Goldenhar syndrome with limbal neoformation, microtia and skeletal deformities: a case report and literature review.

BACKGROUND: To report a case of a 4-year-old patient with Goldenhar syndrome. CASE PRESENTATION: The author presents a rare case report involving a 4-year-old boy with multiple malformations. A comprehensive examination showed that the patient primarily had a limbal dermoid. He also has bilateral microtia and ear canal deformities. The skull CT scan and spine X-ray showed Maxillofacial Abnormalities and scoliosis. Whole Exome Sequencing revealed potential gene variations related to microtia. Although certain circumstances prevented us from initiating follow-up treatment for the patient, we have provided a detailed account of the diagnostic methodologies used for this condition. CONCLUSIONS: Goldenhar syndrome is a congenital condition, predominantly presenting as sporadic cases. Its diagnosis and management typically necessitate the involvement of multiple disciplines, including otolaryngology and craniofacial surgery. The syndrome encompasses a variety of craniofacial features, which can facilitate early diagnosis and guide subsequent therapeutic interventions.

Local injection of abaloparatide promotes mandibular condyle lengthening in adolescent rats via enhancing chondrogenesis and ossification.

BACKGROUND: Mandibular condylar hypoplasia negatively affects patient's facial appearance and dentofacial function. OBJECTIVE: To investigate the effect of local injection of the drug abaloparatide (ABL), an analogue of parathyroid hormone related protein (PTHrP), on promoting lengthening of the mandibular condyle. METHODS: Thirty adolescent male Sprague-Dawley rats were randomly divided into two groups, which received the injection of ABL or normal saline (the control) every 3 days in the temporomandibular joint (TMJ) cavity. Cone-beam computed tomography and immunohistochemistry assays were performed at 2, 4 and 6 weeks since the injection. Mandibular condylar chondrocytes (MCC) and pre-osteoblasts were treated with ABL or PBS, followed by the CCK-8 detection, IC50, real-time PCR assay, Western Blot and immunofluorescence staining. RESULTS: In vivo, compared with the control, the ABL group significantly increased the mandibular condylar process length (by 1.34 ± 0.59 mm at 6 weeks), the thickness of the cartilage layer, and enhanced the matrix synthesis. The ABL group had significant up-regulation of SOX 9, COL II, PTHrP and PTH1R, down-regulation of COL X in the cartilage, up-regulation of RUNX 2, and unchanged osteoclastogenesis in the subchondral bone. In vitro, the intra-TMJ injection of ABL promoted the MCC proliferation, with up-regulated expression of chondrogenic genes, and enhanced osteogenic differentiation of the pre-osteoblasts. CONCLUSIONS: Intra-TMJ injection of abaloparatide promotes mandibular condyle lengthening in the adolescent rats via enhancing chondrogenesis in the mandibular condylar cartilage and ossification in the subchondral bone.

Mandibular stability and condylar changes following orthognathic surgery in mandibular hypoplasia patients associated with preoperative condylar resorption.

OBJECTIVES: To evaluate postoperative mandibular stability and condylar changes in patients with mandibular hypoplasia and preoperative condylar resorption (CR) undergoing orthognathic surgery. MATERIALS AND METHODS: Fifty-four patients were included in this retrospective study. Computed tomography (CT) scans were acquired preoperatively (T0), 2-7 days immediate postoperatively (T1), and at least 1 year postoperatively (T2). Three-dimensional (3D) cephalometric analysis and measurements of condylar angle, volume, and position (joint spaces) were performed. A 2-mm mandibular relapse was deemed clinically acceptable. We also analyzed the correlations between relapse and postoperative CR and susceptible factors using a multivariate logistic regression model. RESULTS: The results showed one year after the surgery, the average mandibular relapse was 1.0 mm (p < 0.05), and the average reduction of condylar volume was 152.4 mm3 (12.7%). Condyle-fossa relationships were improved immediately after the surgery, with a tendency of returning to their original state in the follow-up (p < 0.05). Anteroposterior advancement at point B (B-CP advancement) at T1 and superior joint space (SJS) at T0 were significantly correlated with mandibular relapse, and postoperative CR was mainly associated with vertical increasement at point B (B-AP increasement) at T1. The optimal cut-off values were as follows: 1.6 mm for SJS, 4.2 mm for B-CP advancement, and 1.8 mm for B-AP increasement. Concomitant advancement Genioplasty showed no significant correlation with relapse and postoperative CR. CONCLUSIONS: While patients with mandibular hypoplasia and preoperative CR were vulnerable to further condylar resorption after mandibular advancement, the treatment outcomes were generally clinically acceptable. Postoperative relapse was associated with a larger than 4.2 mm of mandibular advancement measured at B-CP and a larger than 1.6 mm of superior joint space measured at SJS, and postoperative CR was associated with a larger than 1.8 mm of mandibular vertical increasement measured at B-AP. CLINICAL RELEVANCE: The findings of this study suggested that the mandibular advancement might be limited to 5 mm for patients with preoperative CR. A concomitant advancement genioplasty might also be considered to achieve a better facial profile in these patients.

Osteogenesis Modulation: Induction of Mandibular Bone Growth in Adults by Electrical Field for Aesthetic Purposes.

BACKGROUND: A new technique in plastic surgery termed Osteogenesis Modulation is described. This technique uses a surgically implanted, battery-operated medical device to deliver customized electrical pulses to produce mandibular bone growth. This device was designed to be a temporary, nonpermanent implant. The purpose of this study was to review both the safety and efficacy of Osteogenesis Modulation. METHODS: This study comprises two phases. Phase I involved experimental technology development and animal experiments. Phase II included technology development for clinical use and a clinical trial. In Phase II, four patients with a diagnosis of mandibular hypoplasia and microgenia underwent surgical implantation of the novel medical device over the chin bone. Once a satisfactory change of contour of mandibular bone was achieved, the devices were removed. In all patients, the devices were left in place for 12 months, then surgically removed under local anesthesia. Preoperative and long-term postoperative cephalometric controls were done. RESULTS: In all patients, symmetrical mandibular bone growth was observed with good-to-excellent aesthetic results. The overall follow-up period was 39 months. Cephalometric controls taken 3 to 6 months after the device removal showed an average increase in mandible length of 5.26mm (range, 2.83-7.60mm) CONCLUSIONS: Preliminary clinical results suggest that Osteogenesis Modulation is a safe, minimally invasive, and effective alternative treatment for the correction of mandibular hypoplasia in selected cases. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice.

OBJECTIVE: Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. MATERIALS AND METHODS: Dmp1Cre ;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre ;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. RESULTS: Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre ;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. CONCLUSIONS: Augmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.

Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.

Characterization of the perinatal mandible growth pattern: preliminary results.

PURPOSE: The fetal development of the mandible is nowadays quite understood, and it is already known that craniofacial growth reaches its highest rate during the first 5 years of postnatal life. However, there are very few data focusing on the perinatal period. Thus, the present article is addressing this concern by studying the mandible morphology and its evolution around the birth with a morphometric method. METHODS: Thirty-one mandibles modelled in three dimensions from post-mortem CT-scans were analyzed. This sample was divided into two subgroups composed of, respectively, 15 fetuses (aged from 36 gestational weeks), and 16 infants (aged to 12 postnatal weeks). 17 distances, 3 angles, and 8 thicknesses were measured via the prior set of 14 landmarks, illustrating the whole mandible morphology. RESULTS: Although this methodology may depend on the image reconstruction quality, its reliability was demonstrated with low variability in the results. It highlighted two distinct growth patterns around birth: fetuses mandibles do not significantly evolve during the perinatal period, whereas, from the second postnatal weeks, most of the measurements increased in a homogeneous tendency and in correlation with age. CONCLUSIONS: The protocol developed in this study highlighted the morphologic evolution of the mandible around birth, identifying a different growth pattern from 2 postnatal weeks, probably because of the progressive activation of masticatory muscles and tongue. However, considering the small sample size, these results should be thorough, so identification and management of anatomic abnormalities could eventually be achieved.

Maxillofacial features and systemic malformations in expanded spectrum Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare, multisystemic congenital disease with estimated frequency of 1/26370 births in Europe. Most cases are sporadic and caused by unilateral abnormal morphogenesis of the first and second pharyngeal arches. The aim of this study is to define the types and frequency of maxillofacial and systemic malformations in HFM patients. This is a case series study of patients with HFM evaluated at a single institution. Data were acquired through history, physical examination, photographs, diagnostic radiology, and laboratory and analyzed by the FileMakerPro database on 95 patients (54F; 41M) of which 89 met the inclusion criteria. Mandibular hypoplasia was observed in 86 patients with right-side preponderance (50). One patient had bilateral mandibular hypoplasia. Seventy-four had external ear anomalies (anotia or microtia). Eleven had bilateral malformed ears. Hearing impairment, associated with stenosis or atresia of the external ear canal, was found in 69 patients (eight with bilateral canal defects). Ocular anomalies were seen in 41 (23 with dermoid cysts) and 39 had orbital malformations. Facial nerve paralysis was observed in 38 patients. Cleft lip/palate (10), preauricular tags (55), and macrostomia (41) were also described. A total of 73/86 had systemic malformations, mainly vertebral (40), genitourinary (25), and cardiovascular (28). Sixteen had cerebral anomalies (four with intellectual disability). All patients suspected of HFM should undergo a complete systematic clinical and imaging investigation to define the full scope of anomalies. Since the disease is rare and complex, affected patients should be monitored by specialized multidisciplinary team centers.

Analysis of the Relationship Between Micrognathia and Cleft Palate: A Systematic Review.

Objective To gather data from relevant experimental and observational studies to determine the relationship between micrognathia and cleft palate. The goal is to raise awareness and motivate clinicians to consider the cause and effect relationship when confronted with patients with cleft palate, even if there is no clearly noticeable mandibular abnormality. Design Several electronic databases were systematically examined to find articles for this review, using search terms including "cleft palate," "micrognathia," "tongue," and "airway obstruction." PubMed was the source of all the articles chosen to be included. Exclusion criteria included case reports, articles focused on treatment options, and articles only tangentially related to cleft palate and/or micrognathia. Results A total of 930 articles were screened for relevance, and 82 articles were chosen for further analysis. Evidence gathered in this review includes a variety of etiological factors that are causative or associated with both micrognathia and cleft palate. Observational studies relating the two abnormalities are also included. Much of the included literature recognizes a cause-and-effect relationship between micrognathia and cleft palate. Conclusion On the basis of the published data, we suggest that micrognathia does induce cleft palate in humans and animals. With knowledge of this causative relationship, clinicians should consider the importance of gathering cephalometric data on the mandibles and tongues of patients presenting with isolated cleft palate to determine whether they have micrognathia as well. With more data, patterns may emerge that could give insight into the complex etiology of nonsyndromic cleft palate.

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome.

Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.

Anesthetic management of a patient with mandibular hypoplasia, deafness, progeroid features, lipodystrophy syndrome: a case report.

BACKGROUND: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder that presents unique challenges for anesthetic management due to its multisystemic manifestations. This report outlines the anesthetic considerations for MDPL patients based on our case experience. CASE PRESENTATION: A 15-year-old male with MDPL syndrome underwent testicular extraction under general anesthesia. Insertion of a peripheral venous catheter was challenging due to scleroderma-like skin. Although the facial features of MDPL syndrome suggested a difficult airway, intubation with a McGrath™ Mac video laryngoscope was successful. Despite MDPL syndrome's association with hypertriglyceridemia due to lipodystrophy, this patient's triglyceride levels were normal. Thiamylal and sevoflurane were used without issues such as delayed emergence from anesthesia. CONCLUSIONS: MDPL syndrome requires careful preoperative assessment and tailored anesthetic management due to potential airway challenges arising from its distinctive facial features and the possibility of altered anesthetic pharmacokinetics associated with lipodystrophy.

Complexities of Hemifacial Microsomia: A Case Study of Mandibular Hypoplasia and Ear Deformity.

Hemifacial microsomia (HFM) presents a complex congenital anomaly characterized by the asymmetric underdevelopment of facial structures, predominantly affecting the ear, mouth, and mandible on one side of the face. This case study examines the intricacies of HFM through the presentation of a 23-year-old female with congenital deformities of the left ear and mandibular hypoplasia. Clinical and radiological evaluations revealed significant facial malformations, including mandibular hypoplasia, left temporomandibular joint fusion, and maxillary abnormalities, confirming the diagnosis of HFM. Management of HFM necessitates a multidisciplinary approach involving otolaryngologists, maxillofacial surgeons, orthodontists, and audiologists to comprehensively address functional and aesthetic concerns. Early diagnosis and intervention, along with psychosocial support, are essential for optimizing outcomes and improving the quality of life for individuals with HFM.

Case report: A novel splice-site mutation of MTX2 gene caused mandibuloacral dysplasia progeroid syndrome: the first report from China and literature review.

Background: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported. Methods: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date. Results: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades. Conclusion: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

Congenital Mandibular Hypoplasia: Patient-Specific Total Joint Replacement as a Line Extension in the Treatment of Complex Craniofacial Anomalies.

Introduction: Congenital mandibular hypoplasia (CMH) remains challenging because of the underlying combined hard and soft tissue deficiency. Treatment options include craniofacial distraction, orthognathic surgery, and autologous grafts, although the latter produces inadequate results after distraction and autologous grafting. Unsatisfactory long-term stability may cause relapse, necessitating reoperation. Material and Methods: We investigated the feasibility of using alloplastic total joint replacement (TJR) in growing and young adult CMH patients. The primary outcome was long-term reconstruction stability, without implant failure. Secondary outcomes were TMJ function and pain, and jaw movements achieved during surgery. Results: Three patients (age: 9-22 years) were treated by the same surgeon at one institution during 2018-2021. Anamnesis and clinical parameters were obtained from patient records. Preoperative 3D-scans were superimposed with postoperative 3D-scans and preoperative plans, including TJR-implant STL files, to measure jaw movement. All patients underwent prior reconstructive surgery. Mandibular movement of 16.4-20.1 mm in the sagittal direction was achieved. Post-TJR follow-up ranged from 24 to 42 months. No long-term complications occurred. At the latest follow-up, the maximal interincisal opening was between 21 and 40 mm, and all implants were functioning, without failure. Conclusion: In selected CMH cases, alloplastic TJR can deliver satisfactory medium-term results with predictable and stable outcomes, even in growing patients.

Early Outcomes and Risk Factors in Orthognathic Surgery for Mandibular and Maxillary Hypo- and Hyperplasia: A 13-Year Analysis of a Multi-Institutional Database.

BACKGROUND: Orthognathic surgery (OS) is a frequently performed procedure for the correction of dentofacial deformities and malocclusion. Research on OS is mostly limited to single-surgeon experience or single-institutional reports. We, therefore, retrospectively analyzed a multi-institutional database to investigate outcomes of OS and identify risk factors for peri- and postoperative complications. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2020) to identify patients who underwent OS for mandibular and maxillary hypo- and hyperplasia. The postoperative outcomes of interest included 30-day surgical and medical complications, reoperation, readmission, and mortality. We also evaluated risk factors for complications. RESULTS: The study population included 674 patients, 48% of whom underwent single jaw surgery, 40% double jaw surgery, and 5.5% triple jaw surgery. The average age was 29 ± 11 years, with an equal gender distribution (females: n = 336; 50%, males: n = 338; 50%). Adverse events were relatively rare, with a total of 29 (4.3%) complications reported. The most common surgical complication was superficial incisional infection (n = 14; 2.1%). While the multivariable analysis revealed isolated single lower jaw surgery (p = 0.03) to be independently associated with surgical complication occurrence, it also identified an association between the outpatient setting and the frequency of surgical complications (p = 0.03) and readmissions (p = 0.02). In addition, Asian ethnicity was identified as a risk factor for bleeding (p = 0.003) and readmission (p = 0.0009). CONCLUSION: Based on the information recorded by the ACS-NSQIP database, our analysis underscored the positive (short-term) safety profile of OS. We found OS of the mandible to be associated with higher complication rates. The calculated risk role of OS in the outpatient setting warrants further investigation. A significant correlation between Asian OS patients and postoperative adverse events was found. Implementation of these novel risk factors into the surgical workflow may help facial surgeons refine their patient selection and improve patient outcomes. Future studies are needed to investigate the causal relationships of the observed statistical correlations.

Orthodontic-surgical treatment of an Angle Class II malocclusion patient with mandibular hypoplasia and missing maxillary first molars: A case report.

BACKGROUND: Adult patients presenting with Angle Class II division 1 malocclusions that have a strong skeletal etiology can be challenging for clinicians, particularly if accompanied by retrognathia of the mandible and a dolichofacial growth pattern. CASE SUMMARY: In this case report, we describe the successful orthodontic and surgical management of a 20-year-old woman with an Angle Class II malocclusion with a severe anteroposterior skeletal discrepancy characterized by mandibular deficiency. She had incompetent lips, dental and skeletal Class II malocclusion, high mandibular plane angle, mild mandibular crowding, and two missing maxillary first molars. The treatment plan comprised: (1) Extraction of two mandibular second premolars to decompensate and retract mandibular incisors; (2) pre-surgical alignment, leveling, and space closure of the teeth in both arches, and protraction of the second maxillary molars to close the maxillary space; (3) surgical treatment including a LeFort I osteotomy for maxillary retraction and rotation, a bilateral sagittal split osteotomy for mandibular advancement and rotation, and a genioplasty for correctting the skeletal deformities; and (4) post-surgical correction of the malocclusion. CONCLUSION: The patient's facial esthetics was significantly improved and a desirable occlusion was achieved after 16 mo treatment. Follow-up records after 2 years showed stable esthetics and function.

A Possible Incomplete Form of Treacher Collins Syndrome: A Case Report.

Treacher Collins syndrome (TCS) is a rare genetic disorder that affects craniofacial development due to malformation of the first and second branchial arches. The TCOF1 gene is mainly responsible for this condition. Here, we present a case of a 13-year-old adolescent girl with complaints of maligned teeth with conductive deafness. On clinical examination, she had retrognathia, a broad nose, maligned teeth, a high arch palate, and midfacial hypoplasia. On the basis of the clinical findings, a diagnosis of a mild-variant TCS was made as eyes were not involved and supportive treatment was given to the patient. The symptoms of the disease have a varying range of severity. Early diagnosis and supportive treatments, which include multidisciplinary treatment involving pediatrics, otolaryngologists, audiologists, orthodontists, and psychologists, are very important for the management of such cases.

A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient.

BACKGROUND: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient. METHODS: We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing. Additionally, the literature concerning MDPL was reviewed to do a retrospective analysis of the pathogenesis, genotype-phenotype correlation, and clinical management. RESULTS: The proband was diagnosed with MDPL, presenting with mandibular hypoplasia, a characteristic facial appearance, lipodystrophy, and sensorineural hearing loss (SNHL). Whole-exome sequencing and bioinformatics analysis revealed a de novo missense variant in the POLD1 gene, NM_002691.4:c.3185A>G (NP_002682.2:p.(Gln1062Arg)). The retrospective analysis showed wide variation in the MDPL phenotype, but the most frequent features included mandibular hypoplasia, characteristic facial appearance, lipodystrophy, and SNHL. CONCLUSIONS: This study supplements the mutational spectrum of POLD1. The genetic analysis contributes to the diagnosis of syndromic deafness, and it has a vital role in clinical management and future genetic consultation.

Orthopaedic Aspects of SAMS Syndrome.

The combination of short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS, OMIM: 602471) has been reported as an ultra-rare, autosomal-recessive developmental disorder with unique skeletal anomalies. To the present date, only four affected individuals have been reported. There are several striking orthopaedic diagnoses within the SAMS syndrome. In particular, the scapulohumoral synostosis and the bilateral congenital ventral dislocation of the hips. The purpose of this report is to underline the importance of recognizing pathognomic features of SAMS syndrome. Whenever a bilateral congenital ventral dislocation of the hips and/or a scapulohumoral synostosis is found or clinically suspected, SAMS syndrome should be considered as the primary diagnosis until proven otherwise.