Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Parliamentary Committees and Their Role in Modern Society

Samkvæmt umboðskenningum framselja umbjóðendur valdi sínu til fulltrúa sem eiga að vinna og taka ákvarðanir með hagsmuni umbjóðenda að leiðarljósi. Þetta samband milli umbjóðenda og fulltrúa býður upp á umboðsvanda þar sem fulltrúi gætir frekar eigin hagsmuna eða hagsmuna ákveðinna hópa frekar en umbjóðandans. Í þingnefndakerfinu er umboðsvandi alltaf til staðar þar sem vinnan sem fer fram í nefndum er á bak við luktar dyr, það er því hlutverk þingsins að hafa eftirlit með nefndum og takast á við umboðsvandann. Íslenska þingnefndakerfið er frábrugðið þeim kerfum sem tíðkast á hinum Norðurlöndunum og þegar valdheimildir íslenskra nefnda eru bornar saman við valdheimildir nefnda á hinum Norðurlöndunum kemur áhugaverður munur í ljós. Það er einnig áhugavert að skoða hvernig valdsvið nefnda hefur stækkað í kjölfar efnahagshrunsins árið 2008 og breytinguna á andrúmsloftinu á Alþingi. Á árunum fyrir hrunið var meðaltal nefndafrumvarpa 7,88 á ári en árið 2016 fór meðaltalið upp í 18 frumvörp á ári. Þegar íslenska nefndakerfið er skoðað og skipting nefnda á árum 1959-2015 kemur meðal annars í ljós að þingmenn frá landsbyggðar-kjördæmum hafa mun sterkari stöðu í þingnefndum. Þrjár mjög áhrifamiklar þingnefndir, fjárlaganefnd, landbúnaðar- og sjávarútvegsnefnd og samgöngunefnd, voru skoðaðar og skipting landsbyggðarþingmanna og þingmanna sem komu úr kjördæmunum á höfuðborgarsvæðinu. Í ljósi þessara upplýsinga er tekið dæmi um eitt af umdeildustu málefnunum í íslensku samfélagi, kvótakerfið, og hvernig vald þingnefnda getur tryggt að breytingar verða ekki gerðar á núverandi kerfi. Helsta niðurstaða þessarar ritgerðar er að núverandi kjördæmakerfi tryggir mun sterkari stöðu landsbyggðarinnar á Alþingi og í þingnefndum. Kerfið tryggir þannig að ákveðinn hópur í samfélaginu hefur aukin völd til að viðhalda þeim valdastrúktúr sem ríkir á milli landsbyggðarkjördæma og kjördæma á höfuðborgarsvæðinu. Önnur niðurstaða var sú að völd þingnefnda hafa aukist í kjölfar hrunsins en eftirlit með þeim hefur ekki aukist samhliða því. Því hefur þingið fært enn meiri völd í hendur þingnefnda, sem eins og niðurstöður þessarar ritgerðar benda til hallar að ákveðnum hópum samfélagsins og ýtir því enn meira undir umboðsvanda þingsins

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review

Five major psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, autistic spectrum disorder, and attention-deficit/hyperactivity disorder, show a shared genetic background and probably share common pathobiological mechanisms. S100B is a calcium-binding protein widely studied in psychiatric disorders as a potential biomarker. Our systematic review aimed to compare studies on peripheral S100B levels in five major psychiatric disorders with shared genetic backgrounds to reveal whether S100B alterations are disease-specific. EMBASE, Web of Science, and PubMed databases were searched for relevant studies published until the end of July 2023. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA) guidelines. Overall, 1215 publications were identified, of which 111 full-text articles were included in the systematic review. Study designs are very heterogeneous, performed mostly on small groups of participants at different stages of the disease (first-episode or chronic, drug-free or medicated, in the exacerbation of symptoms or in remission), and various clinical variables are analyzed. Published results are inconsistent; most reported elevated S100B levels across disorders included in the review. Alterations in S100B peripheral levels do not seem to be disease-specific

Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

Abstract Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate