Leiomyomatosis in an Infant With a SUFU Splice Site Variant: Case Report.

Heterozygous loss-of-function variants in the suppressor of fused protein gene (SUFU) can result in Gorlin syndrome, which is characterized by an increased frequency of basal cell carcinoma, medulloblastoma, odontogenic keratocysts, as well as other tumors. We describe a case of a 5-month-old female who presented with multiple intra-abdominal leiomyomata and was found to have a likely pathogenic splice site variant in the SUFU gene. This is the first reported case of leiomyomatosis secondary to a pathogenic SUFU variant in an infant and may represent an early, atypical presentation of Gorlin syndrome.

Pediatric and Young Adult Vulvovaginal Graft-versus-Host Disease.

Vulvovaginal graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication of hematopoietic stem cell transplantation (HSCT). Previous studies have reported findings restricted to predominantly adult populations. We report a case series of pediatric and young adult vulvovaginal GVHD, which was identified in 19 patients (median age, 11.8 years; range, 2.4 to 21.9 years) out of a total 302 female patients who underwent transplantation over an 8-year period at a pediatric HSCT center. The majority of patients had concomitant nongenital GVHD; only 1 patient had isolated vulvovaginal GVHD. The median time from bone marrow transplantation to diagnosis of vulvovaginal GVHD was 30 months (range, 2.3 to 97.5 months). A high percentage of the patients in our series were without vulvar or vaginal symptoms (n = 8; 42%), even though 17 patients (89%) presented with grade 3 disease based on current adult grading scales. Vulvar examination findings most frequently included interlabial and clitoral hood adhesions (89%), loss of architecture of the labia minora or clitoral hood (42%), and skin erosions or fissures (37%). Only 5 patients underwent a speculum exam, none of whom had vaginal GVHD. Examination findings of primary ovarian insufficiency (POI) can overlap with those of GVHD, and 6 patients (32%) in our cohort were diagnosed with POI. Only 1 patient was on systemic hormone replacement therapy at the time of vulvovaginal GVHD diagnosis. The majority of patients (n = 16) were treated with topical steroid therapy, with a median time to response of 43 days. Five patients (26%) had a complete response to therapy, and 10 patients (53%) had a partial response. This case series provides valuable insight into pediatric and young adult vulvovaginal GVHD and highlights the need for increased screening for vulvar disease in this population.

Pediatric and Adolescent Gynecologic Emergencies.

Diagnosis of gynecologic emergencies in the pediatric and adolescent population requires a high index of suspicion to avoid delayed or incorrect diagnoses. This article aims to dispel common misunderstandings and aid with diagnosis and management of 3 common pediatric and adolescent gynecologic emergencies: adnexal torsion, vulvovaginal lacerations, and nonsexually acquired genital ulcers.

Risk factors for atherosclerosis and the development of preatherosclerotic intimal hyperplasia.

BACKGROUND: Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of preatherosclerotic intimal hyperplasia, we correlated traditional risk factors for atherosclerosis with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. METHODS: Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of preatherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. RESULTS: Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<.0001), age 51-75 years (P=.0012), smoking (P=.008), and hypertension (P=.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51-75 years (P=.006) and smoking (P=.028) were found to be significantly associated with preatherosclerotic intimal thickening. CONCLUSIONS: In the atherosclerosis-resistant internal thoracic artery, preatherosclerotic intimal hyperplasia routinely forms during adulthood after the fourth decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis and that its formation may be influenced by traditional risk factors for atherosclerosis.

Regulation of protein kinase CK1alphaLS by dephosphorylation in response to hydrogen peroxide.

Low levels of hydrogen peroxide (H(2)O(2)) are mitogenic to mammalian cells and stimulate the hyperphosphorylation of heterogeneous nuclear ribonucleoprotein C (hnRNP-C) by protein kinase CK1alpha. However, the mechanisms by which CK1alpha is regulated have been unclear. Here it is demonstrated that low levels of H(2)O(2) stimulate the rapid dephosphorylation of CK1alphaLS, a nuclear splice form of CK1alpha. Furthermore, it is demonstrated that either treatment of endothelial cells with H(2)O(2), or dephosphorylation of CK1alphaLS in vitro enhances the association of CK1alphaLS with hnRNP-C. In addition, dephosphorylation of CK1alphaLS in vitro enhances the kinase's ability to phosphorylate hnRNP-C. While CK1alpha appears to be present in all metazoans, analysis of CK1alpha genomic sequences from several species reveals that the alternatively spliced nuclear localizing L-insert is unique to vertebrates, as is the case for hnRNP-C. These observations indicate that CK1alphaLS and hnRNP-C represent conserved components of a vertebrate-specific H(2)O(2)-responsive nuclear signaling pathway.