a various combination of CMI and ventriculomegaly or hydrocephalus at presentation. Among them, 3 patients had an improved outcome (42.8%), and 4 patients had a deteriorated outcome (57.1%). Discussion: The prevalence of one pathological condition with associated symptoms over the others was the key factor leading our therapeutic strategy. When craniosynostosis is associated with a radiological CM, the assessment of clinical symptoms is of capital importance. When asymptomatic or pauci-symptomatic, we suggest a CVR as first step, for its efficacy in reducing tonsillar herniation and solving CM symptoms. When craniosynostosis is associated with ventricular enlargement, the presence of intracranial hypertension signs and symptoms forces physicians to first treat hydrocephalus with a ventriculo-peritoneal shunt or endoscopic third ventriculostomy. For patients with various degrees and severity of ventriculomegaly and associated CM, the outcomes were very heterogeneous, even when the same therapeutic strategy was applied to patients with similar starting conditions and symptoms. This is maybe the most unexpected and least clear part of our results. Despite the proposed algorithm comes from a clinical experience on 85% successfully treated patients with multiple craniosynostosis, more extensive and deep studies are needed to better understand CM and hydrocephalus development in such conditions.

Long Term Study of Otitis Media with Effusion after Palatoplasty and Myringotomy with Ventilation Tube Insertion

Objective: To identify the incidence of recurrent otitis media in cleft palate patients after palatoplasty and myringotomy \14 ";"&gt;with ventilation tube (VT) insertion in addition to identifying risk factors of recurrent otitis media with effusion (OME). Material and Methods: This retrospective cohort study was conducted from; January 2002 – December 2014. A total of 120 non- syndromic cleft palate patients were included and analyzed for risk factors contributing to recurrent otitis \14 ";"&gt;media with effusion. Results: \14 ";"&gt;In total, 77.5% of the VT slipped off at 10 months after their initial operation. The incidence of recurrent OME was 54.2% at 7 months after VT slipped off. Significant risk factors that were associated to recurrent OME included: complete cleft palate, two-stage palatoplasty and VT slip-off (p-value&lt;0.05). Conclusion: \14 ";"&gt;The incidence of recurrence OME was 54.2%, and risk factors for recurrence OME are VT slipped off, complete cleft palate and two-stage palatoplasty.

A 20-Year Retrospective Study of Children and Adolescents Treated by the Three-in-One Procedure for Patellar Realignment.

Patellar instability is the most common disorder of the knee during childhood and adolescence. Surgical treatment significantly reduces the rate of redislocation, but the underlying pathologies and pattern of instability may affect the results. We aimed to report the clinical and functional outcomes of the three-in-one procedure for patellar realignment in a cohort of skeletally immature patients with or without syndromes and various patterns of chronic patellar instability. We retrospectively investigated 126 skeletally immature patients (168 knees) affected by idiopathic or syndromic patellar instability, who underwent patella realignment through a three-in-one procedure. We classified the instability according to the score proposed by Parikh and Lykissas. Patellar dislocation was idiopathic in 71 patients (94 knees; 56.0%) and syndromic in 55 (74 knees; 44.0%). The mean age at surgery was 11.5 years (range 4-18) and was significantly lower in syndromic patients. Syndromic patients also exhibited more severe clinical pattern at presentation, based on the Parikh and Lykissas score. The mean follow-up was 5.3 years (range 1.0-15.4). Redislocation occurred in 19 cases, with 10 cases requiring further realignment. The Parikh and Lykissas score and the presence of congenital ligamentous laxity were independent predictors of failure. A total of 22 knees in 18 patients required additional surgical procedures. The post-operative Kujala score was significantly lower in patients with syndromic patellar instability. The type of instability and the presence of underlying syndromes negatively affect the rate of redislocation and the clinical and functional outcome following patellar realignment through the three-in-one procedure. We recommend the consideration of alternative surgical strategies, especially in children with severe syndromic patellar dislocation.

Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2.

AIM2 is a key cytoplasmatic pathogen-sensor that detects foreign DNA from viruses and bacteria; it can also recognize damaged or anomalous presence of DNA, promoting inflammasome assembly and activation with the secretion of IL-1β, thus sustaining a chronic inflammatory state, potentially leading to the onset of autoinflammatory skin diseases. Given the implication of the IL-1β pathway in the pathogenesis of syndromic hidradenitis suppurativa (HS), an autoinflammatory immune-mediated skin condition, the potential involvement of AIM2 was investigated. Sequencing of the whole coding region of the AIM2 gene, comprising 5'- and 3' UTR and a region upstream of the first exon of ~800 bp was performed in twelve syndromic HS patients. Six out of twelve syndromic HS patients carried a heterozygous variant c.-208 A ≥ C (rs41264459), located on the promoter region of the AIM2 gene, with a minor allele frequency of 0.25, which is much higher than that reported in 1000 G and GnomAD (0.075 and 0.094, respectively). The same variant was found at a lower allelic frequency in sporadic HS and isolated pyoderma gangrenosum (PG) (0.125 and 0.065, respectively). Our data suggest that this variant might play a role in susceptibility to develop syndromic forms of HS but not to progress to sporadic HS and PG. Furthermore, epigenetic and/or somatic variations could affect AIM2 expression leading to different, context-dependent responses.

Comparative Molecular Genetics of Odontogenic Keratocysts in Sporadic and Syndromic Patients

Odontogenic keratocysts (OKCs) are common cysts of odontogenic origin that usually occur as a single nonsyndromic cyst in isolation (sporadic) or as syndromic multiple cysts as a manifestation of naevoid basal cell carcinoma syndrome. Alterations involving the PTCH gene are the most commonly identified factor associated with up to 85% and 84% of naevoid basal cell carcinoma syndrome and sporadic cases, respectively. Other Hedgehog pathway and non-Hedgehog pathway-associated genes have been implicated in the pathogenesis of OKCs. This pilot study used the Affymetrix OncoScan molecular assay to perform a comparative genomic analysis between 4 sporadic and 3 syndromic cases of OKC to identify molecular drivers that may be common and/or distinct in these 2 groups. The majority of alterations detected in both groups were copy number neutral loss of heterozygosity. Despite distinct molecular signatures observed in both groups, copy number neutral loss of heterozygosity alterations involving chromosome 9q affecting not only PTCH but also the NOTCH1 gene were detected in all syndromic and 3 sporadic cases. Loss of heterozygosity alterations involving 16p11.2 affecting genes not previously described in OKCs were also detected in all syndromic and 3 sporadic cases. Furthermore, alterations on 22q11.23 and 10q22.1 were also detected in both groups. Of note, alterations on 1p13.3, 2q22.1, and 6p21.33 detected in sporadic cases were absent in all syndromic cases. This study demonstrates that a more common group of genes may be affected in both groups of OKCs, whereas other alterations may be useful in distinguishing sporadic from syndromic cysts. These findings should be validated in larger OKC cohorts to improve molecular diagnosis and subsequent patient management.

Randomized controlled trial to evaluate the effect of prophylactic amiodarone versus dexmedetomidine on reducing the incidence of postoperative junctional ectopic tachycardia after pediatric open heart surgery.

Junctional ectopic tachycardia (JET) is the most common arrhythmia after pediatric open-heart surgeries (OHS), causing high morbidity and mortality. As diagnosis is often missed in patients with minimal hemodynamic instability, its incidence depends on active surveillance. A prospective randomized trial evaluated the efficacy and safety of prophylactic amiodarone and dexmedetomidine to prevent and control postoperative JET. Consecutive patients aged under 12 years were randomized into amiodarone, dexmedetomidine (initiated during anesthetic induction) and control groups. Outcome measures included incidence of JET, inotropic score, ventilation, and intensive care unit (ICU) duration and hospital stay, as well as adverse drug effects. Two hundred and twenty-five consecutive patients with a median age of 9 months (range 2 days-144 months) and a median weight of 6.3 kg (range 1.8 kg-38 kg) were randomized with 70 patients each to amiodarone and dexmedetomidine groups, and the rest were controls. Ventricular septal defect and Fallot's tetralogy were the common defects. The overall incidence of JET was 16.4%. Syndromic patients, hypokalemia, hypomagnesemia, longer bypass, and cross-clamp duration were the risk factors for JET. Patients with JET had significantly prolonged ventilation (P = 0.043), longer ICU (P = 0.004), and hospital stay (P = 0.034) than those without JET. JET was less frequent in amiodarone (8.5%) and dexmedetomidine (14.2%) groups compared to controls (24.7%) (P = 0.022). Patients receiving amiodarone and dexmedetomidine had significantly lower inotropic requirements, lower ventilation duration (P = 0.008), ICU (P = 0.006), and hospital stay (P = 0.05). Adverse effects such as bradycardia and hypotension after amiodarone and ventricular dysfunction after dexmedetomidine were not significantly different from controls. Prophylactic amiodarone or dexmedetomidine started before OHS is effective and safe for the prevention of postoperative JET.

A case of syndromic congenital hypothyroidism with a 15.2 Mb interstitial deletion on 2q12.3q14.2 involving &lt;i&gt;PAX8&lt;/i&gt;

Paired box 8 (PAX8) mutations are an established genetic cause of congenital hypothyroidism (CH). The majority of these mutations are found in the protein-coding exons of the gene. The proband, a 3-yr-old girl, had tetralogy of Fallot and polydactyly soon after birth. She was diagnosed with CH in the newborn screening for CH. She had a high serum TSH level (239 mU/L) and low free T4 level (0.7 ng/dL). Ultrasonography revealed thyroid hypoplasia. We performed array comparative genomic hybridization because the patient exhibited a variety of symptoms across multiple organ systems. The analysis revealed a novel heterozygous deletion that spanned a 15.2 Mb region in 2q12.3q14.3 (GRCh37; chr2:109,568,260-124,779,449). There were 71 protein-coding genes in this region, including two genes (PAX8 and GLI2) associated with congenital endocrine disorders. The common clinical features of the two previously reported patients with a total PAX8 deletion and our case were CH, short stature and intellectual disability, but the severity of hypothyroidism and other clinical features were variable. In conclusion, we describe a syndromic CH patient with a novel 2q12.3q14.3 deletion involving PAX8. Patients with CH, whose unifying diagnosis is not obvious, could have a genomic deletion involving PAX8.