Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion

A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms.To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype.     

Signals of cell death and tissue turnover during physiological pregnancy,pre-eclampsia,and autoimmunity

Apoptosis normally occurs in the human placenta. As a consequence, cell blebs, post-apoptotic debris (also referred to as syncytial knots) and membrane microparticles are released into the blood of pregnant women. These events become prominent during the best-characterized pregnancy complication, pre-eclampsia. An excessive or deregulated cell death, which results in the generation of an overwhelming burden of apoptotic material, alarms the immune system. This plays a role in the pathogenesis of systemic connective tissue diseases and possibly of small vessels vasculitis. Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of normal pregnancy, indicating that physiologic pregnancy is a condition characterized by an activation of the innate immune system. Conversely, a failure in the physiologic termination of inflammatory events is probably a requirement for pre-eclampsia to develop. Here, we discuss recent findings suggesting a link between deregulated disposal of placental debris, the generation of endogenous pro-inflammatory signals (alarmins) and the widespread vascular inflammation that characterizes on one hand pre-eclampsia and on the other systemic autoimmune diseases.     

A case of acute esophageal necrosis (black esophagus) in a young man with Down syndrome

Acute esophageal necrosis, commonly referred to as ‘black esophagus?, is a rare clinical entity arising from a combination of ischemic insult, corrosive injury and decreased function of mucosal barrier systems and reparative mechanisms present in debilitating diseases. We describe the case of an 18-year-old man affected by Down syndrome, presenting with a streptococcus β-hemolytic group A infection of the upper airways. Although the patient was intensively treated with antibiotics, he developed a streptococcal toxic shock-like syndrome and died 5 days after admission. At autopsy, circumferential black discoloration of the esophageal mucosa that extended along the entire esophagus and ended abruptly at the esophageal-gastric junction was found. Neither ulceration nor esophageal perforation were present. Black esophagus is well known to the gastroenterology community, whereas it has been described only twice in the pathology literature. To the best of our knowledge, this is the first case ever reported complicating a streptococcal infection.     

Acute Reduction of Anandamide‐Hydrolase (FAAH) Activity is Coupled With a Reduction of Nociceptive Pathways Facilitation in Medication‐Overuse Headache Subjects After Withdrawal Treatment

Objectives.— We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication‐overuse headache, and (2) the effect of withdrawal treatment on both. Background.— The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication‐overuse headache. Methods.— We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication‐overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. Results.— A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication‐overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication‐overuse headache subjects before withdrawal treatment. Conclusions.— We demonstrated a marked facilitation in spinal cord pain processing in medication‐overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect.     

Erythrocytapheresis is a valid and safe therapeutic option in dysmetabolic iron overload syndrome

Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long‐term side effects. Here, we describe a case of metabolic syndrome‐related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443–447, 2016. © 2015 Wiley Periodicals, Inc.