Sisekõrva implantatsioon. Sisekõrvaimplantaadiga patsiendid Eestis

Kuulmisnõrkus on kõige enam levinud sensoorne haigus kogu maailmas. Erinevate kuulmisnõrkuse vormide puhul on varajane rehabilitatsioon äärmiselt oluline, et vältida patsiendi sotsiaalse isolatsiooni kujunemist ning säilitada tema elukvaliteet ja karjääriväljavaated. Sensorineuraalse kuulmisnõrkuse puhul on esmaseks rehabilitatsioonivahendiks kuuldeaparaat, mille võimaluste ammendumisel rakendatakse sisekõrva implantatsiooni (SI). Esimene sisekõrva implantaat paigaldati 1978. a. Tänapäeval on SI laialdaselt aktsepteeritud kompleksne kirurgiline ning kuulmis- ja kõnestamisalane ravimeetod mõlemapoolse sügava sensorineuraalse kuulmisnõrkusega patsientidele. SI peamisteks kandidaatideks on kaasasündinud sügava kuulmisnõrkusega lapsed. Käesolev artikkel annab ülevaate kuulmisnõrkuse klassifikatsioonist ja diagnostikast, vastsündinute audioloogilisest sõeluuringust, samuti SI hetkeseisust Eestis. Eesti Arst 2009; 88(3):182−18

Pärilik ehk geneetiline kuulmislangus

Kuulmislangus on kõige enam levinud sensoorne haigus kogu maailmas. Varajase ehk kõne-eelse kuulmislanguse esinemissagedus arvatakse olevat 1–2 juhtu 1000 lapse kohta ning pooltel juhtudest on see pärilik. Geneetiline kuulmislangus jagatakse sündroomseks vormiks, mille korral kuulmislangus on seotud teiste elundite anomaaliatega, ja mittesündroomseks ehk isoleeritud vormiks. Eesti Arst 2007; 86 (4): 254–26

Kuulmislanguse geneetilised põhjused Eesti lastel ning leitud genotüübi ja fenotüübi omavaheline võrdlus

Eesmärk. Selgitada välja kuulmislanguse (KL) geneetilised põhjused Eesti lastel ja kirjeldada nende fenotüüpi. Metoodika. Uuringus osales 233 KLiga last, kellele tehti APEX-geenikiibi analüüs 201 erineva mutatsiooni suhtes 8 pärilikku KLi põhjustavas geenis (GJB2, GJB3, GJB6, GJA1, SLC26A4, SLC26A5, 12S-rRNA ja tRNA (Ser) geenid). Tulemused. Leidsime 115 patsiendil (49%) GJB2 mutatsiooni vähemalt ühes alleelis, neist 100 lapsel esines vähemalt ühes alleelis mutatsioon c.35delG. 5 patsiendi (2%) KL oli tingitud kaasasündinud tsütomegalovi irusinfektsioonist. Sündroomne KL kinnitati 7 uuritaval. Kogu genoomi genotüpiseerimisplatformi analüüs tehti 28 patsiendile, selle tulemusel leidsime 4 erinevat potentsiaalselt patogeenset deleteerunud kromosoomipiirkonda. Järeldused. Kõige sagedasem lapseea KLi põhjustav mutatsioon on c.35delG, mille osakaal KLiga laste hulgas on 75% GJB2 geeni mutatsioonidest. Uuringu tulemusena selgus või täpsustus KLi etioloogias geneetiline faktor 140 patsiendil (60%). Eesti Arst 2010; 89(12):781−78

Natural history of KBG syndrome in a large European cohort

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.</p

Varajase algusega kuulmislanguse geneetilised põhjused Eesti lastel

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Varajase ehk kõne-eelse KL esinemissagedus arvatakse olevat ligikaudu 1–2 juhtu 1000 lapse kohta. Kuni 60%-l juhtudest on tegemist päriliku ehk geneetilise KL-ga, ülejäänud juhtudel aga omandatud ehk kahjulikest väliskeskkonna faktoritest põhjustatud KL-ga. Hetkel on teada mitusada KL-st põhjustavat geeni, kuid see on siiski vaid umbes 1/3 kõikidest KL-ga seotud geenidest. Geneetiline KL jagatakse omakorda sündroomseks ja mittesündroomseks vormiks. Kõige sagedamini on tegemist autosoom-retsessiivse pärilikkusega mittesündroomse KL-ga. Euroopa erinevates populatsioonides kõige sagedamini esinev pärilikku kuulmislangust põhjustav mutatsioon on GJB2 geenis asuv mutatsioon c.35delG, mida leitakse umbes 30%-l KL-ga patsientidel. Meie töö eesmärkideks oli määrata GJB2 geeni mutatsioonide c.35delG ja p.M34T esinemissagedus Eesti vastsündinute populatsioonis; välja selgitada KL geneetilised põhjused Eesti lastel ja kirjeldada nende fenotüüpi; kirjeldada väikeseid submikroskoopilisi kromosomaalseid ümberkorraldusi ja määrata molekulaarse analüüsiga kaasasündinud tsütomegaloviirusinfektsiooni esinemine KL-ga lastel. Mutatsioonide c.35delG ja p.M34T esinemissageduse skriininggrupis oli 998 anonüümset vastsündinut, kes olid järjestikku sündinud Eesti erinevates piirkondades ühe kuu jooksul. KL-ga laste uuringugruppi kuulus 233 patsienti, kellel oli diagnoositud lapseea algusega KL. Uurisime KL-ga lapsi kuulmislanguse DNA analüüsiga 8 geenis (GJB2, GJB3, GJB6, GJA1, SLC26A4, SLC26A5, 12S-rRNA and tRNA (Ser)) 201 mutatsiooni suhtes APEX meetodil. Töö tulemusena leidsime Eesti vastsündinute anonüümsel skriiningul mutatsiooni c.35delG kandluseks Eestis 1:22 ja mutatsiooni p.M34T kandluseks 1:17. KL-ga laste grupi uuringul leidsime, et GJB2 geeni mutatsioon c.35delG on ka Eestis kõige sagedasem KL-e põhustaja ja teisel kohal on mutatsioon p.M34T. Mutatsioonide c.35delG ja p.M34T esinemissagedus nii KL-ga laste kui ka skriinitud anonüümsete vastsündinute hulgas on Eestis kõrgem kui enamikes Euroopa riikides. Ülegenoomsel genotüpiseerimisel Illumina geenikiipidega leidsime kolmel patsiendil kolm erinevat deleteerunud kromosoomipiirkonda ja kaasasündinud tsütomegaloviirusinfektsioon oli KL-e põhjuseks viiel lapsel. Uuringu tulemusena selgus või täpsustus KL etioloogiline geneetiline faktor 140 patsiendil (60%).Hearing loss (HL) is the most common sensory disorder wordwide, one to two children in 1000 are born with HL. In 50-60% of the cases with HL are hereditary (genetic) and in 40-50% of the cases of hearing loss acquired due to environmental factors. Genetic HL is divided into syndromic and non-syndromic forms. The non-syndromic autosomal-recessive forms of HL are more common. Mutation c.35delG accounts for the vast majority of the GJB2 mutations detected in Caucasian populations. The aim of our study was to establish the prevalence of c.35delG and p.M34T mutations in GJB2 gene among Estonian general population; to investigate genetic background in Estonian children with HL and to describe their phenotype; to evaluate the occurrence of small submicroscopic chromosomal rearrangements and the incidence of cytomegalovirus (CMV) infection in children with HL. The general Estonian population study group consisted of 998 anonymous newborn samples whose were partially dissociated. The study group of children with HL consisted of 233 children. We investigated them by APEX gene array analysis, which covers 201 mutations in eight different genes (GJB2, GJB3, GJB6, GJA1, SLC26A4, SLC26A5, 12S-rRNA and tRNA (Ser)). The results of our study we found carrier frequency for c.35delG mutation 1 in 22 and for p.M34T mutation 1 in 17. The prevalence of the carrier frequencies of the mutations c.35delG and p.M34T in the GJB2 gene in Estonia is the highest of results found in European populations. The mutations found most frequently among Estonian children with early onset HL were c.35delG and p.M34T. Whole genome array analysis was indentified in three patients three potentially pathogenic chromosomal deletions. In five patients the congenital CMV infection was found by DNA analysis. In conclusion the etiology of HL was established or specified in 140 investigated children (60%)

Sport professionnel : Conventions collectives, toute une coordination !

Le sport professionnel fait l'objet de différentes conventions collectives avec en particulier la CCNS et des accords sectoriels conclus dans différentes disciplines sportives. La superposition de leurs champs d'application pose la question de la coordination de leurs clauses

Natural history of KBG syndrome in a large European cohort

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: −0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11

Natural history of KBG syndrome in a large European cohort

KBG syndrome is characterised by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterise natural history of KBG syndrome. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array-CGH and NGS approach investigated both genomic CNVs/SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while OFC (median value: -0.88 SD at birth) normalised over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia, and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ENT evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11

Natural history of KBG syndrome in a large European cohort

Abstract KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: −0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11