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OBJECTIVE: To characterize the current distribution, composition, and practice patterns of multidisciplinary vascular anomalies (VAs) teams in the US. STUDY DESIGN: This is a cross-sectional survey of children's hospitals in the US offering VAs care. We approached 142 children's hospitals that provided care for VAs via email. The survey evaluated VA clinic location, medical staffing, research participation, and treatments offered. The survey was administered between October 2021 and July 2022. RESULTS: Participants from 95 eligible hospitals responded to the survey (response rate = 67%). Large areas of the Midwest and Northwest US had no available multidisciplinary VA teams or clinics. Most respondents worked at academic centers (89%), with 66% at a freestanding children's hospital, and 56% reported having a multidisciplinary clinic. Most common physician participants in clinic included hematology-oncology (91%), interventional radiology (87%), dermatology (85%), plastic surgery (81%), and otolaryngology (74%). Only 38% of programs included medical geneticists. Smaller hospitals had fewer medical and ancillary staff and offered fewer therapeutic options. Research was available at most larger institutions (69%) but less commonly at smaller hospitals (34%). CONCLUSIONS: Major portions of the US lack multidisciplinary VA care. Furthermore, VA programs vary in composition and geneticists are absent from the majority of programs. These findings should inform efforts to address disparate access and develop standards of care for multidisciplinary VA care in the US.

Assuntos

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Resumen Presentamos el caso de una paciente de 27 años con diagnóstico reciente de síndrome de CLOVES (Congenital, Lipomatous, Overgrowth, Vascular malformations, Epidermalnevi and Spinal/Skeletalanomalies and/orScoliosisSyndrome), quien fue diagnosticada previamente con los síndromes Klippel-Trenaunay-Weber y de Proteus. El síndrome de CLOVES es una patología poco frecuente y muchas veces el diagnóstico basado en la clínica suele complicarse por la superposición de signos y síntomas con otras patologías que también cursan con sobrecrecimiento.

Abstract We present the case of a 27-years-old patient with a newly diagnosis of CLOVES syndrome (Congenital, Lipomatous, Overgrowth, Vascular malformations, Epidermal nevi and Spinal/Skeletal anomalies and/or Scoliosis Syndrome). She has previously been diagnosed of Klippel-Trenaunay-Weber (at birth) and Proteus Syndrome (at 7 years). She presents dermatological alterations, syndactyly and overgrowth. CLOVES syndrome is a rare disease and often the clinic-based diagnostic is difficult due to overlapping signs and symptoms with other illnesses that also involve overgrowth.

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BACKGROUND: Small intestinal bacterial overgrowth (SIBO) affects up to 60% of patients with systemic sclerosis (SSc), and it improves with antibiotics. The addition of probiotics could lead to better results. AIMS: To evaluate the efficacy and safety of Saccharomyces boulardii (SB) versus metronidazole (M) versus M + SB for 2 months, to reduce gastrointestinal symptoms and SIBO assessed with hydrogen breath test in SSc. METHODS: An open pilot clinical trial performed in forty patients with SIBO and SSc (ACR-EULAR 2013) who signed informed consent. Three groups were assigned: M, SB, and M + SB, for 2 months. Hydrogen was measured in parts per million with a hydrogen breath test to evaluate SIBO. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) questionnaire was applied to quantify gastrointestinal symptoms with a raw score of eight symptoms. This study is registered in ClinicalTrials.gov with the following ID: NCT03692299. RESULTS: Baseline characteristics were similar between groups. The average age was 53.2 ± 9.3 years, and the evolution of SSc was 13.5 (1-34) years. After 2 months of treatment, SIBO was eradicated in 55% of the M + SB group: 33% of SB, and 25% of M. The SB and M + SB groups had decreased diarrhea, abdominal pain, and gas/bloating/flatulence, but M remained unchanged. Reductions in expired hydrogen at 45 to 60 min were as follows: M + SB 48% and 44%, M 18% and 20%, and SB 53% and 60% at the first and second months, respectively (p < 0.01). Adverse effects were epigastric burning and constipation in M (53%) and M + SB (36%), and flatulence/diarrhea in SB (22%). CONCLUSIONS: Metronidazole treatment is partially effective in SIBO, but S. boulardii in monotherapy or in combination improves the gastrointestinal outcomes in SSc.

Assuntos

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Truncular venous malformations and acquired functional or anatomical venous occlusions (or sub-occlusions) can be the cause of secondary lymphedema and even the cause of primary lymphedema when they are associated with lymphatic malformations (lymphangiodysplasia - LAD I, lymphadenodysplasia - LAD II, or a combination of both) in pediatric patients. This understanding recognizes the shared and successive embryogenesis of both systems. These conditions can exhibit hypertension in the venous pedicles intended for lymph-venous anastomosis, and this finding would be a formal contraindication to the procedure. However, this hypertension is a rarely considered condition and is not commonly identified. As a technique to solve this problem, we have combined Nielubowicz, Olszewski, Campisi, and Palma's proposals and created a lymph-venous anastomosis from the side with lymphedema and venous hypertension (lymphatic donor and venous recipient) with an internal suprapubic saphenous venous bridge (from the normal side to the lymphedematous side with venous hypertension) to enable a crossed inguinal lymphatic/venous rescue. We believe this newly synthesized approach will allow better clinical care of pediatric patients with complex and combined lymphatic-venous malformations and is worthy of further investigation.

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El síndrome de Sotos (SS) es una enfermedad genética con un patrón de herencia autosómico dominante, causado por haploinsuficiencia del gen NSD1 secundaria a mutaciones puntuales o microdeleciones del locus 5q35 en el que está ubicado el gen. Es un síndrome poco frecuente, presentándose en 7 de cada 100.000 nacimientos. El objetivo de este reporte es presentar el caso de una paciente de 4 años con retardo global del desarrollo, y hallazgos físicos especiales que sugerían un sindrome genético. Caso clínico: Paciente de 4 años, género femenino, cabello ralo, fascie triangular, fisura palpebral alargada, papadar ojival, mandíbula prominente, escápula alada y clinodactilia del quinto dedo de ambas manos. La prueba molecular de hibridación genómica comparativa por microarreglos, mostró microdeleción de la región 5q35.2 q35.3 de 2.082 MB, que incluye el gen NSD1. Conclusión: Proponemos realizar la prueba de hibridación genómica comparativa en pacientes con retraso global del desarrollo y hallazgos fenotípicos menores.

Sotos Syndrome (SS) is a genetic disease with an autosomal dominant pattern caused by haplo-insufficiency of NSD1 gene secondary to point mutations or microdeletion of the 5q35 locus where the gene is located. It is a rare syndrome, occurring in 7 out of every 100,000 births. The objective of this report is to present the case of a 4 year-old patient with a global developmental delay, as well as specific physical findings suggesting a syndrome of genetic origin. Clinical case: Female patient, 4 years of age, thinning hair, triangular facie, long palpebral fissure, arched palate, prominent jaw, winged scapula and clinodactilia of the fifth finger both hands. The molecular test comparative genomic hybridisation test by microarray was subsequently performed, with the result showing 5q35.2 q35.3 region microdeletion of 2,082 MB, including the NSD1 gene. Conclusion: Finally, this article also proposes the performing of comparative genomic hybridisation as the first diagnostic option in cases where clinical findings are suggestive of SS.

Assuntos

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UNLABELLED: Sotos Syndrome (SS) is a genetic disease with an autosomal dominant pattern caused by haplo-insufficiency of NSD1 gene secondary to point mutations or microdeletion of the 5q35 locus where the gene is located. It is a rare syndrome, occurring in 7 out of every 100,000 births. The objective of this report is to present the case of a 4 year-old patient with a global developmental delay, as well as specific physical findings suggesting a syndrome of genetic origin. CLINICAL CASE: Female patient, 4 years of age, thinning hair, triangular facie, long palpebral fissure, arched palate, prominent jaw, winged scapula and clinodactilia of the fifth finger both hands. The molecular test comparative genomic hybridisation test by microarray was subsequently performed, with the result showing 5q35.2 q35.3 region microdeletion of 2,082 MB, including the NSD1 gene. CONCLUSION: Finally, this article also proposes the performing of comparative genomic hybridisation as the first diagnostic option in cases where clinical findings are suggestive of SS.

Assuntos

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Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of NSD1 defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies PTEN in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in NSD1 molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%).

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Congenital unilateral overgrowth of the upper extremity affecting only the muscle tissue is rare. We describe on the clinical, histopathological, and neuroimaging findings in a 6-year-old girl with a congenital, non-progressive muscle enlargement of the entire left upper limb with an ipsilateral hand deformity. No cutaneous stigmata or additional features were detected. Sanger sequencing for the AKT1, PIK3CA, and PTEN genes identified an activating c.3140A>G, p.H1047R mutation in the PIK3CA gene from the affected muscle DNA. We demonstrate that isolated congenital muscular upper limb overgrowth with aberrant hand muscles is another condition related genetically to the PIK3CA-related overgrowth spectrum.

Assuntos