Juvenile xanthogranuloma in Noonan syndrome.

Noonan syndrome (NS) is one of the common RASopathies. While the clinical phenotype in NS is variable, it is typically characterized by distinctive craniofacial features, cardiac defects, reduced growth, bleeding disorders, learning issues, and an increased risk of cancer. Several different genes cause NS, all of which are involved in the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. Juvenile xanthogranuloma (JXG) is an uncommon, proliferative, self-limited cutaneous disorder that affects young individuals and may be overlooked or misdiagnosed due to its transient nature. A RASopathy that is known to be associated with JXG is neurofibromatosis type 1 (NF1). JXG in NF1 has also been reported in association with a juvenile myelomonocytic leukemia (JMML). As RASopathies, both NS and NF1 have an increased incidence of JMML. We report a 10-month-old female with NS who has a PTPN11 pathogenic variant resulting in a heterozygous SHP2 p.Y62D missense mutation. She was found to have numerous, small, yellow-pink smooth papules that were histopathologically confirmed to be JXG. In understanding the common underlying pathogenetic dysregulation of the Ras/MAPK pathway in both NS and NF1, this report suggests a possible molecular association for why NS individuals may be predisposed to JXG.

Testing for Noonan syndrome after increased nuchal translucency.

OBJECTIVE: The aim of this study was to report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. METHODS: This is a retrospective chart review. INCLUSION CRITERIA: (1) first trimester NT measurement ≥3 mm, (2) normal karyotype by either a CVS or an amniocentesis procedure, and (3) prenatal molecular genetic testing for NS completed. Results with known pathogenic variants were considered positive, while those with variants of unknown clinical significance, or with no variants, were considered negative. RESULTS: A total of 804 fetuses had an NT measurement of ≥3 mm, with a median NT thickness of 3.6 mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0 mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3 mm were not tested for NS (p = 0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. CONCLUSION: In euploid fetuses, increased NT is associated with a 10% risk of NS. © 2017 John Wiley & Sons, Ltd.

Third trimester insulin levels are not correlated with fetal macrosomia or delivery complications.

OBJECTIVE: To examine the relationship of glucose and insulin levels during the 1-hour gestational diabetes screening test to determine their relation to gestational diabetes mellitus (GDM) and possible resulting pregnancy complications. STUDY DESIGN: This is a prospective observational study of the delivery records of 784 patients who obtained third trimester screening for both glucose and insulin levels during routine 1-hour 50 g oral glucose load. RESULTS: Insulin levels were positively correlated with glucose levels (p < 0.001). GDM was diagnosed in 17 patients (2.2%). Mean birth weight was not significantly different with glucose levels < 130 pmol/L, 130-140 pmol/L, or > 140 pmol/L (3,282 g, 3,409 g, and 3,310 g, respectively, p = 0.13), nor were 5-minute Apgar scores (p = 0.66). No difference in mean fetal birth weight was found in insulin ranges < 30 pmol/L, 30-60 pmol/L, and > 60 pmol/L (3,330 g, 3,306 g, and 3,276 g, respectively, p = 0.56). Moreover, no significant differences in 5-minute Apgar scores were observed between those groups (p = 0.05). Women who underwent cesarean section (n = 230) had significantly higher glucose and insulin levels than did those who had vaginal deliveries (n = 554) (p = 0.01 and p = 0.003, respectively). CONCLUSION: Our data indicates that neither insulin nor glucose levels are predictive of fetal macrosomia, low Apgar scores, or birth injuries.

Low-intensity shockwave therapy improves baseline erectile function: a randomized sham-controlled crossover trial.

Background: Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option. Aim: This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction. Methods: Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month. Outcomes: Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy. Results: At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs -0.7, P = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline (P < .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score <3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment. Clinical Implications: In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy. Strengths and Limitations: Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution. Conclusions: Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment. Clinical Trial Registration: ClinicalTrials.gov NCT04434352.