OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Barthov syndróm je zriedkavé mitochondriové ochorenie viazané na chromozóm X. Je charakterizované širokým spektrom klinických príznakov a laboratórnych nálezov, z ktorých najtypickejšie je postihnutie srdca, myopatia, neutropénia, rastová retardácia, 3-metylglutakónová acidúria. Považuje sa za poddiagnostikovanú klinickú jednotku s rizikom náhleho úmrtia v detskom veku. V kazuistike prezentujeme prvého pacienta s dokázaným Barthovým syndrómom na Slovensku, u ktorého sa ochorenie manifestovalo v 3. týždni života kardiálnou dekompenzáciou s nálezom ľavokomorovej nonkompaktnej kardiomyopatie a hepatálnou dysfunkciou so závažnou koagulopatiou. Na základe metabolického vyšetrenia, klinických príznakov a pozitívnej rodinnej anamnézy – úmrtie dvoch chlapcov v dojčenskom období na ochorenie srdca, bola diagnóza Barthovho syndrómu potvrdená molekulovo-genetickým vyšetrením v 7. týždni života.
Barth syndrome is a rare mitochondrial disorder linked to chromosome X. It is characterized by a wide range of clinical signs and laboratory findings, most typically heart disease, myopathy, neutropenia, growth failure and 3-methylglutaconic aciduria. It is considered to be a underdiagnosed disease with the risk of sudden death in childhood. We report the first patient in Slovakia with proven Barth syndrome manifested by cardiac decompensation with the finding of left ventricular noncompaction cardiomyopathy and hepatic dysfunction with severe coagulopathy in the 3rd week of life. Based on the metabolic examination, clinical signs and a positive family history of two boys who died in infancy due to cardiac disorder, the diagnosis of Barth syndrome was genetically confirmed in the 7th week of life.
- MeSH
- Barth Syndrome * diagnosis genetics complications therapy MeSH
- Molecular Diagnostic Techniques methods MeSH
- Diagnosis, Differential MeSH
- Echocardiography methods MeSH
- Genetic Testing methods MeSH
- Cardiomyopathies diagnosis MeSH
- Clinical Laboratory Techniques methods MeSH
- Humans MeSH
- Mitochondrial Diseases diagnosis MeSH
- Neutropenia diagnosis MeSH
- Infant, Newborn MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Publication type
- Case Reports MeSH
Cieľ: V retrospektívnej štúdii analyzujeme súbor piatich pacientov s diagnózou entrapment syndrómu popliteálnej artérie, Uečených na našej klinike v rokoch 1999 a 2000. Výsledky a metódy: U piatich pacientov sme v rokoch 1999 a 2000 diagnostikovali na našom pracovisku vaskulámy entrapment syndróm. Z týchto 5 pacientov sme operovali 3 (spolu 5 operačných výkonov). Jeden pacient chirurgickú liečbu odnúetol, u jedného bola arteriálna lézia morfologicky nevhodná na revaskularizáeiu. Dvaja pacienti zo súboru mali bilaterálne postihnutie. Tri prípady sme riešili interpozíciou a. poplitea venóznym štepom Z dorzálneho prístupu. Dvakrát bola postačujúcim výkonom resekcia mediálnej hlavy m. gastrocnemius. Pacienti sú sledovaní v našej ambulancii (trvanie sledovania bolo v rozpätí 3 až 24 mesiacov, priemerná dĺžka sledovania 12,8 mesiaca), primárna hospitaUzačná priechodnosť rekonštrukcií je 100%; v sledovanom období nedošlo u žiadneho z pacientov k uzáveru rekonštrukcie. Záver: Podľa našich skúseností a v súlade s údajmi v literatúre, je pri chirurgickej liečbe entrapment syndrómu popliteálnej artérie najvhodnejšia úplná náhrada postihnutého úseku artérie autológnym venóznym graftom. Optimálnym sa javí dorzálny pristúp (Hammingov rez) s interpozíciou arteria popUtea autológnou vénou, pričom obe anastomózy sú typu end-to-end. V prípade, že arteriálna stena ešte nie je poškodená, postačujúcim výkonom je chirurgická dekompresia (myotómia), rovnako z dorzálneho prístupu.
Objective: In a retrospective study we analyze 5 patients with popliteal artery entrapment syndrome who were treated since 1999 to 2000 in our department. Methods and results: 5 patients were found to have popliteal vascular entrapment during a two-year period. From the total number of 5 patients, we performed surgery in 3 patients (5 operations). One patient rejected proposed surgical therapy, in another case the morphological lesion of the popliteal artery was not suitable for revascularisation. 3 patients underwent interposition of the diseased popliteal artery using a venous graft from í was sufficient. The study group is included in our follow up programme (median follow up 12.8 months, range from 3 to 24 months), primary and long term patency has been 100 %. Results: On the basis of our experience, we advice total replacement of the diseased popliteal artery. A dorsal approach (Hamming's „S" shaped incision) with interposition of the popliteal artery with autogenous venous graft, end to end anastomosis on both sides, seems to be the optimal solution. In case, the arterial wall is not irreversibly changed, surgical decompression (myotomy) is sufficient to prevent the development of symptomatic disease, also using the dorsal approach.
- MeSH
- Popliteal Artery surgery pathology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Syndrome MeSH
- Vascular Surgical Procedures methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
Úvod: Syndrom Freyové (aurikulotemporální syndrom) je častá komplikace chirurgie příušní žlázy, který je způsoben aberantním prorůstáním parasympatických vláken nervus auriculotemporalis do kožních potních žlázek. Typicky je syndrom charakterizován pocením, zarudnutím a pálením kůže parotické oblasti, zejména v návaznosti na chuťové podněty. Vytvoření interpoziční bariéry mezi kůži a lůžko po parotidektomii může vést ke snížení rizika této komplikace. Cíl: Cílem studie bylo stanovení četnosti výskytu syndromu Freyové u operovaných pacientů a zhodnocení účinnosti použití svalového laloku z musculus sternocleidomastoideus (m. SCM) v jeho prevenci. Soubor a metodika: Jde o retrospektivní studii. Soubor 167 pacientů, u kterých byla provedena parciální či totální parotidektomie v letech 2007–2011, byl rozdělen do dvou skupin. U první skupiny pacientů byla provedena rekonstrukce svalovým lalokem z m. SCM (n = 42), u druhé skupiny rekonstrukce provedena nebyla (n = 125). Diagnostika syndromu Freyové v pooperačním období byla stanovena na základě subjektivního hodnocení symptomů, údajů z dotazníku a objektivním průkazem Minorovým testem. Výsledky: Celkový výskyt syndromu Freyové činil 15 % (25/167 pacientů), ve skupině bez rekonstrukce 16 % (22/125), ve skupině s rekonstrukcí 7 % (3/42). Rozdíl mezi skupinami ve výskytu aurikulotemporálního syndromu byl dle Fisherova exaktního testu statisticky významný (p < 0,05). Závěr: Svalový lalok z m. SCM použitý k vytvoření interpoziční bariéry mezi kožní lalok a resekční lůžko po parotidektomii představuje jednoduchou, rychlou a efektivní metodu v prevenci syndromu Freyové po parotidektomii.
Background: Frey´s syndrome (auricotemporal syndrome) is frequent sequelae of parotid gland surgery caused by inappropriate regrowth of parasympathetic fibres of the auriculotemporal nerve into sweat glands of the skin. Typically, the syndrome is characterized by sweating, erythema and flushing of the skin overlying the parotid region, especially in response to taste stimuli. Placement of an interpositional barrier between the skin and the parotid gland can prevent these complications. Aim: The purpose of this study was to evaluate the incidence of Frey´s syndrome and the impact of using sternocleidomastoid muscle (SCM) flap on this syndrome. Material and methods: In a retrospective study, a series of 167 patients who underwent partial or total parotidectomy between January 2007 and December 2011 were divided into two groups. One group had an SCM flap reconstruction (n = 42), and the other group did not (n = 125). A subjective clinical evaluation, a questionnaire and the objective Minor´s test were used to diagnose the syndrome post-surgery. Results: The overall incidence of Frey´s syndrome was 15% (25/167 patients), 16% (22/125) in the non-SCM flap group and 7% (3/42) in the SCM flap group, respectively. There was a statistically significant difference between the two groups according to the Fisher´s frequency exact test (p < 0.05). Conclusion: The SCM flap, used as an interposing barrier between the overlying skin and the parotid bed following parotidectomy, is a simple, fast and efficient method for preventing Frey´s syndrome following parotidectomy. Key words: Frey´s syndrome – auriculotemporal syndrome – sternocleidomastoid muscle flap – parotidectomy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
- Keywords
- svalový lalok z musculus sternocleidomastoideus, parotidektomie,
- MeSH
- Surgical Flaps * MeSH
- Adult MeSH
- Sweating, Gustatory * epidemiology etiology prevention & control MeSH
- Neck Muscles * surgery transplantation MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Parotid Neoplasms surgery MeSH
- Parotid Gland surgery MeSH
- Postoperative Complications etiology prevention & control MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Plastic Surgery Procedures MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
Pathogenic gain-of-function variants in the genes encoding phosphoinositide 3-kinase δ (PI3Kδ) lead to accumulation of transitional B cells and senescent T cells, lymphadenopathy, and immune deficiency (activated PI3Kδ syndrome [APDS]). Knowing the genetic etiology of APDS afforded us the opportunity to explore PI3Kδ inhibition as a precision-medicine therapy. Here, we report in vitro and in vivo effects of inhibiting PI3Kδ in APDS. Treatment with leniolisib (CDZ173), a selective PI3Kδ inhibitor, caused dose-dependent suppression of PI3Kδ pathway hyperactivation (measured as phosphorylation of AKT/S6) in cell lines ectopically expressing APDS-causative p110δ variants and in T-cell blasts derived from patients. A clinical trial with 6 APDS patients was conducted as a 12-week, open-label, multisite, within-subject, dose-escalation study of oral leniolisib to assess safety, pharmacokinetics, and effects on lymphoproliferation and immune dysregulation. Oral leniolisib led to a dose-dependent reduction in PI3K/AKT pathway activity assessed ex vivo and improved immune dysregulation. We observed normalization of circulating transitional and naive B cells, reduction in PD-1+CD4+ and senescent CD57+CD4- T cells, and decreases in elevated serum immunoglobulin M and inflammatory markers including interferon γ, tumor necrosis factor, CXCL13, and CXCL10 with leniolisib therapy. After 12 weeks of treatment, all patients showed amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean; range, 26%-57%) and 40% (mean; range, 13%-65%), respectively. Thus, leniolisib was well tolerated and improved laboratory and clinical parameters in APDS, supporting the specific inhibition of PI3Kδ as a promising new targeted therapy in APDS and other diseases characterized by overactivation of the PI3Kδ pathway. This trial was registered at www.clinicaltrials.gov as #NCT02435173.
- MeSH
- Lymphocyte Activation drug effects MeSH
- Chemokines blood MeSH
- Molecular Targeted Therapy * MeSH
- Demography MeSH
- Child MeSH
- Phenotype MeSH
- Class I Phosphatidylinositol 3-Kinases antagonists & inhibitors immunology metabolism MeSH
- Immunoglobulin M blood MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Infant MeSH
- Rats MeSH
- Humans MeSH
- Lymph Nodes drug effects pathology MeSH
- Mutation genetics MeSH
- Child, Preschool MeSH
- Pyridines pharmacokinetics pharmacology MeSH
- Pyrimidines pharmacokinetics pharmacology MeSH
- Spleen drug effects pathology MeSH
- Immunologic Deficiency Syndromes drug therapy enzymology immunology pathology MeSH
- T-Lymphocytes drug effects immunology MeSH
- TOR Serine-Threonine Kinases antagonists & inhibitors metabolism MeSH
- Transfection MeSH
- Organ Size MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Rats MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, N.I.H., Intramural MeSH
