LYMPHODYSPLASIA AND KRAS MUTATION: A CASE REPORT AND LITERATURE REVIEW.

Cardio-facio-cutaneous (CFC) syndrome is a very rare and sporadic disease whose characteristics include dysmorphic facial appearance, ectodermal abnormalities, cardiac abnormalities, growth retardation and neurodevelopmental delay. This syndrome is classified as one of the RAS syndromes which are caused by altered signal transduction of the RAS/MAPK (mitogen activated protein kinase) pathway due to the mutation of genes including BRAF, MEK1/2, HRAS and KRAS. Other RAS syndromes, such as Costello syndrome and Noonan syndrome, share clinical features with CFC.

Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment.

Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role of the lymphatic system.

Pleural fluid effusion particularly chylothorax is a relatively rare occurrence in the newborn, but when it occurs it is often life-threatening. In this article, we describe and illustrate the morphologic features of the visceral and parietal pleura including pleural lymphatics and the physiology and pathophysiology of pleural fluid balance. The role and function of the lymphatic system in controlling the volume and composition of pleural liquid are detailed and a conceptual scheme presented.

Evaluation of tibial osteopathy occurrence in neurofibromatosis type 1 Italian patients.

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype.

Congenital fetal and neonatal visceral chylous effusions: neonatal chylothorax and chylous ascites revisited. A multicenter retrospective study.

This retrospective study was carried out at eight Neonatal Intensive Care Units (NICU) Centers worldwide on 33 newborns presenting at birth with pleural, pericardial, or abdominal chylous effusions. Diagnosis of chylous effusion is based on findings of fluid with a milk-like appearance, a concentration of triglycerides in pleural effusion >1.1 mmol/l, and a total cell count >1,000 cells/ml with a predominance of >80% lymphocytes.

Are there lymphatic vessels in the placenta?

The role of lymphatics in placentation has been scantily studied and the true existence of placental lymphatics is under debate. Numerous blood and lymphatic-lineage molecule markers are now available and they are expressed in human placental tissue. D2-40 expression at the placental stromal level seems to indicate that network-forming, podoplanin-expressing cells may act as a reticular-lymphatic-like conductive network.

Perinatal deaths and lymphatic system involvement: a diagnostic flow-chart applying immunohistochemical methods.

A diagnostic flow chart is presented for use in case of perinatal death or still birth with non-immune hydrops fetalis, visceral effusions, or increased nuchal translucency. Immunohistochemical staining with CD-31, CD-34, D2-40, and smooth muscle actin is recommended.

Congenital lymphatic dysplasia in Kabuki syndrome: first report of an unusual association.

Kabuki syndrome was first described in Japan in 1981 as a rare disorder of unknown cause. Its main features include characteristic facies, postnatal growth retardation, and mental delay. To date, there is no molecular marker for Kabuki syndrome, which is considered genetically heterogeneous and still is a clinically-based diagnosis.

Immunohistochemistry in non-immune hydrops fetalis: a single center experience in 79 fetuses.

The objective of our study was to evaluate the usefulness of immunohistochemical (IHC) staining techniques in the etiological diagnosis of non-immune hydrops fetalis (NIHF). The records of all 1,098 autopsies performed between January 1987 and May 2008, by the Division of Fetal Pathology of the University of Genoa, were reviewed and all 79 fetuses diagnosed with NIHF were re-evaluated. Additional IHC staining using antibodies that specifically stain blood and lymph vessels (CD31, CD34, smooth muscle actin antibody, D2-40) were performed.

Microsurgery for lymphedema: clinical research and long-term results.

Objectives: To report the wide clinical experience and the research studies in the microsurgical treatment of peripheral lymphedema.

Methods: More than 1800 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic microvascular procedures recognize today its most exemplary application in multiple lymphatic-venous anastomoses (LVA).

The role of lymphoscintigraphy in the diagnosis of lymphedema in Turner syndrome.

Lymphedema can be present in patients affected by Turner syndrome (TS) with the dorsum of the hands and feet most commonly affected. This lymphedema results from underdevelopment of the lymphatic system before birth, and it usually decreases during childhood. The aim of our study was to evaluate the role of lymphoscintigraphy as a diagnostic tool in patients with TS to assess possible impairments in the lymphatic system.

Selective D2-40 lymphatic endothelium immunoreactivity in developing human fetal skin appendages.

D2-40 is a novel monoclonal antibody that recognizes a 40,000 Da O-linked sialoglycoprotein podoplanin. Although its use is becoming more common, little work has been done with human foetuses. We initiated an evaluation of D2-40 antibody immunoreactivity in developing cutaneous adnexa of human fetuses at various gestational ages.

Nuchal translucency and lymphatic system maldevelopment.

We describe the histological examination of 18 aborted fetuses that had increased nuchal translucency (NT) between 11(+0) and 13(+6) weeks' gestation. The aim of this study was to assess the corresponding NT anatomic features by immunohistochemical (IHC) investigation. A morphological study was performed using lymphatic and blood endothelial specific markers, as well as smooth muscle actin (SMA).

Congenital lymphatic dysplasias: genetics review and resources for the lymphologist.

Diagnosing congenital lymphatic dysplasia and counseling the parents of babies with possible genetic conditions represents a difficult task. This article attempts to provide a guide to establishing genetic tools and a reference library for use in the diagnostic work-up of congenital lymphatic diseases. The tools that are outlined herein are not meant to replace genetic counseling; their role is merely to facilitate the interaction between lymphologist and geneticist.

Etiology of nonimmune hydrops fetalis: a systematic review.

Hydrops fetalis (HF) indicates excessive fluid accumulation within the fetal extravascular compartments and body cavities. HF is not a diagnosis in itself but a symptom, and the end-stage of a wide variety of disorders. In the era before routine immunization of Rhesus (Rh) negative mothers, most cases of hydrops were due to erythroblastosis from Rh alloimmunization, but nowadays, nonimmune hydrops fetalis (NIHF) is more frequent, representing 76-87% of all described HF cases.

Peroxisomal acyl-CoA-oxidase deficiency: two new cases.

We report on two new patients with straight-chain acyl-coenzyme A oxidase deficiency. Early onset hypotonia, seizures and psychomotor delay were observed in both cases. Plasma very-long-chain fatty acids were abnormal in both patients, whereas the plasma levels of phytanic acid, pristanic acid, the bile acid intermediates DHCA and THCA, and erythrocyte plasmalogen levels were normal.

Lymphatic dysplasias in newborns and children: the role of lymphoscintigraphy.

We performed lymphoscintigraphy in 15 patients (newborns and children) affected by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is mandatory in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, to obtain very early diagnosis and begin treatment.

Pediatric lymphedema and correlated syndromes: role of microsurgery.

Authors report modern diagnostic and therapeutic procedures used in the correct assessment and treatment of congenital lymphatic and chylous disorders. Lymphatic dysplasias can be clinically represented only by peripheral lymphedema or be associated with more complex dysfunctions of chyliferous vessels and the thoracic duct (chylous ascitis, chylothorax, etc.) It is, therefore, useful to perform a complete diagnostic evaluation of each patient before carrying out any therapeutical approach.

Immunohistochemical studies in a hydroptic fetus with pulmonary lymphangiectasia and trisomy 21.

This case report presents a hydroptic trisomy 21 fetus affected by lymphatic dysplasia with no other malformations. Our studies using CD31, CD34, smooth muscle actin, desmin, and D2-40 antibodies immunohistochemistry confirm the diagnosis of severe pulmonary lymphangiectasia associated with lymphangiectasia ih the mediastinum and small bowel.

Reliability assessment of glucose measurement by HemoCue analyser in a neonatal intensive care unit.

Background: Rapid and reliable bed-side determination of blood glucose concentration is very important in the management of acutely ill infants and especially in premature newborns. HemoCue is an easy-to-use glucose analyser. The aim of the present study was to examine the usefulness of the HemoCue glucose analyser compared to a reference plasma glucose method (SYS, BM/Hitachi 747/737) in a neonatal intensive care unit (NICU).

The lymphatics in the pathophysiology of thoracic and abdominal surgical pathology: immunological consequences and the unexpected role of microsurgery.

The authors report their experience in the diagnosis and treatment of lymphatic and chylous disorders in the thoracic and abdominal areas. Sixteen patients (10 adults, 6 children) affected by primary chylous ascites with associated syndromes and consequent immunological incompetence were studied. Diagnostic investigations included abdominal sonography scans, lymphoscintigraphy, and lymphography combined with computed tomography and laparoscopy.

Microsurgery for treatment of peripheral lymphedema: long-term outcome and future perspectives.

Authors report over 30 years of their own clinical experience in the treatment of chronic peripheral lymphedemas by microsurgical techniques performed at the Center of Lymphatic Surgery of the University of Genoa, Italy. Over 1,500 lymphedema patients were treated with microsurgical techniques. Derivative lymphatic-venous techniques were most often used.

Congenital pulmonary lymphangiectasia.

Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth.