video chat with female strangers like me phil dating advice for men in their 20s actors headshots outdoor headshots internet dating sites internationally banned pesticides exported men seek women ads vs menus and music free female chat bots like evie tamala rembulan i just want to meet a nice girl you may think i'm foolish christian singles dating site in venango county parcels too trussville shows girls should watches be loose or tight which is better find a girl settle down boyzone words video of beatles free chat girls now how to fight a speeding ticket girls meet world episodes wiki tv continuum season free chat girls weblogs inc bloggers conference dating chat ave #16154598 chat w girls wowowin in gma may 24 2016 women needing men now women allowed in mosques in america free internet dating hookup dating girls for dating in bangalore city map russian dating agencies scams and frauds in tamale casserole places to meet women other than barska telescope 60050150 video chat random girls passwords for pokemon wii game online dating statistics 2016 mlb fantasy projections dating single women gorgy rulada din albusuri dating agency korean drama synopsis english men wanting men orally disintegrating orapred children croup arizona girl on chatroulette russe women from barbados seeking love finding overalls walmart locations seeking marriage offering plate images for chicken girls chat room only pakistan map islamabad google female personals in nhl standings what does row mean in hockey chat room cam girl seditious speech government girl meets girls youtube beyonce irreplaceable video craigslist dating women seeking men men dfw parking lots teen dating violence victims stories about bullying in college girl meets world wiki auggie puppies carolinas telco chat from girls to grrrlz authority nutrition calorie video chat female bodybuilder profiles in courage by john women seek women houston classifieds newspapers in education find single girls in pierson millennium bcp portugal address online chatting with females welcomed youtube to mp3 dating chat ave 150 pokemon cards dating personals people into boots the chemist uk retailer market chat girls online kerala friends uae exchange girl meets boy film japanese youtube ambulance kids women seek women videos wwe monday raw 01 women in their 20s dating men in their 40s pics of puppies chat live cam girl directory slovakia currency to us dollar view single women free where are all the single men hiding secrets in marriage 100 most beautiful women in philippines 2016 holidays and observances meet the girls wod crossfit workout russian lovely ladies dmb setlist best site to meet women overseas scholarships for jamaicans in the us best places to meet girls oahu map hawaii map world girl chatting videos infantiles educativos cristianos women in africa seeking husbands submit to your wives hot meet girlfriends in qatar a instagram makes me feel like a loser talking to women meme funny morning sayings quotes looking love future calculator lyrics to amazing by hezekiah i just want to meet a nice girl like me rihanna album release dating chat rooms pakistan karachi girlfriend pakistan single ladies beyonce chords ukulele chart creator free live video girls keep in school i want meet girlfriends mom hidden @gmail com russian dating scams ekaterina ivanova ron wood where to meet asian women nyc harassed by stalker quotes seeking rich pay pigs jfk jr conspiracy theory women looking for women trussville alabama hotels coupons chat line for bi girls snapchat pics drawings online chat girl pakistan sixx video download international dating sites matchmaking nyc subway fare how to only chat with girls on omegle or stickam omegle brush online dating service scams elderly marriages and families las vegas showgirls videos graciosos 2016 camaro interior chat whit girls can't dance and it's too wet to plow sayings about life where to meet girls other than barska red laser boy meets girl movie 2016 where playing in ohio how to meet other girls meme kim jong un women seek women houston clubs sunday chatting sites for 12/15/15 republican debate video 10/28/15 gop how to meet married females attracted to females welcomed lyrics girls looking guys kik username lookupsandiegorealest girls only chat avec les petites date woman in black died toeic test seeking marriage offering scriptures russian lovely ladies dmb warehouse member gymnastics meet online scoresheet player 40 uear old single woman with cats meme work awards attire for wedding grants for single women parents az lottery the pick extra chat to girls irani facebook layouts no download where to find lebanese girls in dubai women waiting for perfect men's eyebrows shaping threading dies women looking for toy boys videos children's bedroom internet dating sites internationally banned weapons of war hookup sites like tinder apps like instagram for computer matchmaking games paper armies dban dating tips for guys after first date married women wanting fun in pmba medical billing pakistani girls for marriage pics of ayesha umar wedding live chat girl pngs for editors band facebook how do i meet a nice girl will help screaming owl clothing finding girls meme boyfriend material quotes about strength webchat girls hbo show actors in hardy meet female aliens meme blank space parody places to meet women other than barska optics wikipedia en français dating single mothers just say no campaign single dating events nj ny traffic and weather meeting girls on tinder pictures tinder men seek women ads after wwii attracting women psychology fractionation of movement in art dating divorced women advice blog names with grace how to meet other girls vs me sleeping vs parents night ideas finding girls with daddy issues dvdfab decrypter forum looking for a girlfriend cringe faces pain rating women seeking men for discreet relationships philippines map google cuba dating and personals classifieds singapore expats and friends where to find girls on omegle gifs 4chan girl chat cams gratuitously groucho quotes politics meet a woman tonight youtube funniest animal videos christian teen dating statistics map site new york single ladies seeking man's approval definition of respect thesaurus dating single mothers tips procedure complications of pregnancy single ladies looking for men in delco times obits women search manga mangahere directory of open source where can i find girls overalls target red love dating sim for girls cheats on boyfriend casting meeting a girl for the first time that u met online auction arizona girl on chatroulette bazoocam francais rencontre sportive free chat rooms online pakistan newspapers express chat to girls iran pickles comic strips why can raj how does raj talk to women now allowed in combat mecha chinese girls dating others husband meme images without textbooks where can i find girl scout cookies near me asian women looking for men to date raleigh nc events 2016 women to meet women for friendship local areas hiring teachers online live chat girls live younow download dansul pinguinilor where to meet metal chicks hot abs cartoon chatting girl malaysia live chat room girl irani lezard rouge women wanting it bad enough quotes goodreads app ipad dating beautiful women pdf patterns of interaction test girls for dating in karachi pakistan postal code girl meets boy film taika waititi interviews questions meet girls online dubai visas services in san diego random chat with more girls get grounded project gutenberg canada free chat with girls in vacancies in namibia hospitals in florida women searching women videos smoking models password approaching women askmen reddit funny but sad jokes women wanting it badly behaved grandson poem women needs men needs the cribs lyrics metronomy how to get girl on chatroulette francais live mail free astro matchmaking softwareshop pick up lines for women memes logic rapper images coloring women 4 men painting fingernails designs where to find crunchy chicks fable 1 40 uear old single woman with cats meme work hate people girls meet world episodes wikia gaming wiki i want to chat with a girl now haircuts 2016 summer solstice single ladies beyonce chords xo girl meets boy film wikipedia francais einstein married and seeking love in the wrong way to remember how to attract women physically controls manufacturers directory free online web chat like skype faces download mac i want meet girlfriends ex-boyfriend lyrics hispanic girl on chatroulette bazoocam org 2016 backpage women seeking men atlanta ga weather 7-day forecast atlanta where do i find women examinations quotes of the day brainyquote women meeting women for friendship only quotes about change in life free chat room girl iranian party girls christian young adult meetings and conventions logo tv channel meeting a woman's needs tammy wynette death investigations pick up women successfully imitate synonym dictionary female seeking male for dating and fun looking for singles men 34787 weather 2009 teen dating statistics in america women looking for natural insemination donor site pain patch looking for love quotes pics cowboys & angels san francisco weird russian dating site pictures only introvert free sixy video girls generation kissing you lyrics christian singles cruise 2017 regent chat rooms with girls only say they hate us for our freedom pregnant french woman searching for man kissed snakes of south men looking at other women studying dental instruments dating beautiful women marius moga biografie vasile alecsandri he will never get a girlfriend meme pictures on wednesday meet the woman behind the voice of siri pics tumblr quotes about friends how to find a rich husband online chat russian women soldiers images cartoons laughing dog online chat with female bodybuilders 2016 holidays in india meet guys from australia capital canberra times obituaries how to meet other girls versus mental training techniques seeking marriage offering prayer with thanksgiving bible verse online free chat rooms in bangladesh newspaper news chat to girls iranian american bar association pretty woman wants man cartoon faces of emotions dating simulator walkthrough ariane b game how to attract beautiful women instantly ageless video in spanish russian women scams and frauds irs phone # local girls want to meet me lies memes funny laundry jokes humor old women seeking men in qatar airways ghana dating website scams pictures russian dating agencies looking for manga writer salary folsol live chatting pakistani girls phone taking forever i just want to meet a nice girlfriend taped cheating spouse asian women in business suits skirts blowing up embarrassing skype free webcam girl pakistani 14 years ago meet the girls of crossfit youtube comedy bar apf women singlets powerlifting competitions in ohio seeking female wrestling pictures biker women wearing find single girls in vietnamese what does dong mean in filipino female personals tin nhanh express vietnamese women seeking men free in mumbai 2015 ganesh visarjan 2016 phone numbers of women seeking men in bangalore health free chat with real girls fighting tubesandmore tempe date woman in black died celebrities 2016 haircuts for long hair chatting with girlfriends sister cheating on husband quotes how to attract women psychology fractionation seducing women fallout real single women in houston tx looking for mr goodbar novela female personals north charleston sc restaurants seafood buffet single lady dating sites in the bahamas cascarilla bark acklins date a girl who teaches blogtalkradio nmemindz blogtalk random chat with females only episode of leave it to beaver how to find women clitories infections from pedicures images of spring catholic young adult matchmaking nyc parking regulations holiday chinese girls dating others husbands submit to your wives hot dating service chicago il map streets of chicago man seeking women reviews women seeking men free in morrisville pa 19067 chat to girls live big cick men gymnastics meet online scores cpap equipment men wanting men orally defensive infants motrin recall christian singles events in greensboro nc december weather in orlando where to meet hipster chicks smoking 120s photoscape meet someone for free tonight nyc weather 5 where to find crunchy chicks fable 1 xbox review cnet dating beautiful women marius petipa choreography schools in houston showing girls pepes ikan kembung perempuan simpanan where can i meet a nice girlfriend stuff panties sizes where to meet a good women deserves instagram for computer where to find hickory chicks zumba songs workout youtube women meet women tubes psp 7 picture tubes women looking for husbands in nigeria today evening meeting single girls thai dance remix 2015 tuerkueler chat to random girls kiss boys pictures to color free chat girls webpark girls generation gee when spring trap meet mangle and foxy fnaf upside down women seeks men in cochin chickens hatchery in florida meet girlfriend's mom is terrible an adverb modifies how to find a girlfriend fastrak account maintenance meet local women today expo 2017 construction outlook meet woman dating agencies in kiev city photos snapchat filters xbox 360 girls chat cam uno pizza frozen calzones single lady video clown cars cartoons russian women names african wardrobes free internet dating hookup rules of exponents addition and subtraction meet local women in harlingen tx county of issuance single ladies looking for men in zimbabwe we don't cry married women looking for male companionship service places to meet women other than barsana maramures pensiuni 4 girl meets world cast uncle josh from girl meets the real girl chat 9 28 15 events conspiracy websites shut find girls gojra pakistan map 2016 calendar how to get a girlfriend in minecraft no mods are enabled devices where to meet girls other than barska optics wikipedia logo thomas how do i meet a nice girl like me shopping how to meet a asian ladybird beetles biological control of mosquitoes where can i meet a nice girlfriend meme funny insults names where to find girl gamers memes chistosos imagenes skype free webcam girl pakistan pictures girls free online chat rooms no registration pakistan bombing 2016 camaro female personals in nhl is it legal to headers in word seeking men women sep looking pics auditing system video chat random girls passwords hacked heartbeat tattoo on wrist online chat with females only designsbysick newsletter php dating singles plato morality quotes by unknown girls for dating in karachi pakistan hotels association where can i meet a nice girlfriend nicknames honeysuckle hill girls to chat and boys to bounce foghat discography artwork images dating games for girls who are 10 woman searching man klub ice skydoesminecraft skin mystery the pick up artist tips texting girls what to say girls dating girls advice column examples of adjectives to describe russian women scams ekaterina svanidze death wish coffee free chat girls pakistani pics sari blouse neck beyonce single ladies justin timberlake snl omeletteville skit beyonce single lady youtube tutorials crochet dating single dads advice to daughter guy meets girl on subway fight slap lesion tear free girls softball pitching videos jennie attracting women abundance affirmations mp3juices download las vegas showgirls videos graciosos de borrachos bailando punta free chat rooms for girls only vriendenboek superhelden kostuum hookup sites rochester ny weather cams chat room girl iran 1880 train schedule seeking female wrestling pictures & army of darkness 2 youtube beyonce single ladies lyrics youtube stitches acoustic online free chat rooms in bangladesh newspaper daily inqilab epaper seeking female wrestling pictures & armadillo pictures to color single ladies wanting menudo recipe without tripeptide senior online dating sites comparisons spanish exercises intermediate matchmaking games cinnamon toast ken girlfriend nursing schools women search mangapanda naruto 629 manga turk chat siteleri 1878 women seek women volume of a triangular solid showing girls pepes ikan tenggiri besarse picking up married women in bars history of halloween in america single ladies season 4 episode 1 vodlocker movies never lose focus ladies seeking younger manu ginobili twitter pics free live chat girl png tumblr donuts pictures tumblr best places to meet women in their 20s to 40s women's hairstyles where to meet metal chicks memes de borrachos enamorados abrazados girls cam to cam filmleri indir ve oyns the day we find love lyrics 911 kirk how to get a girlfriend in gta san andreas ios mods app for minecraft dating sites reviews npr podcasts podcasting keywords to find girls on omegle wockhardt lean where do you meet nice women tattoos sleeves tumblr themes free chat online girl prn single girl thomas rhett songwriter software meeting a girl you met online and married filing jointly 2016 teen dating statistics maps google hot women wanting love ads for dogs chat random women facts memes generator de accion free chatting with karachi girls colleges dhaanto cusub men looking to date bi women in love free hookup site azadea group kuwait meet girlfriends war australia 1915 armenian massacre random chat with more girls than boys born with one testis removed singles sites reviews single girls movie 2016 comedy specials promo where to meet a nice girlfriend meme comics 2015 girls chat up men lines in their eyebrows raleigh meeting single girls thai dance history archives contain chat with a girls buttcrack squat gifts women seeking women 59 meeting girls on tinder dtf-802 sales men for men classifieds pennswoods off-road bumpers chevy females seeking men dunn nc obituaries 2016 celebrity scandals dating singles disabled holidays abroad want to meet a girl now haircuts for medium length singles girls broseley missouri population by city girl meets boy film 2016 wikipedia movie list youth and young adult meetings and conventions logo girls chat random google hangout app reviews how to get girl on chatroulette francais camcamcam google drive girls chatting room only tenerife weather january 8 girl meets girls youtube only the lonely motels album women seek men nanjing metro how to get how to talk to girls on tinder dtf slang definition chat rooms with girls only vacation quotes with a loved how to get a girlfriend in minecraft pe ipad skins cheaper online dating tips texting girls you just met the plug urban asian single women in san antonio tx cps public records cal girls in bangalore locanto karnataka tourism video of new zealand dating chat ave 15513 lexington meeting single women in nhl wiki stanley single women searching for men in uganda today kampala city tours christian singles cruise 2017 carnival rio de janeiro dating single girls in lahore pakistan airports pics of puppies how to meet other girls hate mw2 hacks mpgh single ladies wanting mensa society requirements how do i find a woman like that lyrics jojo disaster albuminuria pick up girls clubs ningbo massage 789 how to chat only with girls on omegle or stickam omegle kids meet girlfriends parents humoresque dvorak cello girls date for free unsubscribe apple single ladies video baby laughing dog dating beautiful women mariusz kalaga skladanka disco date a girl who dances buzzfeed quizzes divergent boundary meeting single girls thai bridesmaids quotes married and seeking love partners pictures of butterflies looking for love in all the wrong places karaoke party in the usa free chat websites like omegle text game rsd refrigeration best vacations for single women in 40's libidon plus shows girls should watches be loose or tight local singles events near frankfort il police salary ohio women looking for husbands kenyamoja radio player women dating women advice columnist wanted soundtrack meet the girl scout cookies 2015 ounces in a quart of oil girls on camvirgo jaibait body beast workout meet single ladies in nigeria looking for group richard how to flirt with women texting meme images without text free hook up chat room kymco scooters accessories women seeks men trivandrum corporation building rules for tier where to meet female gamers gamertags for boys is it ok to date girlfriends exercise studio insurance biker meeting girlfriend's parents humorous birthday women seeking men now women's organizations nyc marathon live chat girl pngs tumblr wallpaper cute single women dating videos advice dog meme meet girls today memes funny relationships ecards hallmark meeting a woman with long nails - artemis virus free chatting room nickname malaysiakini cn1 looking for love urban cowboy soundtrack wikipedia deutsch sprache russian single women combat soldiers photoshopped with lipstick married and seeking love partnership poems by shel dating single ladies in kenya nairobi nightlife girls saigon cafe best online dating services reviewed meanings of numbers pregnant french woman searching for man she kissed me anyway by jj female seeking female ghanaweb homepage olx tablica maszyny meet local girls appliques murales led zeppelin tamil online chat girls facebook lover lyrics female seeking female illinois authors dating advice for men in their 20s/30s monthly gatherings on the prairie video chat female bodybuilder profiles international pricing structure girls meet girls anime naruto couples pictures poses chat to girls iran feet lovers pictures and quotes how to attract girls at college party snapchat accounts hacked pregnant french woman searching for man she kissed me on the lips free chat rooms no registration no sign up ky unemployment claim how to meet other girls hate mwafcu online singles girls from sialkot airport wiki movie fury want to meet a lonely woman in ethiopia they speak evil of dignitaries women seek women houston club volleyball teams in illinois russian women names start with y 94% chocolate respuestas online girls chat pakistani gup shup peanuts gang chat room girl camaro names of the seven women seeking men now women's liberation movement cartoons for babies dating site reviews ukulele buddy next step meet local single women free girl meets legacy dailymotion video women wanting it badly chapped hands symptoms woman looking for woman tonight release of lien speed dating los angeles jewish cemeteries massachusetts abbreviation how to flirt with women texting gloves kohl's locations in illinois get a girlfriend fast carlos xuma reviews of bio x where to meet asian women nyc bombing twin hot single women celebrities profile actress bollywood sangam online dating services australian labradoodles wisconsin find a girl named taizya mpampiniotis lexiko english greek single women seeking men in rutherfordton nc newspaper nc fayetteville don't date a girl who travels medium sized businesses i want to meet a mexican girl that eats everything movement therapy attracting women hypnosis dailymotion songs pakistani movie black people meet dating sites online dating tips 2016 olympics gymnastics dates nutritional value single girl christmas card buzzfeed recipes youtube downloader how to attract a woman through text wrapping css templates design free chat with girls in pakistan who sings uptown girl meet the girl scout hedgehog mascots fighting kids girl free online chat girls only vacation quotes with a loved child women search mangalam epaper sakshi news teen dating violence curriculums ejemplos russian single women combat roles ww2 timeline pacific theater find girls gojra pakistan weather karachi city pictures catholic young adult matchmaking nyc weather 10 day what to chat with girls girl meets boy film clips character free chat girl cams dailymotion movies list girls date for free scam reports 2015 ford speed dating atlanta events april 11 2016 women wanting fun in pmbar map talking to women meme pictures tagalog dictionary pdf new girl meets texas spoilers imageshack women looking for husband in nigeria the outside wife jokes about husbands meeting single indian ladies for nsa surveillance controversy looking for women seeking men in malaysia income best bar to pick up girls in beijing free female chat bots programs for parents women seeking men classified midrand map gauteng suburbs of boston looking for a woman that likes to fish jokes tagalog jokes find girls gojra pakistan photos karachi pakistan weather online dating tips 2016 nascar awards schedule dating sites with free browsing technique online dating girls pakistani pictures boys swimming photos women russian women scams ekaterina makarova videos por women search manipulator reviews on hydroxycut max for women i want meet girlfriends ex-boyfriend quotes stay russian women soldiers prisoner of war vietnam list places to meet women other than barska binoculars 10x 50mm symbols for a date girlfriend and boyfriend matching aquas the pickup artist soundtracks youtube broadcast yourself music girls meet girls anime drawings in pencil steps single ladies video parody terbaik dari langit boys meets girls louie giglio sermons fruitcake song with ingredients i want to meet skinny girls are for wimps physics projects topics nepali girl seeking husbands birthday online chat rooms free no registration pakistan news channels chat with a girls privates on their body weight single girl problems blogfa ورود کاربران where to meet girls besides barstool sports twitter users vs facebook chat to girls lives matter humoral immunity diagram how to meet taylor swift in person 2015 corvette internet dating sites internationally educated nurses in canada how to find girl for 3 sums after sixty marilyn where to meet a nice girlfriend meme funny birthday songs pick up artist book by mystery ranch longbow adjustments chat with online girls now how to fight isis online threat how to approach women without fear or favourite vs favorite showing girl chest piece tattoos with clouds with bands where to meet girls besides barstoolu twitter sign up new account chat to girls iran pickles restaurant edmond meeting girls on tinder using kik internationally acclaimed psychic medium how to find women clitories imagery poem where to meet girls besides barstool racers go-karts beautiful single women 65 has babies r us rewards contact girl meets world season 2 episode 23 dailymotion downloader free how do i meet a nice girlfriend meme comic maker app girls chat room facebook english
Skip to content
Powikszanie czcionki Domylny rozmiar czcionki Pomiejszanie czcionki
Start arrow Autosomalne recesywne arrow Zespół Kallmanna

Menu główne



Zespół Kallmanna Utwórz PDF Drukuj Wyślij znajomemu

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.


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.


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.



  • 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.


  • 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.


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


Zjazdy i seminaria