Compound heterozygosity for loss-of-function GARS variants results in a multisystem developmental syndrome that includes severe growth retardation.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes that ligate amino acids onto tRNA molecules. Genes encoding ARSs have been implicated in myriad dominant and recessive disease phenotypes. Glycyl-tRNA synthetase (GARS) is a bifunctional ARS that charges tRNAGly in the cytoplasm and mitochondria. GARS variants have been associated with dominant Charcot-Marie-Tooth disease but have not been convincingly implicated in recessive phenotypes. Here, we describe a patient from the NIH Undiagnosed Diseases Program with a multisystem, developmental phenotype. Whole-exome sequence analysis revealed that the patient is compound heterozygous for one frameshift (p.Glu83Ilefs*6) and one missense (p.Arg310Gln) GARS variant. Using in vitro and in vivo functional studies, we show that both GARS variants cause a loss-of-function effect: the frameshift variant results in depleted protein levels and the missense variant reduces GARS tRNA charging activity. In support of GARS variant pathogenicity, our patient shows striking phenotypic overlap with other patients having ARS-related recessive diseases, including features associated with variants in both cytoplasmic and mitochondrial ARSs; this observation is consistent with the essential function of GARS in both cellular locations. In summary, our clinical, genetic, and functional analyses expand the phenotypic spectrum associated with GARS variants.

An Update on Diagnosis and Pharmacologic Therapy for Headache in the Oral and Maxillofacial Surgery Practice.

Headaches are synonymous with neurovascular pain (cephalalgias), which comprise a heterogeneous group of pain disorders that share a common anatomic region (head and neck). Headaches are often a "universal" disease presentation that is evaluated by the oral and maxillofacial surgeon. Pharmacologic therapy of headaches is most often based on the severity of symptoms and the degree of disability experienced by the patient. This article describes the epidemiology of neurovascular headaches, their pathophysiologic mechanisms/presentation, the workup of patients, and an up-to-date overview of pharmacologic approaches that can be applied in the oral and maxillofacial surgical practice to treat this patient population.

Surgical Reduction of Chronic Bilateral Traumatic Dislocation of the Mandibular Condyles With Erosion of the Middle Fossa Floor: Case Report With Surgical Video.

BACKGROUND: Dislocation of the mandibular condyle (MC) is not a common condition, but when a traumatic case involves erosion of the middle fossa floor, it becomes a much more complicated and even rarer pathology. OBJECTIVE: To describe the management of traumatic dislocation of the MCs with erosion of the middle fossa floor. We provide a step-by-step surgical video demonstrating reestablishment of the condylar position and occlusion. METHODS: A 65-yr-old woman with rheumatoid arthritis presented after a ground-level fall. She was admitted to the intensive care unit with simultaneous complex medical conditions, intubated, and medically treated for over a month. She was seen in outpatient follow-up 2 mo later and noted to have an anterior open bite and bilateral temporomandibular joint pain. Computed tomography of the face showed bilateral dislocation of the MCs with erosion of the middle fossa floor. RESULTS: Open surgical treatment with bilateral eminectomies was performed to obtain adequate reduction, involving a multidisciplinary team including neurosurgery, oral-maxillofacial surgery, and otolaryngological surgery. She did well postoperatively. CONCLUSION: Multiple factors predispose a patient to MC dislocation, but we believe the catalyst in this case was significant manipulation of the jaw during endotracheal intubation. A chronic postoperative open bite can lead to much more difficult treatment, given bony erosion and fibrotic tissue formation. This case highlights the challenges of diagnosis and treatment of a bilateral traumatic dislocation and provides a surgical video reference description of repair and resolution.

Persistent allergic contact dermatitis to plastic toilet seats.

Allergic contact dermatitis to various components of toilet seats is being recognized and reported with increasing frequency. This report details the case of an young girl who was found to be allergic to plastic found in both a toilet seat and a school chair. It highlights particular problems with patch testing young children and the difficulty in confirming allergy to plastics.

The versatile "lip switch" or transitional flap vestibuloplasty combined with alveoloplasty and implant placement to treat atrophic mandibles with inadequate vestibules and attached tissue: A case series and review of the literature.

INTRODUCTION/AIMS: The edentulous mandibular ridge and associated shallow vestibule are often seen as a challenge in the oral rehabilitation of patients. Dental implants can provide an improvement in mastication and patient satisfaction. The aim of this study is to utilize a preprosthetic mucosal flap combined with a repositional periosteal flap concomitant with an alveoloplasty and placement of endosteal implants as a single-stage procedure in the anterior mandible. This approach provides a valued alternative for dental rehabilitation in patients with poor masticatory efficiency using a conventional denture. METHODS: Eight patients underwent the preprosthetic surgical plan in the oral surgery clinic of the dental school during a 1-year period. Age, sex, preoperative, and postoperative vestibular depth, as well as hard and soft tissue elements were measured (P < .05) at 4-6 months. RESULTS: Mean age was 53 years ± 14.62 (N = 8). Anterior mandible height was 19 ± 4.8 mm. A significant difference was measured using a two-tailed Student's t-test between pre- and postoperative vestibular depths, respectively (3.9 mm vs 10.5 ± 0.96 mm; P < .01). CONCLUSIONS: A lip switch vestibuloplasty combined with placement of two implants provide a one-stage procedure that is convenient, provides a shorter postoperative period, and can be financially affordable. Future research requires larger sampling to support this treatment as a standard of care.

Medically Complex Dental Implant Patients: Controversies About Systemic Disease and Dental Implant Success/Survival.

Advances in dental implant therapy have created choices to enhance the expectations of dental practitioners and their patients with respect to oral rehabilitation at any age after childhood and regardless of, in most cases, medical disabilities. The medical status of the patient however can significantly influence the success rate of dental implant therapy. This article applies the hierarchy of scientific evidence ranging from case reports, retrospective, prospective cohort investigations, systematic reviews, and meta-analyses criteria in order to determine whether dental implant placement in medically compromised patients yields any detrimental sequelae.

Treatment of the Dental Patient with Bleeding Dyscrasias: Etiologies and Management Options for Surgical Success in Practice.

The oral health care provider sees a significant number of patients in his or her practice who suffer from systemic diseases affecting the ability to clot. These medical issues can be acquired or inherited bleeding dyscrasias requiring pharmacologic therapy during the perioperative period. Patients with inherited or acquired bleeding disorders require careful attention with respect to the assessment of bleeding risk. This article develops algorithms to manage acquired and inherited bleeding dyscrasias. These approaches include a discussion of the epidemiology of bleeding disorders in surgical patients, mechanism of hemostasis, and strategies for patient management based on the etiology of bleeding disorder.

Deficiency in the endocytic adaptor proteins PHETA1/2 impairs renal and craniofacial development.

A critical barrier in the treatment of endosomal and lysosomal diseases is the lack of understanding of the in vivo functions of the putative causative genes. We addressed this by investigating a key pair of endocytic adaptor proteins, PH domain-containing endocytic trafficking adaptor 1 and 2 (PHETA1/2; also known as FAM109A/B, Ses1/2, IPIP27A/B), which interact with the protein product of OCRL, the causative gene for Lowe syndrome. Here, we conducted the first study of PHETA1/2 in vivo, utilizing the zebrafish system. We found that impairment of both zebrafish orthologs, pheta1 and pheta2, disrupted endocytosis and ciliogenesis in renal tissues. In addition, pheta1/2 mutant animals exhibited reduced jaw size and delayed chondrocyte differentiation, indicating a role in craniofacial development. Deficiency of pheta1/2 resulted in dysregulation of cathepsin K, which led to an increased abundance of type II collagen in craniofacial cartilages, a marker of immature cartilage extracellular matrix. Cathepsin K inhibition rescued the craniofacial phenotypes in the pheta1/2 double mutants. The abnormal renal and craniofacial phenotypes in the pheta1/2 mutant animals were consistent with the clinical presentation of a patient with a de novo arginine (R) to cysteine (C) variant (R6C) of PHETA1. Expressing the patient-specific variant in zebrafish exacerbated craniofacial deficits, suggesting that the R6C allele acts in a dominant-negative manner. Together, these results provide insights into the in vivo roles of PHETA1/2 and suggest that the R6C variant is contributory to the pathogenesis of disease in the patient.This article has an associated First Person interview with the first author of the paper.

Sterile inflammation associated with transradial catheterization and hydrophilic sheaths.

In 1999, we noted the development of inflammation and/or abscesses at the site of radial access in a group of patients. Over a 3-year period, we noted this inflammation in 33 patients out of 2,038 (1.6%) who had catheterization via the radial approach. The radial abscesses occurred in 30 patients out of 1,063 (2.8%) in whom we could confirm the use of a hydrophilic-coated sheath, but in no patient for whom we can document that an uncoated sheath was used. No infectious agent could be implicated, and the time course for the development of the abscess, typically 2 to 3 weeks, seemed long for a bacterial infection. Later patients had biopsies, and granulomatous reactions were seen in most. Additionally, a few of the biopsies showed an amorphous extravascular substance consistent with the catheter coating. All patients had good long-term outcomes.