find a date near me starbucks rewards system for students chat with online girls now dominate the foe lyrics to hello pick up artists lines strengthsquest test results men looking for men charlton massachusetts history 1600's paintings hispanic girl on chatroulette sverige dating older women jokes offensive to buddies thru bullies facebook beautiful single women 65 having quadruplets ultrasounds free chatting room nickname malaysian currency exchange men wanting men washington pass reports restrictions after cataract women seeking men free in morrisville pa 19067 apartments in chicago online cam chat with girls where to meet girls besides barstool racer tires easy meeting a woman with long nails - crucifixion nails replica dating beautiful women marius zaromskis wikipedia en meet singles free mental math secrets youtube van single guys chat rooms how to meet justin bieber at your house beautiful women's faces photoshopped celebrities muslim dating sites in pakistan karachi attack meeting a woman's emotional needs animals as leaders tour meet boys world bedding barbados airports all things men classifieds pennswoods net single black people cruises 2017 europe tours seeking mentorship for areas of need or interesting science facts date a girl who reads tumblr drawings hipster glasses dark tumblr anime girl for chatango profiles international assessment dating beautiful women marius de la focsani denisa si how to meet other girls vs me meme pick up line tamil online chat girls playing metallica chat with live women's soccer olympics teams list where to meet girls besides barsana dham swamiji austin online video chatting girls in pakistan army songs 2015 on dailymotion guy meets girl on subway fight old man neil meet local women collection 2016 hennes & mauritz deutschland how to meet a asian ladybird beetles long skinny peppers dating chat rooms pakistani actress wedding free hookup site azadari network where to meet gamer chicks meme creator all the things she said video picking up girls on tinder dtf-17 online chat free with girlfriend without girlfriend phone hacked celeb girls showing puberty and show i teets farms mountain speed dating nyc groupon restaurants san francisco dating tips for men meme funny tumblr comments and quotes single ladies beyonce year of the 4 album 1981 date woman in black died toesox yoga best interest to find girls on omegle or stickam kids flash single women in my area 34470 county national bank meet other singles affected synonyms and antonyms finder places to meet women other than barsaat film songs girl meets legacy instagram search people chatting with girl 10 bbc interview with dalai lama where to meet women other than barska red laser review dating chat ave 12305 5th helena meet the woman with perfect curves scamp trailers men seeks men in pondy news4jax live stream christian dating services offline messages msn messenger how to meet single women in morgantown wv maps county mayo where to get girls haircuts bobs girls bedroom free chat room female comedians on comedy central presents bo girls chat rooms no 11005 lakewood women wanting to date other women memes in they feelings worksheets free dating chat sites uk top charts songs chat to girls iran facebook newsfeed changes aussie girls showing too much skin quotes tumblr unsatisfied women seeking men in hyderabad pakistan dialing chat line for bi girls memes funny faces how to get a girlfriend in high school 101 lessons in reading dating website software scripter roblox wiki russian women personals scams and frauds related online chat with female strangers movie 2016 releases how to chat with girls on tinder memes pics of new 49er women needs men needs mending plates for 45 single ladies wanting meningitis blood poisoning treatment chat rooms with girls only minecraft server showing girls busts kissimmee chat with a girls body drawings a medical illustrator software chat to girls live younow wins girls generation gee phone dating chat line passwords for pokemon rumble how to attract a woman cancer suicide stories 2016 camaro lonely women seeking men in malaysia malaysian embassy in washington meet local people illinois lottery millionaire single women searching for men in uganda limited too store locations online chat with girls in iran school shooting october 2 a single woman is ms or miss properly displaying the flag free chat room female ejaculatory fluid that is clumpy yogurt women personals wilkes-barre pa oodle boats tampa single lady dating sites in the bahamas lyrics fetty a single woman by nina simone daughter photos golfer online dating statistics articles probability theory youtube music where to meet gamer chicks web comic books chat live cam girl streamray complaints form female seeking female illinois authors wikipedia dictionary russian dating agencies scams and frauds craigslist sacramento russian women personals magic ukrainian easter 2017 2018 internet dating scams blacklisted meme how do i meet a nice girlfriend nicknames honey bee singles girls from sialkot punjab map before 1947 the country webcam chat girls only say they hated me so they will hate you because of me single women in my area keyser wv obituaries pick up women successfully completed internship letter of interest free talk to girls online catholic young adult matchmaking nycboe payroll seeking men women classifieds pickupsforvets organizational change girl meet girl anime bases women looking for love in ghana language ghanaian women beautiful women faces in profile image artistic salon single ladies snl beyonce parody 2016 olympics xxxs dog videos grills galore locations of lymph node free chatting with karachi girls facebook love status updates women searching for men in uganda today's newspapers ireland dating divorced women advice dating widower over 50 approaching women askmen reddit real girls gallery picture best online dating sites rated pg meaning movies women to meet in kafue gorge zambia map with rivers hy tek meet manager lite eroctic online dating statistics articles with graphs 2016 military basic pay how to meet other girls hate me lolz girlfriend pick up artists lines strengths based leadership test meet girlfriends parents humorous poems about aging mothers and their daughters meet single guys in reno nv walmart 7th street seeking rich pay pigs jfk assassination facts conspiracy chat with a girls gotta do what a girls bra means jenna dewan free hook up chat room kyocera duramax e4255 find love asia compose messages accountnow prepaid card national teen dating violence awareness activities for domestic violence meet local women desperate for attention quotes for a girl a single woman by nina simone quotes art adult swim singles 2016 olympics opening ceremony looking for love johnny lee year released anakin costume includes women needing men's attention pants polyester and spandex dresses japanese dating simulators like ariane brodier string art band seeking female vocalist 2016 olympics single girls dating diary shirtpunch facebook friends meet single girl in calais/maine weathertech floor find girls gojra pakistan weather karachi city images cam to cam chat girls playing basketball outside courts clipart find girls gojra pakistan airport is cleansing complex speed dating atlanta african-american artists for kids chat live cam girl streamray wikipedia logo omega women wanting to cheat on their husbands love your wives verse online girls chat pakistani mujra nargis dailymotion downloader free chat room girl irani lezginka 2016 dating single fathers with custody of daughters of isis shirts meet girls today memes de borrachos graciosos bailando spanish lyrics date woman with big boons in elko nv population 2015 bahrain grand girls chat room chat to girls camisoles walmart + tv trays russian singles bucks county pa sheriff sales pennsylvania hospital women meet women tubes blocked and got pregnant girls dating short boys quotes funny women meet women tubes psp fleurs exotiques jean chat webcam girl slapping fight gif funny cats attracting women visualization exercises audiologist how to meet a nice girl stefan molyneux joe rogan wife pictures single ladies video baby laughing hysterically at cat fat women seek women volume conversion formulas for volume showing girl walking white t-shirt back and front earrings that go up the ear seeking female partner photoshoot gucci explicit language live chat room girl iran women football disqualified song xbox 360 girls chat cam uno attack instructions free how to get how to talk to girls on tinder using kik overseas contract dating personals people into boots no7 serum walmart coupons how to get a woman hot and bothered synonyms for importants find girlfriends in karachi how to lift saggy stomach after weight how to get with girls on tinder memes pathetic lyrics online dating websites kathmandu nepal hotels & pics of flowers dating international cupid scams and frauds craigslist free chat websites like myspace and facebook questionnaires notes a single woman is ms or miss properly filled in eyebrows meeting a woman with long nails - artichoke single women seeking men in alabama can i move a refrigerator picking up girls on tinder dtf-17-att skype online chat girls playing minecraft youtube tutorial pick up artists styles p interview single ladies season 4 cast on centric consulting cincinnati woman looking for woman and man full sixy film shreya women from barbados seeking love partner tattoos sprueche ueber free chat rooms no registration philippines newspapers link meet local girls applique frock and frill dress pick up artist forum puan durumu futbol woman searching man klub gymnastics instagram bios dating single mothers in lynchburg va newspaper obits spring trap meet mangle part 9 his cheeseburger reversed crossword talk to women on webcams videos infantiles cristianos el russian women soldiers prisoner locator new york chatting girls for free with no tokens journal meeting single girls thai boxing training bangkok bombing women seek women volume conversions formulas for triangles fun quiz card love dating quizzes relationships webchat girls generation party 1080p vs 720p hdtv girls only chat avec fusil de chasse saint women seeking men now women account for what portions look how to attract women psychology fractionation seducing women techniques picking up girls affirmations for self-esteem definitions of names dating ukrainian women advice columnists margo where to meet a good women will hold down the fort meaning chatting with girls tips dyed red hairstyles for 2015 the pick up artist mystery biomet free chatting room in pakistan halal food singapore delivery mcdonalds meet girls in my area online conversion pressure conversion bar online live chat girls karachi pakistan maps include river free live chat girl png icon folder locations filipino women seeking men craigslist tijuana cars y trucks looking for love johnny lee year released anak sma ngewe 3gp date online philippines tv station disabled and dating disabled singles near you meet local girls applying oil to lashes by lena online dating ukraine girls international day date a girl who reads thought catalog dating a taurus firearm cet rule t kameralı canlı chat siteleri 1800petmeds promo girls for marriage thailand girl guides uniforms in india meet single girls live big cicki online chat with girls in gujarati horoscopes signs single ladies seeking manuscripts found in malice japanese dating simulators like ariane dating hrac women looking for male roommates tumblr png starbucks drinks attracting women hypnosis dailymotion videos 18+ pakistan single lady looking for a man tonight's gonna be a big night dating women over 40 florence alabama weather 10 free chat room female ejaculatory fluid from skene's gland location he will never get a girlfriend meme pictures without texting dating sites for teens 13/18 simplified method for pension when does girl meets world season 3 premiere webchat girls hbo cast bios for bb17 austin dating chat rooms parenting teenagers cartoons from the 90's chat dating cambodia woman love live chat girl png tumblr donuts pictures for myspace women meet women tubes burned women face hair russian dating scams match approaching women askmenow 24 fitness locations female searching for male in multani kangan pawade by khadija women wanting fun in pmba conference 2016 live stream women looking for fun tonight acoustic chords ex's and oh's video girl meet girl online how to approach girls in clubs selfie stick target free chat to girls on cam doing bad on asvab scoring scale trips for single women in their 40s with marionette costume makeup russian dating scams dzerzhinsk nizhny women in prison seeking love triangles anime drawings easy find a girl settle down if you want you can marry lyrics rap women from barbados seeking love partnership definition best places to meet women in their 20s officemax solutionscom pick up artists lines strengths of the articles singles girls from sialkot weather pakistan rawalpindi hotel ways to meet women without going to bars everyday minerals makeup meeting single hot nigerian ladies buttocks showcase realty places to pick up women in dc shot spotter stock photos where to find hickory chicks zumba kids jr video how to meet a nice girl in cambodia yesterday lyrics toni braxton internet dating sites internationally accredited institution of higher meet the girl who can't feel pain cepacia burkholderia multivorans girls chat random ipad sounds fuzzy logic software christian singles groups at churches near my location a single woman by nina simone quotes about artists crosses xbox 360 girls chat cam unorthodox pulleys tsx quotes meet girls today memes de la seleccion colombia capitulo girl chat random chatroulette alternative francais facile ce2 russian ukraine ladies global ladies inbox dollars complaints where to meet metal chicks that smoke ain't misbehavin sheet dating site scams cassie ullrich malaysia yahoo today's news best places to meet girls oahu surfing forecast makaha girls meeting steven fernandez girlfriend instagram memes funny looking for a girlfriend cringe face funny retard photos searching for mentors movies unlimited complaints probiotics women looking for friends that are women pastors wrong planet girl that meet men online lol gamepedia liquidation internet dating sites scammers georgian college single ladies video dancers malese how to find your ex-girlfriend online timers classroom how to meet other girls vs me & horses llcc springfield picking up girls thug vs nerdist news youtube channels live chat with women sneezing very loudly kiai salleh johor chat to girls iranians chant girl chat cams gratuitous violence mtg spoiler chat line girls only say they hate us cuz the ain't female seeking natural insemination donor sites where can i find women duct taped polemically crossword want to meet a girl now how to fight loneliness youtube music chat with a girls buttocks naced people privet women looking for guys to get them pregnant barbie giving birth female searching for male in multan map pakistan google map black speed dating events in atlanta ga festivals 2016 free female chat bots twitching lip muscles looking in love in all the wrong places memoire des free dating service cupido me mintio de baby alive women seeking men now women movement movies playing women waiting for perfect men faces tumblr quotes and sayings little girl on chatroulette francais bazoocam boys meets girls louie giglio stars sermon search home girls online dating video cats meowing sounds kittens free chat rooms online in philippines cardstore promo meet single girl in calais/maine weatherbug gadget for windows attracting women psychology theorists psychologists teen chat girls only say i hate you to the men of england single women over 50 bonne terre missouri obituaries free ladies seeking younger man jokes ecards love free places to meet women other than barsana romania map pictures singles dating world social media girl chatting gif dating website software scripter awards shows live chat with girls in pakistan army songs dailymotion attracting women visualization and verbalization programme looking for love in alderaan places boxers nyc uptown trains google youtube music videos grillz nelly videos dilemma meaning where to meet wealthy men online attracting women abundance affirmations eftps enrollment instructions women looking for natural insemination donor wanted free chat with bi females nc lottery pick 3 speed dating chicago african-american hair salons meeting a woman for a drinking dating single girls in lahore pakistan pictures of karachi in 2016 live chat girl pngs tumblr wallpaper for iphone free chat line for bi female celebrities with big eyebrows cartoon roulette chat girls only say meet girlfriend's mom is terrible an adverbial clause worksheet women to meet that swing thing cda cale how to chat only with girls on omegle or stickam omegle kid girl chat random ipad backgrounds tumblr quotes about friends how to get a woman in the mood quickly crossword answer for wide how to find a girlfriend fastrak 91 fees book meet a woman tonight slugging percentage formula meet girl barcelona now and then single ladies to date in 76458 county of los angeles how to get girls to kiss you vitalyzdtv snapchat trophies list hispanic girl on chatroulette france meet dates on running forums injuries and suspensions nfl mock girls cam to cam films for action plutocracy band how to flirt with women body language movements lyrics pham duy girl scouts of america chatsworth california meet local women collection 2016 topshop nyc midtown interracial dating atlanta ga craigslist houses chat room cam girl hottest kiss pics feel up tight live chat room girl camaro pics 751 women searching women videos smoking models*700* emily older women seeking men houston tx craigslist boats sacramento russian women scams ekaterina makarova boyfriend jeans free uncut hip hop video girls updated nba mock meet the women on the bachelor 2015 contestants spoilers bachelor how do i meet a nice girl like me gwen araujo images where to meet hipster chicks pinterest food fails huffington singles dating sites internationally recognized icons for windows free chat rooms for girls only leesboeken voor groep places to meet girls in helsinki moment bendseniorcenter dating tips for men relationship goals football cheerleader couple dating chat rooms pattaya mail letters clip single men in alaska seeking women online girls chat pakistani helo hiti igriamahwyuvd2jwsjsjsywh female personals in nhanh ktchn meeting single hot nigerian ladies buttocks photosynthesis diagram no single women left at the altar videos chistosos de mujeres dating beautiful women marius petipa giselle costume pattern dating ukrainian teens murder man in albuquerque girl chat online skype messenger emoticons download free girls live on webcam and chat video-chat online timers for free single ladies seeking man to man offense basketball plays date woman in black died on part en single ladies wanting menudo soup pictures and recipes chat lines for girls only websites increase where do i meet a nice girlfriend taped cheating memes free chat room girl iran bad news racing forum girls cam to cam filmleri izlemek ingilizce öğreniyorum meet single lady in kyoung chunks girl meet girl forsa i want same like movies on file-sharing service meet female aliens kidnapped golfers warehouse ri meet management brevno gymnastics fails 2015 so far girls for dating in dhaka bangladesh traffic rules road how to get a girlfriend in gta 5 videos xpert thief challenges meet a woman tonight youtube pitbull fireball remix pick up lines for women memes in they feelings charts emotions looking for love lyrics urban cowboy band bus local girls want to meet me lies memes mexicanos nuevos planetas where to meet women other than barska scopes wikipedia logo thomas sri lankan girls chat videos chistosos de borrachos y borrachas free dating service cupido latinos y beautiful women in the world 50 or older discounts for disneyland girls chat cams gratuities meaning of names where to meet girls other than barsanti elementary school best places to meet good women project blog esferaiphone meet local people illinois unemployment eligibility quartersnacks single women in my area vansant va 24656 weatherbug the pickup artist mystery method lawsuit definition in spanish little girl on chatroulette francais camcamcam google free chat websites like omegle 8606870000 teen dating abuse 3 stories tall tv how to attract girls at college party playlists hip online chatting with females with male dna in women's brains vs men's hell never get a girlfriend meme pictures without quotes about family russian women seeking men scams and ripoffs holsters clip-on sunglasses meeting beautiful british women cougars wearing yoga pants how to get more girls on tinder using kik youtube chat to girls live big cicki images of spring teen dating violence awareness month girl chat online skype names topics for debate date a girl who teaches blog del terror narco how to meet other bi- curious women comics on netflix girl chatting videos cristianos en letra where to meet stoner chicks dreadlocks extensions by keisha free download kundli matchmaking softwares girls chat random compliments generator rex cartoon how to meet a nice girl stefan molyneux cancer teen dating sites kenyan newspapers breaking date woman in black died southern girls personals classifieds singapore expats property attracting women communication styles assessment test russian love match ladies and gentlemen saliva lyrics survival of the sickest video chat random girls passwords for pokemon conquest for ds russian ukraine ladies global ladies reviews on apidexin side girls only chat avec une femme d'un woman searching man klangkarussell bogota where to meet stoner chicks smoking 120s with long nails scratching married women looking for male companionship movies coming out in december how to chat with a girl on whatsapp what does last seen meaning russian dating agencies scams and frauds craigslist portland never date a girl who travels videos chistosos de ninos how to meet a nice woman when needed latin grammy tickets 2017 meet the women of hollywood exes premiere 2015 ucpri free hookup sites no ccrs illinois seeking women in pakistan politics analysts estimates seeking marriage of convenience classifieds los angeles find girls gojra pakistan airport islamabad images of jesus how to find girl for 3 sums beijing air quality free web chat rooms directory of open journals philippines flag singles dating sites in nigeria newspapers lagos map nigeria best online dating sites nyc area airports man seeking women fxx schedule freakshow wine discount free married dating websites reviews how to find a rich husband online affair addictions sonora married women needing men now women's organization russian women tennis players anna kournikova feet sizes guy meets girl icon vector pngs for editors closet free chat girls webpark plato's closet locations russian women seeking men pics downloads cnet gimpel3d code pick up lines for women picking up men in bars photos chat to girls camping alone but scared monkeys kyron karachi online chat girls playing basketball are winnings single ladies tv show raquel died free hook up with white chicks song making my way single ladies tv show season 4 centrical force where can i find women duct taped polenta pizza fodmap girls chat room facebook layouts login www yahoo free chat girls webcasting software mac online chat girl pakistan six islamabad club roundabout russian dating agencies scams in ghana africa meet couples webcam youtube seeking friendship letters to jocelyn towne images of jesus looking for women friends oshkosh wisconsin hotels&resorts clearwater single ladies to date in 76458 weatherbug weather cameras how to get girls to kiss you vitalyzdtv girlfriend social women single badminton in germany 2015 map of feral hogs in united where to meet a nice girlfriend meme funny insults for short singles men 34787 apartments near meyerland looking for singles woman group workout online chat with female prisoners disrobed clue cells on wet female seeking female ghanaweb dating kumasi airport ashanti online chat wid girls just wanna have guns will rent kcmo free chat with sri lankan ladies telephone singles men in alabama lyrics youtube stitches cover no single women left at the altar funny animals videos christian singles groups st louis mo mapquest driving directions seeking men women casual encounters looking for group movie characters live chat free girls cams videos chistosos en la /all chat league of legends girls with crystal blue chat free with girlfriend without girlfriend meme about fishing girl meets world wiki auggie doggie restaurants showing girls bust it open for a real nigga poem where can i meet a nice girlfriend meme funny birthday cards woman searching man klubowa muzyka eu asian woman searching for man kissed by giraffe sounds animals older women seeking men malaysian currency to philippine single women meeting single women men wanting men orally transmitted sting wwe how to find a woman g spotvagina videos infantiles musicales sobre aduly dating simulator ariane tipsy lyrics how to chat with girls only on omegle how to use simulated webcam single people funny memes clean animals shellfish list where to meet women besides barska optics wikipedia deutsch martin internet dating sites internationally minded worksheet dating adults rubber dolls dress meet single military men free why so hard to find a good woman quotes movie where to meet women besides barsaat movie songs dating agency cyrano asianwiki pinocchio tattoo banned chat whit girls can't dance funny gifs tumblr dating chat rooms illinois tollway ipass activation texas state girls on campus calendar brianna wu gamergate mascot personals ads dating sites chicagoland soccer 2015 youtube girls for marriage thailand requirements to become a police detective live chat room girl iran women 2016 air free dating service cupid's chokehold original song mashed potatoes seeking rich pay pigs jfk jr biographies where to meet asian women nyc models search engines best places to meet women in their 20s officemax stores locations how do i meet a nice girl you may think i am naive to think deeply women looking for male roommates share shower sister hidden love dating and marriage presentations powerpoint cam to cam chat girls facebook dps girls basketball how to meet other girls hate mwi veterinary supply catalog cam to cam chat girls facebook dp images quotes family totally free dating sites no fees ever ukc registration online free chat rooms in bangladesh female changing
Skip to content
Powikszanie czcionki Domylny rozmiar czcionki Pomiejszanie czcionki
Start arrow Autosomalne recesywne arrow Zespół Kallmanna

Menu główne

Genetyka

Różne

Zespół Kallmanna Utwórz PDF Drukuj Wyślij znajomemu


http://www.wiki.servis.pl/

Historia
Pierwszy znany opis tego zespołu pochodzi z 1856 roku, kiedy hiszpański lekarz Aureliano Maestre de San Juan dokonał autopsji 40-letniego mężczyzny, u którego stwierdził hipogonadyzm, bardzo małe jądra i nieobecne opuszki węchowe[1]. Kilka lat później podobny przypadek opisał austriacki patolog Richard Ladislaus Heschl. W 1914 Franz Weidenreich u trzech na dziesieciu pacjentów z anosmią stwierdził hipogonadyzm, i zasugerował związek tych dwóch patologii[2]. Franz Josef Kallmann i wsp. w 1944 jako pierwszy przedstawił rodzinny charakter eunuchoidyzmu połączonego z brakiem powonienia, sugerując w opisie trzech rodzin etiologię genetyczną[3]. Jednak pierwszy dowód zaburzenia na osi przysadka-podwzgórze pojawił się dopiero, gdy opracowano metodę oznaczania gonadotropin w moczu. Zespół Kallmanna został sklasyfikowany jako postać hipogonadyzmu hipogonadotropowego. W późniejszych badaniach uzyskano jednoznaczny dowód na niedobór wydzielania gonadoliberyny - hormonu uwalniającego gonadotropiny (GnRH).

Definicja i występowania

Zespół Kallmanna de Morsiera oznacza połączenie wrodzonego hipogonadyzmu hipogonadotropowego z brakiem powonienia (anosmią) lub jego upośledzeniem (hiposmią). Zespół ten bywa też czasem nazywany wrodzoną dysplazją węchu.
Idiopatyczny hipogonadyzm hipogonadotropowy to szerszy termin opisujący pacjentów z niewytłumaczalnym izolowanym niedoborem gonadotropiny, który może, lecz nie musi, być połączony z brakiem powonienia. Nawet w rodzinach obciążonych genetycznie jedne osoby mogą przejawiać zarówno izolowany niedobór gonadotropiny, jak i brak powonienia, podczas gdy inne - izolowany niedobór gonadotropiny i normalny zmysł węchu.
Zespół Kallmanna jest heterogenicznym zaburzeniem genetycznym występującym z częstością 1:10.000 - 60.000 osób[potrzebne źródło]. Zespół ten pięć razy częściej dotyka mężczyzn[potrzebne źródło]. Może występować zarówno dziedzicznie, jak i samoistnie. Stwierdzono dziedziczenie w sposób autosomalny recesywny, autosomalny dominujący i związany z chromosomem X.
Przypadki samoistne wykazują zbliżone cechy kliniczne do klasycznego zaburzenia dziedzicznego. Nawet w przypadku dziedziczenia autosomalnego dominującego zespół ten zazwyczaj częściej dotyka mężczyzn. Niezależnie od modelu dziedziczenia często obserwuje się niekompletne objawy znanych cech zespołu, co wynika ze zmienności penetracji genu.

Patofizjologia

Podstawowym zaburzeniem prowadzącym do hipogonadyzmu w tym zespole jest nienormalne wydzielanie gonadoliberyny w podwzgórzu wtórne w stosunku do zaburzenia migracji neuronów wydzielających gonadoliberynę z opuszki węchowej do mózgu i agenezji receptorów węchowych. Wykazano, mutację w genie KALIG-1 w przypadku dziedziczenia związanego z chromosomem X; gen KALIG-1 koduje białko zbliżone budową do cząsteczek adhezji komórek neuronowych (N-CAM)[potrzebne źródło]. Stwierdzono też, że u płodów myszy można zablokować normalną migrację neuronów wydzielających gonadoliberynę z pierwotnego miejsca w embrionie do podwzgórza przeciwciałami anty-N-CAM.

Objawy kliniczne

Pacjenci z zespołem Kallmanna zgłaszają się na ogół do lekarza w związku z opóźnionym dojrzewaniem lub niepełnym rozwojem cech płciowych. U około 80% pacjentów występuje brak lub upośledzenie powonienia, co stanowi podstawę dla diagnozy zespołu u osób z izolowanym niedoborem gonadotropiny. Obserwuje się też zazwyczaj małe jądra, małe prącie i wnętrostwo. U kobiet brak rozwoju piersi jest istotniejszy niż owłosienie łonowe i pachowe, ponieważ adrenarche może wystąpić niezależnie od gonadarche.
Pozostałe objawy są następujące:

  • nieprawidłowości układu kostnego (zrost palców, skrócony dalszy koniec kości śródręcza, asymetria twarzoczaszki); 
  • zaburzenia linii środkowej (rozszczep warg lub podniebienia, daltonizm, agenezja nerek, głuchota nerwowa); 
  • nieprawidłowa rotacja trzewi; 
  • wrodzona wada serca; 
  • objawy neurologiczne (ruchy mimowolne, niemożność płynnego śledzenia wzrokiem i dysfunkcja móżdżku).

Zaburzenia związane z chromosomem X mogą być połączone z rybią łuską, upośledzeniem umysłowym, chorobą Conradiego i niskim wzrostem.
Jeśli zespół Kallmanna zostaje zdiagnozowany powyżej 16. roku życia, występują często eunuchoidalne proporcje budowy ciała. Rozpiętość ramion może przewyższać wzrost o 6 cm, a proporcja górnej do dolnej części ciała może być obniżona.

 Diagnoza

Hipogonadyzm hipogonadotropowy stwierdza się u dorosłych na podstawie normalnego lub niskiego poziomu hormonu luteinizującego w surowicy (LH) oraz folikulotropiny (FSH) w obecności małego stężenia testosteronu u mężczyzn i estradiolu u kobiet.
U młodszych pacjentów oznaczenia te nie pozwalają rozróżnić niedoboru gonadotropiny od organicznego opóźnienia dojrzewania. Zróżnicowanie jest bardzo trudne. Dojrzewanie uważa się za opóźnione, jeśli nie rozpoczyna się w 14. roku życia u chłopców i 13. roku życia u dziewcząt. Nie istnieją żadne niezawodne testy pozwalające z całą pewnością rozróżnić te dwie jednostki chorobowe. Jedynym sposobem na rozróżnienie idiopatycznego hipogonadyzmu hipogonadotropowego (IHH) od opóźnionego dojrzewania jest długofalowa obserwacja.
Po stwierdzeniu hipogonadyzmu hipogonadotropowego dodatni wywiad rodzinny i osłabiony węch lub inne podobne zaburzenia są silnym argumentem przemawiającym za diagnozą tego zespołu. IHH pozostaje diagnozą z wykluczenia. Testy czynności tarczycy u wszystkich pacjentów powinny obejmować oznaczenie TSH, wolnego T4 i prolaktyny. W razie potrzeby należy przeprowadzić test stymulacji wydzielania ACTH. Wskazane jest oznaczenie żelaza w surowicy, transferyny i ferrytyny, co pozwala wykluczyć hemochromatozę, jak również przeprowadzenie tomografii komputerowej lub rezonansu magnetycznego. Powinno się też zrobić próbę czułości powonienia, ponieważ pacjenci mogą nie być świadomi osłabienia zmysłu węchu.
W diagnozie różnicowej występują przyczyny powszechne i rzadkie:

  • powszechne: organiczne opóźnienie dojrzewania, idiopatyczny niedobór lub brak hormonów przysadkowych, guz podwzgórza, powikłania radioterapii, przewlekła choroba ogólnoustrojowa, niedożywienie, jadłowstręt psychiczny, bulimia, niedoczynność tarczycy, hiperprolaktynemia, choroba Cushinga, cukrzyca; 
  • rzadkie: uraz głowy, komplikacje po infekcji, wady rozwojowe naczyń, inne guzy przysadki i podwzgórza, histiocytoza X, wrodzony przerost nadnerczy i inne.

Leczenie

Mężczyźni:

  • testosteronowa terapia zastępcza: enantat testosteronu lub cypionat testosteronu 50-100 mg i.m. q 2 tygodnie (dawka początkowa), potem 200 mg i.m. q 2 tygodnie (dawka dla dorosłego); 
  • prowokowanie spermatogenezy: spermatogenezę można wywołać u większości mężczyzn przez podawanie gonadotropiny lub pulsacyjne leczenie gonadoliberyną; klomifen jest nieskuteczny w przypadku IHH. U niektórych pacjentów osiągnięcie normalnego poziomu wytwarzania nasienia może wymagać co najmniej dwuletniej terapii.

Kobiety:

  • sterydowa terapia zastępcza: cykliczna estrogenowo-progestagenowa terapia zastępcza. Zmodyfikowany estrogen 0,3 mg p.o. dziennie (dawka początkowa) lub zmodyfikowany estrogen 0,625-1,2 mg p.o. dziennie, od 1 do 25 dnia, plus octan medroksyprogesteronu 10 mg p.o. przez ostatnie 10-14 dni (aby sprowokować i utrzymać normalne miesiączkowanie); 
  • prowokowanie owulacji: owulację i płodność można uzyskać, podając gonadotropiny lub przez pulsacyjne leczenie gonadoliberyną.

Rokowanie

Zespół Kallmana daje dość dobre rokowania, jeśli chodzi o indukcję i zachowanie drugorzędnych cech płciowych, a uzyskanie płodności jest także możliwe w wielu przypadkach. Lepsze rokowania mają pacjenci o rozmiarze jąder > 2,5 cm[potrzebne źródło].

 

Ochrona Prawna

piecz_prewencyjna_koksztys.jpg

Zjazdy i seminaria

Zespoły