A Case Report of Pseudoxanthoma Elasticum with Rare Sequence Variants in Genes Related to Inherited Retinal Diseases.

A case of a patient with an early and severe visual impairment is described. Due to the occurrence of skin papules a suspect of pseudoxanthoma elasticum (PXE) was posed. PXE is a rare autosomal recessive disease clinically characterized by skin, cardiovascular and ocular manifestations, these last being those that most severely affect patients' quality of life. A whole exome sequencing approach focusing on 340 genes related to the calcification process and/or to inherited retinal diseases (IRDs) was performed. Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. The presence of calcified elastic fibers was assessed by ultrastructural analysis on a skin biopsy. Diagnosis of PXE was based on clinical, biomolecular and morphological results, although the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient also in prognostic and therapeutic perspectives. Data indicate that genetic screening using a wide-spectrum analysis approach is essential to assist ophthalmologists in improving patient counseling.

From Clinical Diagnosis to the Discovery of Multigene Rare Sequence Variants in Pseudoxanthoma elasticum: A Case Report.

Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disease clinically characterised by early cutaneous alterations, and by late clinically relevant ocular, and cardiovascular manifestations. ABCC6 genetic tests are used to confirm clinical PXE diagnosis, but this strategy may be rather challenging when only one ABCC6 pathogenic variant is found. A next-generation sequencing approach focusing on 362 genes related to the calcification process and/or to inherited retinal diseases was performed on a patient with clinical PXE diagnosis (skin papules and laxity, angioid streaks, and atrophy) who was carrier of only one ABCC6 rare sequence variant. Beside ABCC6, several rare sequence variants were detected which can contribute either to the occurrence of calcification (GGCX and SERPINF1 genes) and/or to ophthalmological manifestations (ABCA4, AGBL5, CLUAP1, and KCNV2 genes). This wide-spectrum analysis approach facilitates the identification of rare variants possibly involved in PXE, thus avoiding invasive skin biopsy as well as expensive and time-consuming diagnostic odyssey and allows to broaden and to deepen the knowledge on this complex rare disease and to improve patients' counselling, also with a future perspective of personalised medicine.

Phenotypic Features and Genetic Findings in a Cohort of Italian Pseudoxanthoma Elasticum Patients and Update of the Ophthalmologic Evaluation Score.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification genetic disease mainly caused by ABCC6 rare sequence variants. The clinical phenotype is characterized by typical dermatological, ophthalmological and cardiovascular manifestations, whose frequency and severity are differently reported in the literature. METHODS: A retrospective study was performed on 377 PXE patients of Italian origin, clinically evaluated according to the Phenodex Index, who underwent ABCC6 biomolecular analyses. Moreover, 53 PXE patients were further characterized by in-depth ophthalmological examinations. RESULTS: A total of 117 different ABCC6 rare sequence variants were detected as being spread through the whole gene. The severity of the clinical phenotype was dependent on age, but it was not influenced by gender or by the type of sequence variants. In-depth ophthalmological examinations focused on the incidences of coquille d'oeuf, comet lesions, pattern dystrophy-like lesions, optic disk drusen and posterior-pole atrophy. Conclusion: Given the large number of patients analyzed, we were able to better evaluate the occurrence of less frequent alterations (e.g., stroke, myocardial infarction, nephrolithiasis). A more detailed description of ophthalmological abnormalities allowed us to stratify patients and better evaluate disease progression, thus suggesting a further update of the PXE score system.

Adaptive Optics Imaging in Patients Affected by Pseudoxanthoma Elasticum.

PURPOSE: To describe the retinal findings of patients affected by pseudoxanthoma elasticum (PXE) using a multimodal imaging approach including flood-illumination adaptive optics ophthalmoscopy (AO). DESIGN: Retrospective case series. MATERIALS AND METHODS: Patients affected by PXE were retrospectively studied. Clinical data, color, infrared and autofluorescence fundus imaging, optical coherence tomographic scans, and AO examinations were collected. Furthermore, the photoreceptor count was assessed. PXE diagnosis was confirmed by a positive skin biopsy and/or genetic testing. RESULTS: Twenty-one eyes of 18 patients (11 females and 7 males) were included in the study. In 3 patients, both eyes were studied. The mean age at examination was 37.7 ± 16.4 years (range 14-66) and the mean best-corrected visual acuity (BCVA) was 0.1 ± 0.2 logMAR (range 0-1). We identified 3 types of angioid streaks (AS) using AO: "crack," "band," and "hypopigmented." The first 2 were very similar and they differed in size; the third type showed specific clinical features. Comet lesions appeared as hyper-reflective round lesions on AO imaging. In all eyes, the cone mosaic appeared reduced inside the streaks compared to the neighboring areas (13,532.8 ± 1,366.5 cones/mm2 vs 16,817.1 ± 1,263.0 cones/mm2 respectively). CONCLUSION: Using AO imaging in PXE-related retinopathy, we were able to observe the presence of the photoreceptors within the angioid streaks, differentiate 3 types of angioid streaks, based on size and reflective features, and identify the very small crystalline bodies not identifiable using other retinal imaging techniques.

[The treatment of female stress urinary incontinence (SUI) using fascia lata in a rural hospital]. / Tratamiento de la incontinencia de orina de esfuerzo (IUE) femenina mediante el empleo de fascia lata en un hospital rural.

OBJECTIVES: Pubovaginal sling has been the treatment of choice for female SUI over the last two years. Those made with autologous materials have demonstrated a lower rate of complications. We present our experience using autologous fascia lata. METHODS: Between May 2005 and July 2006 we performed 10 procedures through a suprapubic approach. In eight cases they were ascended to the retropubic space using needles, and in 2 cases we employed the vaginal tunneler (Tyco). In the 8 initial cases both sling branches were anchored to the Cooper's ligament. In the remainder two cases they were anchored to the fascia of the obliquus externus muscle. RESULTS: Mean age was 57.7 years; mean follow-up time was 14.8 months (6-20). In 6 cases cystocele was simultaneously corrected. Hospital stay was 72 hours. In two cases, section of the autologous sling was required due to excessive correction. Four patients keep using pads; nevertheless, all 10 patients refer no SUI. Post-operative urine culture was positive in four patients, with negative controls. One case presented vaginal candidiasis. CONCLUSIONS: Autologous fascia lata pubovaginal sling is an effective low cost treatment, with a low complication rate.

Tratamiento de la incontinencia de orina de esfuerzo (IUE) femenina mediante elempleo de la fascia lata en un hospital rural / The treatment of female stress urinary incontinence (SUI) using fascia lata in a rural hospital

Objetivo: El sling pubovaginal ha sido en los últimos años el tratamiento de elección para la IUE femenina. Los de material autólogo han demostrado el menor índice de complicaciones. Presentamos nuestra experiencia empleando fascia lata autóloga. Método: Entre mayo de 2005 y julio de 2006 realizamos 10 tratamientos por vía suprapúbica. En 8 casos se ascendieron al espacio retropubiano mediante agujas y en 2 casos se empleó un tunelizador vaginal (Tyco®). En los 8 iniciales se fijaron ambas ramas del sling al ligamento de Cooper. En los 2 restantes se fijaron a la fascia del oblicuo mayor. Resultados: El promedio de edad fue de 57,7 años; el tiempo de seguimiento promedio fue de 14,8 meses (6-20). En 6 casos se corrigió simultáneamente un cistocele. La internación fue de 72 hs. En 2 casos se requirió la sección del sling autólogo debido a hipercorrección. Cuatro pacientes continúan empleando toallas higiénicas, sin embargo las 10 pacientes no refieren IUE. En 4 pacientes el urocultivo posoperatorio fue positivo, con controles negativos. Un caso presentó una candidiasis vaginal. Conclusión: El sling pubovaginal con fascia lata autóloga es un tratamiento efectivo de bajo costo, con una baja tasa de complicaciones (AU)

Objectives: Pubovaginal sling has been the treatment of choice for female SUI over the last two years. Those made with autologous materials have demonstrated a lower rate of complications. We present our experience using autologous fascia lata. Methods: Between May 2005 and July 2006 we performed 10 procedures through a suprapubic approach. In eight cases they were ascended to the retropubic space using needles, and in 2 cases we employed the vaginal tunneler (Tyco®). In the 8 initial cases both sling branches were anchored to the Cooper's ligament. In the remainder two cases they were anchored to the fascia of the obliquus externus muscle. Results: Mean age was 57.7 years; mean follow-up time was 14.8 months (6-20). In 6 cases cystocele was simultaneously corrected. Hospital stay was 72 hours. In two cases, section of the autologous sling was required due to excessive correction. Four patients keep using pads; nevertheless, all 10 patients refer no SUI. Post-operative urine culture was positive in four patients, with negative controls. One case presented vaginal candidiasis. Conclusions: Autologous fascia lata pubovaginal sling is an effective low cost treatment, with a low complication rate (AU)