Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis.

BACKGROUND: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODS: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTS: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONS: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).

Preference for secondary findings in prenatal and pediatric exome sequencing.

OBJECTIVE: We aimed to determine the frequency of accepting secondary findings in families undergoing exome sequencing in prenatal and pediatric settings. METHODS: This was a secondary analysis of prospectively enrolled patients undergoing trio exome sequencing for congenital anomalies or developmental disorders in prenatal and pediatric settings, in which families were offered receiving secondary findings (initially assessed in the proband and, if identified, then in the parents). The primary outcome was frequency of accepting secondary findings. Secondary outcomes included frequency of acceptance in prenatal versus pediatric settings, and sociodemographic differences between those who accepted versus declined secondary findings. RESULTS: There were 682 families included in the cohort (289 prenatal and 393 pediatric). Overall, 84% (576/682) of families accepted secondary findings: 86.2% (249/289) of families undergoing prenatal versus 83.2% (327/393) pediatric (p = 0.30) testing. Secondary findings were identified in 2.6% (15/576) of cases, with no difference between prenatal and pediatric settings. There were no differences in sociodemographics between families that accepted versus declined secondary findings. CONCLUSION: The majority of families undergoing exome sequencing accepted secondary findings; this did not differ in prenatal versus pediatric settings. This highlights the need for guidance surrounding the offer of secondary findings in the prenatal setting.

Patient satisfaction and quality of care: a prospective study at outpatient dermatology clinics.

Patient satisfaction often is used as a proxy for quality of care, with physicians evaluated and reimbursed based on patient satisfaction scores. As a specialty, dermatology is lagging in quality improvement studies. To fill this gap, we conducted a prospective study of targeted interventions administered at outpatient dermatology clinics to determine if they resulted in statistically significant increases in patient satisfaction measures, particularly among Spanish-speaking patients. This study, along with the existing body of research, suggests the need for continued work to maximize patient satisfaction in dermatology.

OCHROCONIS GALLOPAVA ENDOPHTHALMITIS SUCCESSFULLY TREATED WITH INTRAVITREAL VORICONAZOLE AND AMPHOTERICIN B.

PURPOSE: Ochroconis gallopava is a darkly pigmented septated fungus that rarely infects humans, almost universally immunocompromised individuals. Only one previous case has been reported of O. gallopava endophthalmitis, in which the patient progressed to a visual acuity of no light perception. The authors currently describe the first successfully treated case of O. gallopava endophthalmitis. METHODS: A 65-year-old Hispanic woman on chronic immunosuppression after a right lung transplant was admitted to the hospital for O. gallopava respiratory tract infection and was found to have bilateral endogenous endophthalmitis. Examination revealed multiple, cream-colored, chorioretinal lesions in the fundus, including one near the temporal macula in the left eye. There was no diffuse vitritis. Visual acuity was 20/30 in both eyes at presentation but dropped to 20/400 in the right eye and counting fingers at 3 feet in the left eye over the hospital course despite receiving an intravitreal injection of voriconazole in the left eye and concurrent IV amphotericin B, posaconazole, and micafungin. The patient was then treated with multiple simultaneous intravitreal amphotericin B and voriconazole injections bilaterally, as well as IV posaconazole, which was switched to IV voriconazole for improved intraocular penetration. RESULTS: The chorioretinal lesions were noted to regress with treatment. Concomitantly, the patient's respiratory status improved, and she was discharged with a visual acuity of 20/40 in the right eye and 20/60 in the left eye. The patient completed a 1-year course of oral voriconazole as an outpatient without signs of recurrent activity. Seventeen months after the initial presentation, the patient had 20/40 vision bilaterally with a residual, white, fibrotic scar at the temporal macula in the left eye. CONCLUSION: This report describes the first successful treatment regimen against O. gallopava endophthalmitis using a combination of intravitreal amphotericin B and voriconazole injections, as well as IV posaconazole and voriconazole, which resulted in an excellent visual outcome.

Is it melanoma-associated retinopathy or drug toxicity? Bilateral cystoid macular edema posing a diagnostic and therapeutic dilemma.

PURPOSE: To report the clinical presentation, multimodal imaging, and management of a patient with metastatic melanoma who presented with cystoid macular edema (CME). OBSERVATIONS: We report a case of a 71-year-old Caucasian male with metastatic melanoma who presented with bilateral cystoid macular edema after being on treatment with a programmed T cell death ligand 1 inhibitor, MPDL3280, for 1 year. Multimodal imaging techniques, including color fundus photographs, autofluorescence, spectral domain optical coherence tomography (OCT), fluorescein angiography (Spectralis, Heidelberg, Germany), and spectral-domain OCT angiography (Zeiss; California, USA) were performed to evaluate the etiology of his CME and to monitor his response to treatment. Clinical examination and multimodal imaging revealed 1 + chronic vitreous cells, an epiretinal membrane, and mild macular edema in both eyes. Fundus autofluorescence showed paravenous hypoautofluorescence in the right eye and scattered hypoautofluorescent spots in the left eye. Optical coherence tomography angiography (OCTA) revealed mild drop out of superficial vessels in the peri-foveal region bilaterally. These findings were concerning for melanoma-associated retinopathy, drug-related uveitis, or activation of a previous chronic autoimmune process. The patient was started on prednisone 30 mg oral daily and ketorolac tromethamine 0.5% 1 drop four times daily. He was then treated with bilateral sustained-release dexamethasone intravitreal implants (Ozurdex). He had complete resolution of CME, and was tapered off of oral steroids within 6 weeks. CONCLUSIONS AND IMPORTANCE: Melanoma-associated retinopathy can be accompanied by CME, which presents a diagnostic and therapeutic dilemma in cases where a new drug has been recently initiated. By treating the condition locally, the ophthalmologist may be able to taper systemic immunosuppression more quickly.

Restricted Range of Motion and a Cold Upper Extremity in a Two-Year-Old Boy: Kaposiform Hemangioendothelioma of the Bone and the Brachial Plexus: A Case Report.

CASE: We report a case of kaposiform hemangioendothelioma (KHE) of the scapula in a 2-year-old boy with motor and sensory abnormalities of the left upper extremity, suggesting brachial plexus involvement. The locally invasive nature prevented resection; sirolimus therapy resulted in improvement of the motor and sensory impairment, as well as decreased tumor size on imaging. CONCLUSION: Osseous infiltration of KHE is known to occur, but its primary presentation in bone without skin involvement is rare and diagnostically challenging. Awareness of rare presentations of KHE, along with accurate histopathologic interpretation, is important to achieve a diagnosis and to differentiate KHE from more common vascular lesions (e.g., infantile hemangioma). Sirolimus therapy is emerging as a promising treatment for unresectable KHE.

Improving patient satisfaction in dermatology: a prospective study of an urban dermatology clinic.

Patient satisfaction has become an important measure of quality under the Patient Protection and Affordable Care Act. In this study, we assessed and analyzed patient satisfaction, nonattendance rates, and cycle times in an outpatient dermatology clinic. This study provides a snapshot of patient satisfaction in an urban dermatology clinic. Under the Patient Protection and Affordable Care Act, providers will be challenged to increase access to care and to validate quality of care through patient satisfaction.