Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family of signaling molecules. ERK is predominantly found in two forms, ERK1 (p44) and ERK2 (p42), respectively. There are also several atypical forms of ERK, including ERK3, ERK4, ERK5 and ERK7. The ERK1/2 signaling pathway has been implicated in many and diverse cellular events, including proliferation, growth, differentiation, cell migration, cell survival, metabolism and transcription. ERK1/2 is activated (i.e., phosphorylated) in the cytosol and subsequently translocated to the nucleus, where it activates transcription factors including, but not limited to, ETS, c-Jun, and Fos. It is not surprising that the ERK1/2 signaling cascade has been implicated in many pathological conditions, namely, cancer, arthritis, chronic inflammation, and osteoporosis. This narrative review examines many of the cellular events in which the ERK1/2 signaling cascade plays a critical role. It is anticipated that agents designed to inhibit ERK1/2 activation or p-ERK1/2 activity will be developed for the treatment of those diseases characterized by dysregulated gene expression through ERK1/2 activation.

Pyriform aperture stenosis (PAS) and choanal atresia (CA) are 2 anatomic causes of newborn nasal obstruction. The goal of management of PAS and CA is to establish a patent nasal airway, often requiring surgery. No previous study has sought to assess the long term sinonasal and otologic disease incidence and outcomes in the PAS and CA population after surgical intervention. The goal of this study was to investigate whether surgical intervention in PAS and CA is correlated with the long-term development of sinonasal disease or otologic disease (either recurrent acute otitis media or chronic otitis media with effusion). Patients with a diagnosis of PAS or CA who underwent surgical intervention were retrospectively identified. Pertinent demographic risk factors, medical and syndromic diagnoses, number of surgical interventions, types of surgical interventions, and presence of sinonasal and otologic diseases were assessed. Fifty-three patients were included in the study: 8 patients with PAS and 45 with CA. The average followup time was 2.9 years. No PAS patients developed otologic or sino-nasal disease. Four of 45 patients with CA developed recurrent acute sinusitis (3 non-syndromic and 1 syndromic) and 19 of 45 patients developed otologic disease (9 non-syndromic and 10 syndromic). Coloboma, Heart, Choanal Atresia, Growth Retardation, Genitourinary, Ear Syndrome and unilateral CA correlated significantly with the subsequent development of otologic disease; however, the number of surgeries did not. This study suggests that surgery for PAS and CA do not increase the risk of long-term development of sinonasal or otologic disease.

ObjectiveInvestigate incidence and natural history of otologic and sinonasal disease associated with 22q11.2 deletion syndrome.Study DesignCase series.SettingTertiary care children's hospital.MethodsCharts from consecutive children born 2000 to 2018 with a diagnosis of 22q11.2 deletion, DiGeorge, or velocardiofacial syndrome based on the International Classification of Diseases (ICD)‐9 and ICD‐10 codes were reviewed. Otologic and rhinologic diagnoses and surgeries and immune and microbiologic laboratory findings were collected from the medical record.ResultsAfter the exclusion of patients with no 22q11.2 deletion (n = 101), otologic care at an outside hospital (n = 59), and loss to follow‐up prior to 3 years of age (n = 22), 128 were included. Males comprised 80 (62.5%) patients, 115 (89.8%) were white, and the median age at genetic confirmation of 22q11.2 deletion was 119 days (range 0 days to 14.6 years). Recurrent acute otitis media (RAOM), chronic otitis media with effusion, chronic rhinosinusitis, and recurrent acute sinusitis were diagnosed in 54 (42.2%), 37 (28.9%), 10 (7.8%), and 8 (6.3%), respectively. Tympanostomy tubes were placed in 49 (38.3%). Adenoidectomy and sinus surgery were performed in 38 (29.7%) and 4 (3.1%), respectively. Neither immunoglobulin nor cluster of differentiation deficiency increased the odds of RAOM diagnosis, tympanostomy tube placement, or chronic/recurrent sinusitis. Methicillin‐resistant Staphylococcus aureus was the most common organism in sinus cultures (4/13, 30.8%). Streptococcus pneumonia dominated otorrhea cultures (11/21, 52.4%).ConclusionApproximately half of children with 22q11.2 deletion may experience otologic disease that often requires surgical management. Future studies will utilize a larger cohort to examine the role of immunodeficiency in otologic and rhinologic disease in this population.