A Simple Clinical Application for Locating the Frontotemporal Branch of the Facial Nerve Using the Zygomatic Arch and the Tragus.

BACKGROUND: The seventh cranial nerve (CN VII), also known as the facial nerve, is an anatomically intricate structure the branches of which serve several physiologic functions. CN VII innervates the muscles of facial expression which are crucial for eye protection, oral competence, and social interaction. The temporal branch, clinically referred to as the frontotemporal branch (FTB), is the most superior of the 5 branches and is at risk during cutaneous surgery of the parotid gland and in the temporal region. Several methods for delineating the FTB trajectory exist, the most widely known being Pitanguy's Line, which is defined as running from 0.5 cm below the tragus to 1.5 cm above the lateral eyebrow. However, variations in eyebrow location, often affected by modern-day cosmetic trends, complicate the accuracy of this approach. OBJECTIVES: The aim of this study was to develop a surgical landmark to identify FTB location without relying on soft tissue structures. METHODS: To minimize variation, we chose landmarks that were both consistent and easy to locate based on simple surface anatomy. Twenty-one cadaver hemifaces were dissected in order to locate the FTB in relation to the inferior border of the zygomatic arch and the apex of the tragus. RESULTS: We found that the mean ± SEM distance from the apex of the tragus to the point where the FTB crossed the inferior border of the zygomatic arch was 3.21 ± 0.05 cm. CONCLUSIONS: Through the use of this measurement, we aim to avoid the pitfalls of previous techniques by providing a widely applicable clinical tool based on landmarks easily found on any patient.

Phenotype Driven Analysis of Whole Genome Sequencing Identifies Deep Intronic Variants that Cause Retinal Dystrophies by Aberrant Exonization.

Purpose: To demonstrate the effectiveness of combining retinal phenotyping and focused variant filtering from genome sequencing (GS) in identifying deep intronic disease causing variants in inherited retinal dystrophies. Methods: Affected members from three pedigrees with classical enhanced S-cone syndrome (ESCS; Pedigree 1), congenital stationary night blindness (CSNB; Pedigree 2), and achromatopsia (ACHM; Pedigree 3), respectively, underwent detailed ophthalmologic evaluation, optical coherence tomography, and electroretinography. The probands underwent panel-based genetic testing followed by GS analysis. Minigene constructs (NR2E3, GPR179 and CNGB3) and patient-derived cDNA experiments (NR2E3 and GPR179) were performed to assess the functional effect of the deep intronic variants. Results: The electrophysiological findings confirmed the clinical diagnosis of ESCS, CSNB, and ACHM in the respective pedigrees. Panel-based testing revealed heterozygous pathogenic variants in NR2E3 (NM_014249.3; c.119-2A>C; Pedigree 1) and CNGB3 (NM_019098.4; c.1148delC/p.Thr383Ilefs*13; Pedigree 3). The GS revealed heterozygous deep intronic variants in Pedigrees 1 (NR2E3; c.1100+1124G>A) and 3 (CNGB3; c.852+4751A>T), and a homozygous GPR179 variant in Pedigree 2 (NM_001004334.3; c.903+343G>A). The identified variants segregated with the phenotype in all pedigrees. All deep intronic variants were predicted to generate a splice acceptor gain causing aberrant exonization in NR2E3 [89 base pairs (bp)], GPR179 (197 bp), and CNGB3 (73 bp); splicing defects were validated through patient-derived cDNA experiments and/or minigene constructs and rescued by antisense oligonucleotide treatment. Conclusions: Deep intronic mutations contribute to missing heritability in retinal dystrophies. Combining results from phenotype-directed gene panel testing, GS, and in silico splice prediction tools can help identify these difficult-to-detect pathogenic deep intronic variants.