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Horizon test

 

Igaüks meist kannab keskmiselt vähemalt kahte geneetilist haigust põhjustavat geeni. Haiguse kandjad on tavaliselt terved, kuid neil on märkimisväärne oht anda raske geneetiline haigus edasi oma lastele.

 

Horizon-test on geneetilise haiguse kandluse hindamise sõeltest, mis võimaldab määrata naisel ja/või tema partneril autosoom-retsessiivsete või X-liiteliste haiguse kandlust. Sellised geenimutatsioonid võivad nende ühistel lastel põhjustada 274 erinevat geenihaigust, mida pole sünnieelsel ultraheliuuringul ega ka vahetus sünnijärgses perioodis võimalik avastada, kuna enamik neid avaldub alles lapse esimestel eluaastatel.

 

 

Horizon-testi on soovitav teha eelistatult juba siis, kui pere planeerib rasedust, kuid antud testi saab teha ka raseduse esimeses trimestris.

 

 

 

 

Kuidas on võimalik, et terved vanemad pärandavad oma lastele edasi geneetilise haiguse?
 

On olemas kaks põhilist pärandumistüüpi, mis võib viia selleni, et terved vanemad saavad tõsise geneetilise haigusega lapse. Nendeks pärandumistüüpideks on autosomaalne retsessiivset tüüpi- ja X-liitelist tüüpi pärilikkus.

 

Mis on autosoom-retsessiivne pärilikkus?
 

Osa pärilikke haigusi pärandub retsessiivsel teel. See tähendab, et geneetilise haiguse avaldumiseks peab lapsel olema muutus mõlemas ühe geenipaari geenis (laps pärib ühe muutusega geenikoopia kummaltki vanemalt). Kui laps pärib oma vanemalt ühe muutustega geeni ja teise normaalse geeni, siis enamikel juhtudel normaalne geen korvab muutustega geeni. Siis on laps muutuse kandja, kuid ta ei ole haige.
 

Sagedasemad autosoom-retsessiivsed haigused on sirprakuline aneemia ja tsüstiline fibroos.

 

Kuidas retsessiivsed haigused päranduvad?
 

Kui mõlemad vanemad on sama geenimutatsiooni kandjad, siis annavad nad oma lapsele edasi kas normaalse või muutusega geeni. Valik toimub juhuslikult.

Seetõttu igal lapsel, kelle mõlemad vanemad kannavad ühesugust muutunud geeni, esineb 1 juhul 4-st risk (25%) saada mõlemalt vanemalt mutatsiooniga geen ning seetõttu haigestuda pärilikku haigusesse. Samuti esineb 3 juhul 4-st (75%) võimalus, et laps ei ole päriliku haigusega.
 

Samas esineb 2 juhul 4-st (50%) võimalus, et laps pärib oma vanematelt ühe mutatsiooniga geeni. Sellisel juhul on laps küll terve, aga kandja nagu vanemadki. Aga 1 juhul 4-st (25%) esineb ka võimalus, et laps saab vanematelt kaks normaalset geeni. Sellisel juhul lapsel ei esine geneetilist haigust ning ta ei ole ka selle geneetilise haiguse kandja.

 

Kuna autosomaal-retsessiivsete haiguste puhul paiknevad haigust põhjustavad geenid autosoomis (kromosoomid 1-22), siis avaldub haigus ühtmoodi nii poistel kui ka tüdrukutel. Sellised riskid esinevad iga raseduse puhul.

 

Mis on X-liiteline retsessiivne pärilikkus?

 

X-kromosoomis on mitmeid geene, mis on vajalikud kasvamiseks ja arenguks. Y-kromosoom on palju väiksem ja selles on ka vähem geene. Naistel on kaks X-kromosoomi (XX) ja kui ühes X-kromosoomis on muutus, siis normaalne geen teises X-kromosoomis võib muutused kompenseerida. Sellisel juhul on tüdruk väliselt terve X-liitelise haiguse kandja. Haiguse kandjad naised ei ole haiged, kuid kannavad endas muutustega geeni. Mõne sellise haiguse puhul on naistel haiguse kulg kergem.

Poistel on X- ja Y-kromosoomid (XY) ning juhul, kui üks geen X-kromosoomis on muutustega, neil teist, kompenseerivat geeni ei esine. Seetõttu on poiss haige. Selliselt päranduvaid seisundeid kutsutakse X-liitelisteks retsessiivseteks haigusteks.

 

Sagedamini esinevad X-liitelised haigused on hemofiilia A, Duchenni lihasdüstroofia ja fragiilne X sündroom.

 

Kuidas X-liitelised haigused naissoost kandjate kaudu päranduvad?

 

Kui naissoost kandjal sünnib poeg, siis ta annab oma pojale kas normaalse geeniga X-kromosoomi või X-kromosoomi, milles on muutusega geen. Kõikidel kandja ema poegadel on seetõttu 1 juhul 2-st (50%) tõenäosus saada mutatsiooniga geen ja olla haige. Samas esineb ka 1 juhul 2-st (50%), et poeg saab normaalse geeni ega ole haige. Selline pärandumismuster kehtib kõikide poegade kohta.

Kui naissoost kandjal on tütar, siis ta annab oma tütrele edasi X-kromosoomi, kus on normaalne geen, või X-kromosoomi, milles on muutusega geen. Kõikidel tütardel on 1 juhul 2-st (50%) võimalus saada mutatsiooniga geen. Kui see juhtub, siis on tütar muutuste kandja nagu emagi. Samas esineb ka 1 juht 2-st (50%) võimalus, et tütrele pärandub normaalne geen. Sellisel juhul tütar ei ole kandja ja seda haigust tal ei ole. Selline pärandusmuster kehtib kõikide tütarde kohta.

Kas minu lapsel on risk nende haiguste suhtes, kui mida meie suguvõsas ei esine?

 

Jah, on küll. Reeglina sünnivadki uuritavate haigustega lapsed perre, kus varem ei ole haigust esinenud. See risk püsib ka siis, kui vanematel on sündinud ühised terved lapsed. Seega on haige lapse sünd perre sageli ootamatu. Eestis kinnitub igal aastal keskmiselt 13–15 lapsel sõelutav haigus.

 

Kas otsitud haiguseid on võimalik diagnoosida juba sünnieelselt ultraheliuuringul?

 

Pärilikke geenihaigusi haigusi ei ole võimalik sünnieelselt ultraheliuuringul tuvastada ning neid haigusi ei ole seostatud ka raseduse-või sünnitusaegsete probleemidega. Ka pärast sündi ja esimestel elunädalatel näib enamik neist beebidest terved. Haigus ilmneb hiljem tavaliselt esimese eluaasta jooksul.

 

Kui sageli need geneetilised seisundid esinevad?

 

Lapse tervist võib mõjutada sadu pärilikke geneetilisi haigusi, kuid enamik neist on väga haruldased.

Kui aga arvesse võtta kõikide selliste haiguste esinemissagedus, tabavad need harvikhaigused 1 last 400-st.

Enamikul paaridest, kellel on haigestunud laps, pole antud haigust suguvõsas esinenud ja nad pole olnud teadlikud, et neil on suurem võimalus saada geneetiliselt haige laps. See juhtub seetõttu, et terve paar võib oma lapsele geneetilist haigust edasi anda, teadmata, et nad on selle haiguse kandjad. Seetõttu on geneetiliste haiguste kandluse sõeluuring oluline kõigile, olenemata sellest, kas nende perekonnas on olnud geneetilisi haigusi põdevaid sugulasi või mitte.

 

Mis on Horizon-testi alternatiivid?

 

Horizon-test on lapsevanemate sõeltest autosoom-retsessiivsete või X-liiteliste haiguste kandluse

avastamiseks. Sellega on võimalik tuvastada 274 geneetilise haiguse risk, mida vanemad võivad teadmatult oma lapsele edasi anda.

 

Horizon-testiga ei ole võimalik tuvastada loote kromosoomihaigusi, mikrodeletsioone, monogeenseid haigusi ega sugu. Horizon testiga pole võimalik hinnata ka loote anatoomilisi struktuure ega rasedusega kaasneda võivaid tüsistusi nagu preeklampsia. Kui soovite teavet ka loote kromosoomipatoloogiate, mikrodeletsioonide, monogeensete haiguste, loote organstruktuuride arengu ja rasedusaegsete komplikatsioonide kohta, on võimalik Horizon-testi kombineerida PanoramaXP testi, Vistara testi ja OSCAR testiga.

 

Naiste puhul, kelle ultraheliuuringus tekkib loote arengurikke kahtlus, on kasutusel sellised invasiivsed diagnostilised testid nagu koorionbiopsia või looteveeuuring, mis tuvastavad üle 99% kõigist kromosoomianomaaliatest, sealhulgas ka haruldasi kromosoomianomaaliaid, mida Horizon-testi ega ka teiste sõeltestidega avastada ei saa. Diagnostiliste uuringute korral tuleb ainult arvestada sellega, et 0,1%-l juhtudest võivad need põhjustada raseduse katkemise sõltumata sellest, kas loode oli kromosomaalse või geneetilise patoloogiaga või mitte.

 

Millal ma oma testi tulemused teada saan?

 

Testi tulemused saad teada 21 päeva möödudes pärast vereanalüüside andmist.

 

Milliseid tulemusi ma Horizon-testist oodata võin?

 

Naisena annab Horizon-test Sulle informatsiooni, kas Sa kannad ühte 274-st autosomaal-retsessiivsest või X-liitelisest haigusest. Kui oled mees, siis annab Horizon-test Sulle informatsiooni, kas Sa kannad ühte 254-st autosomaal-retsessiivsest haigusest. Mehi ei uurita X-liiteliste haiguste suhtes.

 

Negatiivne testi tulemus oluliselt vähendab võimalust, et oled geneetilise haiguse kandja, kuid Sa peate olema teadlik, et Horizon-test ei avasta kõiki geenihaigusi.

 

Kas positiivne sõeluuring tähendab, et lapsel on uuritav haigus?

Ei tähenda. Horizon-test uurib lapsevanemaid, mitte emaüsas kasvavat loodet. Kui mõlemad vanemad kannavad defektset geeni, siis on 25% juhtudest oht, et laps on haige. Sellise vastuse korral on vaja konsulteerida meditsiinigeneetikuga ning selleks, et kinnitada või välistada lootel geenihaiguse olemasolu, tuleb naisel teha diagnostiline test, näiteks koorionbiopsia või looteveeuuring või sünnijärgselt vastsündinu veeniverest teostatav diagnostiline uuring.

 

Mida me saame teha, kui meil on suurem tõenäosus saada geneetilise haigusega laps?

 

Kui te enne rasestumist saite teada, et Sina ja Su partner kannate sama autosomaalset retsessiivset geneetilist haigust või Sa ise oled X-liitelise haiguse kandja, siis on võimalik:

 

  • loomulik rasestumine ja lapse testimine pärast sünnitust;
  • loomulik rasestumine ja raseduse ajal koorionbiopsia teostamine loote geneetilise haiguse avastamiseks;
  • kehaväline viljastamine (IVF) ja embrüote siirdamiseelne testimine monogeensete haiguste suhtes (PGT-M), et emakasse siirdada geneetiliselt terve embrüo;
  • kehaväline viljastamine, kasutades geneetiliselt terve doonori spermat, munarakke või embrüot;
  • lapsendamine;
  • loobuda lapsesaamise plaanist;
  • X-liitelise retsesiivse haiguse kandluse puhul on soovitatav teha Panorama test loote soo hindamiseks, sest haigestuvad ainult poisid. Tüdrukloote puhul pole vaja teha täiendavaid diagnostilisi uuringuid.

 

Kui saite teada raseduse ajal, et Sina ja Su partner kannate sama geneetilist haigust või Sa ise oled X-liitelise haiguse kandja, siis on võimalik:

  • diagnostiline koorionbiopsia loote geneetilise haiguse avastamiseks.
     

Haige lapse puhul on teil õigus otsustada, kas rasedus katkestada või seda jätkata. Raseduse jätkamise puhul saate ennast emotsionaalselt ette valmistada haige lapse sünniks.

 

Mida teha siis, kui olen geneetilise haiguse-või X-liitelise haiguse kandja?

Sellisel juhul võiks sellest rääkida ka teiste pereliikmetega. Siis on neil soovi korral võimalus teha Horizon-test, et välja selgitada, kas ka nemad on geneetilise haiguse kandjad. See informatsioon võib

olla vajalik teistel pereliikmetel esineva haiguse diagnoosimisel. Eriti oluline võib see olla nende jaoks, kellel juba on lapsed või kes tulevikus plaanivad lapsi saada.

 

Keda saab testida ja millal?

 

Autosomaal-retsessiivsete haiguste avastamiseks teostatakse Horizon-test mõlemal partneril. X-liiteliste haiguste avastamiseks piisab, kui testi teeb ainult naine. Horizon-testi tuleks eelistatult teha enne rasestumist, samas saab testi teha ka raseduse esimesel trimestril.

 

Kuidas Horizon-testi teostatakse?

 

Horizon-testi tarbeks on vajalik mõlema partneri veeniveri, mis suunatakse San Carlose Natera

laborisse DNA eraldamiseks ning teise põlvkonna sekveneerimiseks.

 

Kes saab Horizon-testi tegemisest kasu?

  • Terved tulevased vanemad, kes planeerivad rasedust või on raseduse varajases staadiumis
  • Teatud etnilise taustaga või sugulusabielus olevad paarid, kelle geneetilise haiguse risk võib olla suurem
  • Rasedust planeeriv paar, kui ühel või mõlemal on esinenud suguvõsas vaimse alaarenguga või geneetiliste haigustega sugulasi

 

Milliseid geneetilisi haigusi võib leida, kui ma teen Horizon-testi?

 

Autosoomretsessiivselt päranduvad haigused (254 haigust)

 

  • 3-Beta-hüdroksüsteroiddehüdrogenaasi II tüübi puudulikkus (HSD3B2)

    What is 3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency?

    3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency is an autosomal recessive condition.  It is one of a group of inherited disorders called Congenital Adrenal Hyperplasia that affect the hormones made by the ovaries, testes, and adrenal glands.  People with 3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency do not make enough of certain hormones needed by the body. There are three forms of this condition: salt-wasting, non-salt-wasting, and non-classical.  Babies with the salt-wasting form have symptoms that start shortly after birth and include poor feeding, vomiting, and dehydration which can lead to death if not treated. People with the non-salt-wasting and non-classical forms do not have these symptoms.  All three forms result in decreased amounts of sex hormones. This leads to abnormal development of the genitals in males which sometimes results in external genitals that look female instead of male (ambiguous genitalia).  Without treatment, both males and females with this condition do not go through normal puberty and often cannot have their own children. Without treatment, high blood pressure and low potassium levels are also common.  People with the non-classical form of the condition have symptoms that are typically milder than the other two forms. Treatment includes hormone replacement therapies and sometimes other supplements or medications.

     

    What causes 3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency?

    3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency is caused by a gene change, or mutation, in both copies of the HSD3B2 gene pair. These mutations cause the genes to not work properly or not work at all. When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates 34%; Residual risk 1 in 757

  • 3-hüdroksü-3-metüülglutarüül-CoA lüaasi puudulikkus (HMGCL)

    What is 3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Deficiency?

    3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) Lyase Deficiency is an autosomal recessive condition.  It is one of a group of inherited disorders known as Organic Acid Disorders.  People with HMG-CoA Lyase Deficiency cannot break down leucine, one of the building blocks of protein, and cannot use body fat as energy.  Signs and symptoms often start in infancy or early childhood and include lack of energy, poor feeding, poor muscle tone, diarrhoea, vomiting, low blood sugar (hypoglycemia), breathing problems, seizures, and coma, which, if left untreated, can lead to death.  Episodes of low blood sugar and metabolic acidosis, where toxic substances build up in the blood, can be triggered by going a long time without food (fasting), illness, or eating large amounts of protein.  If the condition is not treated, repeated episodes of metabolic acidosis can lead to an enlarged heart and liver, vision and hearing loss, and intellectual disability.  Symptoms vary from person to person and some people never show symptoms.  Treatment includes a medical diet low in protein and fat, other supplements and medications, and avoidance of fasting.  If treatment is started early, people with this condition can often live healthy lives.  However, even with careful treatment, some children still have repeated episodes of metabolic acidosis and low blood sugar.

     

    What causes 3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Deficiency?

    HMG-CoA Lyase Deficiency is caused by a gene change, or mutation, in both copies of the HMGCL gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates 54%; Residual risk 1 in 1086

  • 3-metüülkrotonüül-CoA karboksülaas 1 puudulikkus (MCCC1)

    What is 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency?

    3-Methylcrotonyl-CoA Carboxylase 1 Deficiency is an autosomal recessive condition.  It is one of a group of inherited disorders known as Organic Acid Disorders.  People with 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency cannot break down a building block of a protein called leucine.  When food containing leucine is eaten, harmful substances build up in the blood causing repeated episodes of metabolic acidosis.  These episodes may include vomiting, lack of energy, muscle weakness, sleep disturbances, breathing problems, low blood sugar (hypoglycemia), seizures, coma, and sometimes even death.  These episodes are often triggered by eating large amounts of protein, going a long time without food (fasting), or illness. If not treated, this condition can lead to developmental delays and intellectual disability, poor growth, muscle problems, and liver failure. Symptoms can range from mild to severe and often begin in infancy or childhood, although some people do not have symptoms until adulthood and others never show symptoms. Treatment for children with 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency who show symptoms includes a medical low-protein diet and specific supplements. Treatment can prevent or lessen the symptoms in most people with this condition although some still have repeated episodes of metabolic acidosis even with careful treatment.   

     

    What causes 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency?

    3-Methylcrotonyl-CoA Carboxylase 1 Deficiency is caused by a gene change, or mutation, in both copies of the MCCC1 gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates 1 in 137; Detection rates 53%; Residual risk 1 in 290

  • 3-metüülkrotonüül-CoA karboksülaas 2 puudulikkus (MCCC2)

    What is 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency?

    3-Methylcrotonyl-CoA Carboxylase 2 Deficiency is an autosomal recessive condition.  It is one of a group of inherited disorders known as Organic Acid Disorders.  People with 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency cannot break down a building block of a protein called leucine.  When food containing leucine is eaten, harmful substances build up in the blood causing repeated episodes of metabolic acidosis.  These episodes may include vomiting, lack of energy, muscle weakness, sleep disturbances, breathing problems, low blood sugar (hypoglycemia), seizures, coma, and sometimes even death.  These episodes are often triggered by eating large amounts of protein, going a long time without food (fasting), or illness. If not treated, this condition can lead to developmental delays and intellectual disability, poor growth, muscle problems, and liver failure. Symptoms can range from mild to severe and often begin in infancy or childhood, although some people do not have symptoms until adulthood and others never show symptoms. Treatment for children with 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency who show symptoms includes a medical low-protein diet and specific supplements. Treatment can prevent or lessen the symptoms in most people with this condition although some still have repeated episodes of metabolic acidosis even with careful treatment.   

     

    What causes 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency?

    3-Methylcrotonyl-CoA Carboxylase 2 Deficiency is caused by a gene change, or mutation, in both copies of the MCCC2 gene pair. These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work properly, it leads to the symptoms described above.

     

    Carrier rates 1 in 120; Detection rates 54%; Residual risk 1 in 260

     

  • 3-fosfoglütseraadi dehüdrogenaasi puudulikkus (PHGDH)

    What is 3-Phosphoglycerate Dehydrogenase Deficiency?

    3-Phosphoglycerate Dehydrogenase Deficiency is an autosomal recessive disorder that affects the brain and nervous system.  Signs and symptoms usually begin infancy and include small head size (microcephaly), developmental delays, growth delay, intellectual disability, and seizures.  The brain develops abnormally and over time there is loss of brain tissue.  Affected infants may not achieve developmental milestones such as speech or sitting up without assistance.  In rare cases, symptoms do not begin until childhood or adulthood.  Currently, there is no cure for this condition; however, amino acid therapy may reduce seizures and other symptoms if treatment is started early in life.   

     

    What causes 3-Phosphoglycerate Dehydrogenase Deficiency?

    3-Phosphoglycerate Dehydrogenase Deficiency is caused by a change, or mutation, in both copies of the PHGDH gene pair.  These mutations cause the genes to not work properly or not work at all.  The normal function of the PHGDH genes is important for the development and function of the brain and spinal cord (central nervous system). When both copies of the PHGDH gene pair do not work correctly it leads to the symptoms described above. 

     

    Carrier rates < 1 in 500; Detection rates 95%; Residual risk 1 in 9041

  • 6-pürovoüültetrahüdropteriini süntetaasi puudulikkus (PTS)

    What is 6-Pyruvoyl-Tetrahydropterin Synthase (PTPS) Deficiency?

    6-Pyruvoyl-Tetrahydropterin Synthase (PTPS) Deficiency is an autosomal recessive disorder in which the body cannot break down a specific building block of a protein called phenylalanine. Phenylalanine is the most protein found in the diet and, if it cannot be broken down, it builds up in the blood and causes damage to the brain and nervous system. If untreated, symptoms of PTPS Deficiency usually begin shortly after birth and include seizures, abnormal muscle tone, unusual movements, and intellectual disability. Early treatment with a special medical low-phenylalanine diet and other supplements can often prevent or lessen the severity of symptoms.  

     

    What causes 6-Pyruvoyl-Tetrahydropterin Synthase (PTPS) Deficiency?

    6-Pyruvoyl-Tetrahydropterin Synthase (PTPS) Deficiency is caused by a gene change, or mutation, in both copies of the PTS gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates 59%; Residual risk 1 in 1218

  • Abeetalipoproteineemia (MTTP)

    What is Abetalipoproteinemia?

    Abetalipoproteinemia is a rare autosomal recessive disorder that prevents the body from completely absorbing certain dietary fats and the essential vitamins A, D, E, and K. Signs and symptoms of Abetalipoproteinemia usually begin in infancy but may first appear later in childhood, or rarely, not until adulthood. Symptoms include poor weight gain and diarrhoea along with abnormally shaped red blood cells (acanthocytosis). Affected children often have problems with balance, coordination, and walking due to problems with nerve function and muscle weakness. Anaemia and a type of vision loss called Retinitis Pigmentosa may also occur.  Treatment to attempt to slow down the progression of symptoms includes supplementation with the fat-soluble vitamins and other supplements along with a special low-fat medical diet. 

     

    What causes Abetalipoproteinemia?

    Abetalipoproteinemia is caused by a gene change, or mutation, in both copies of the MTTP gene pair. These mutations cause the genes to not work properly or not work at all.  The MTTP genes are important in helping the body absorb fats, cholesterol, and fat-soluble vitamins from the diet.  When both copies of the MTTP gene pair do not work correctly, it leads to the symptoms described above. 

     

    Carrier rates < 1 in 500; Detection rates 22%; Residual risk 1 in 641

  • Akondrogenees, tüüp 1B (SLC26A2)

    What is Achondrogenesis, Type 1B?

    Achondrogenesis, Type 1B is an autosomal recessive disorder that affects cartilage and bone. Signs and symptoms of this disorder include abnormal bone and joint development, a small rib cage that may cause breathing problems in the newborn period, short stature, short arms and legs, curvature of the spine (scoliosis), painful joints that restrict movement and early arthritis that worsens over time. Bone and cartilage abnormalities may also occur in the hands, feet, outer portions of the ears, head, and face. Intelligence is not affected. Currently, there is no cure or specific treatment for Achondrogenesis, Type IB.

     

    Three other related but less common inherited disorders are sometimes caused by specific mutations in the same gene. Diastrophic Dysplasia includes short stature, joint restrictions (contractures), cleft palate and other minor features. Atelosteogenesis Type 2 has symptoms similar to Diastrophic Dysplasia but is fatal in the newborn period. Recessive Multiple Epiphyseal Dysplasia includes short stature, joint pain, the curvature of the spine, abnormalities of the hands, feet, and knees, and sometimes other birth defects.  

     

    What causes Achondrogenesis, Type 1B?

    Achondrogenesis, Type 1B is caused by a gene change, or mutation, in both copies of the SLC26A2 gene pair. These mutations cause the genes to not work properly or not work at all. When both copies of this gene do not work properly, it leads to the symptoms described above. 

     

    Carrier rates < 1 in 158; Detection rates 93%; Residual risk 1 in 2244

  • Akromatopsia (CNGB3)

    What is Achromatopsia, CNGB3-Related?

    Achromatopsia, CNGB3-Related is an autosomal recessive condition that causes a partial or complete loss of colour vision.  Most people with this condition have complete Achromatopsia and can only see in shades of black, white, and gray.  Other vision problems seen with Achromatopsia, CNGB3-Related include light sensitivity, reduced sharpness of vision, involuntary shaking movements of the eye (nystagmus), farsightedness or, less commonly, nearsightedness. It is common for light sensitivity and nystagmus to appear within the first few weeks or months of life, although this may improve slightly over time.  Achromatopsia, CNGB3-Related is not the same as colourblindness, a condition where colour can be seen but it is difficult to distinguish between certain colours. Currently, there is no cure for this condition. Although rare, some individuals will have incomplete Achromatopsia with the ability to perceive some colour. Also rare is another form of the disorder called Progressive Cone Dystrophy where the loss of colour doesn’t begin until childhood or teenage years.

     

    What causes Achromatopsia, CNGB3-Related?

    Achromatopsia, CNGB3-Related is caused by mutations in both copies of the CNGB3 gene pair. These mutations cause the CNGB3 genes to not work properly or not work at all.  When both copies of the CNGB3 gene pair do not work correctly, it causes the symptoms described above. 

     

    Carrier rates < 1 in 98; Detection rates 925%; Residual risk 1 in 1214

  • Enteropaatiline akrodermatiit (SLC39A4)

    What is Acrodermatitis Enteropathica?

    Acrodermatitis Enteropathica is an autosomal recessive disorder that causes a deficiency of zinc in the body. People with this condition cannot absorb zinc from food.  If the condition is not treated, symptoms appear in infancy and include irritability, diarrhoea, hair loss, poor growth, abnormal nails, recurrent infections, and irritation of the skin called dermatitis. The skin problems, which include dry scaly skin and pimple-like lesions that may blister, occur most often around the mouth and anus. Psychological and neurological problems may also occur. Treatment with zinc supplements can prevent or improve symptoms. People with this condition who are treated can often live healthy lives.  Without treatment, this condition can be fatal.

     

    What causes Acrodermatitis Enteropathica?

    Acrodermatitis Enteropathica is caused by a gene change, or mutation, in both copies of the SLC39A4 gene pair.  These mutations cause the genes to not work properly or not work at all.  The normal function of the SLC39A4 genes is necessary for the body to absorb zinc. When both copies of the SLC39A4 gene do not work correctly, the body is unable to absorb zinc which leads to the symptoms described above. 

     

    Carrier rates 1 in 354; Detection rates 40%; Residual risk 1 in 589

  • Age infantiilne maksapuudulikkus (TRMU)

    What is Acute Infantile Liver Failure, TRMU-Related?

    Acute Infantile Liver Failure, TRMU-Related is an autosomal recessive disorder that causes temporary life-threatening liver failure in infants. Signs and symptoms show up shortly after birth. Babies with this condition have problems with feeding, vomiting, irritability, jaundice, lethargy, a distended abdomen, and abnormal laboratory results showing acute liver failure. Although the condition can be fatal, with proper medical treatment most infants survive the acute episode of liver failure. Children who survive usually do not have any further episodes of liver failure and have normal growth and development.   

     

    What causes Acute Infantile Liver Failure, TRMU-Related?

    Acute Infantile Liver Failure, TRMU-Related is caused by a gene change, or mutation, in both copies of the TRMU gene pair. These mutations cause the genes to not work properly or not work at all. If both copies of the TRMU gene pair do not work correctly, it leads to the symptoms described above. 

     

    Carrier rates < 1 in 500; Detection rates 63%; Residual risk 1 in 1350

     

     

  • Atsetüül-CoA oksüdaas I puudulikkus (ACOX1)

    What is Acyl-CoA Oxidase I Deficiency?

    Acyl-CoA Oxidase I Deficiency is an autosomal recessive disorder that causes the buildup of certain fatty substances in the body.  This causes damage to the brain that worsens with time.  Babies with this condition typically have problems feeding and gaining weight, poor muscle tone, seizures, and a distinctive facial appearance.  Some babies have extra fingers or toes, and some have an enlarged liver.  Over time, the coating around the nerves (myelin) in the brain and body breaks down.  This leads to loss of milestones and skills starting around the age of two years and intellectual and physical disabilities that worsen over time.  Hearing and vision loss may also occur. Lifespan is shortened and many children with Acyl-CoA Oxidase I Deficiency do not survive past childhood. Currently, there is no cure for this condition.

     

    What causes Acyl-CoA Oxidase I Deficiency?

    Acyl-CoA Oxidase I Deficiency is caused by a gene change, or mutation, in both copies of the ACOX1 gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates 73%; Residual risk 1 in 1849

  • Aicardi-Goutières'i sündroom (SAMHD1)

    What is Aicardi-Goutières Syndrome?

    Aicardi-Goutières Syndrome is an autosomal recessive disorder that affects the brain, immune system, and skin. Symptoms often first appear in infancy and include severe irritability, poor feeding, vomiting, fever, and seizures.  Episodes of brain inflammation (encephalopathy) cause slowed brain growth and small head size (microcephaly), delayed development, loss of skills, and inability to walk.  Most children with Aicardi-Goutières Syndrome have severe intellectual disability, muscle stiffness (spasticity), involuntary muscle spasms called dystonia and abnormal eye movements. They may also have painful or itchy skin patches called chilblains on their fingers, toes and ears. Lifespan is shortened. Children with this condition often do not survive past childhood, although people with milder symptoms may live into adulthood.  Currently, there is no cure or specific treatment for this condition.

     

    What causes Aicardi-Goutières Syndrome?

    Aicardi-Goutières Syndrome is caused by a gene change, or mutation, in the SAMHD1 gene.  These mutations cause the gene to not work properly or not work at all.  When both copies of the SAMHD1 gene do not work correctly, an abnormal immune and inflammatory response in the brain and skin occurs and leads to the symptoms described above.  

     

    Carrier rates < 1 in 500; Detection rates 72%; Residual risk 1 in 1783

  • Alfa-mannosidoos (MAN2B1)

    What is Alpha-Mannosidosis?

    Alpha-Mannosidosis is an autosomal recessive disorder that causes a toxic buildup of certain types of sugars, called oligosaccharides, in the body.  There are mild and severe forms of Alpha-Mannosidosis with signs and symptoms typically beginning in infancy or later in childhood.  In rare cases, symptoms may not begin until adulthood.  Many parts of the body are affected leading to distinctive facial features, intellectual disability, developmental delays, bone abnormalities, movement problems, muscle weakness, joint problems, frequent infections, psychiatric problems, and hearing loss.  The condition worsens with time.  People with Alpha-Mannosidosis often require a wheelchair.  Death may occur in childhood; however, lifespan may be near normal in individuals with a milder form of the condition. In some cases, affected individuals have been treated with stem cell transplantation from cord blood or bone marrow. Couples at risk of having an affected child may consider cord blood banking, as siblings have a higher chance of being a match for stem cell transplantation than a non-related individual.

     

    What causes Alpha-Mannosidosis?

    Alpha-Mannosidosis is caused by a change, or mutation, in both copies of the MAN2B1 gene pair.  These mutations cause the genes to not work properly or not work at all.  The function of the MAN2B1 genesis is to create an enzyme that breaks down certain sugars and clears them from the body. When both copies of this gene pair do not work properly, it causes a buildup of specific sugars in the body causing cell damage in many organs. This leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates 42%; Residual risk 1 in 861

  • Alfa-talasseemia (HBA1/HBA2)

    What is Alpha-Thalassemia?

    Alpha-Thalassemia refers to a group of autosomal recessive inherited blood disorders that result in a reduction in the amount of haemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. A person with one of the Alpha-Thalassemia diseases has lifelong anaemia. Mild anaemia can lead to tiredness, irritability, dizziness, lightheadedness and a rapid heartbeat. Severe anaemia can be life-threatening and may require routine blood transfusions.  The most severe form is usually lethal during pregnancy or shortly after birth unless treatment is started during pregnancy. In some cases, affected individuals have been treated with stem cell transplantation from cord blood or bone marrow. Couples at risk of having an affected child may consider cord blood banking, as siblings have a higher chance of being a match for stem cell transplantation than a non-related individual.

    Carriers of Alpha-Thalassemia can sometimes have mild anaemia.

     

    What causes Alpha-Thalassemia?

    Haemoglobin is made of both alpha-globin and beta-globin proteins. There are four HBA genes (also called alpha-globin genes) that are responsible for making alpha-globin.  Alpha-Thalassemia occurs when three or more of these four HBA genes are missing or changed, or when a person has changes, or mutations, called Constant Spring mutations, in two of the four genes. The exact type of Alpha-Thalassemia a person has depends on how many of the HBA (alpha-globin) genes are not working. Some common types of Alpha-Thalassemia are:

     

    Haemoglobin H Disease: caused by three missings or changed alpha-globin genes. A person who has three missing or changed alpha globin genes has Hemoglobin H Disease. Haemoglobin H disease can be mild or severe. People with severe disease may have chronic anaemia, liver disease, and bone changes. Some people with Hemoglobin H Disease require frequent blood transfusions and other treatments.

     

    Haemoglobin H-Constant Spring Disease: caused by two missing alpha-globin genes and one Constant Spring mutation. A person with these gene findings has Hemoglobin H-Constant Spring Disease. This condition is usually more severe than Hemoglobin H Disease. A person with this condition typically has chronic anaemia, is more likely to need blood transfusions, has more frequent viral infections, and may have an enlarged spleen.

     

    Homozygous Constant Spring Disease: caused by two Constant Spring mutations. A person with Homozygous Constant Spring Disease has mild to severe anaemia and symptoms similar to those seen in Hemoglobin H Disease described above.

    Alpha-Thalassemia Major, also known as Hemoglobin Bart’s Disease: caused by four missings or changed alpha-globin genes. This results in very severe anaemia. Affected babies develop symptoms before birth and unless treatment is started during pregnancy these babies are usually either stillborn or do not survive the newborn period. Mothers pregnant with a fetus with Alpha-Thalassemia Major can develop health problems during pregnancy.

     

    Carrier rates 1 in 500; Detection rates 90%; Residual risk 1 in 4991

     

     

     

     

  • Alporti sündroom, COL4A3-seotud (COL4A3)

    What is Alport Syndrome, COL4A3-Related?

     

    Autosomal recessive Alport Syndrome, COL4A3-Related is an inherited disorder that affects the kidneys, eyes, and ears. This condition causes progressive loss of kidney function which leads to blood and protein in the urine. Over time, the kidneys no longer work properly and dialysis or kidney transplant is often needed, typically in early to late adulthood. Sensorineural hearing loss usually occurs in late childhood or early teens, but hearing aids are helpful.  Eye problems include increased risk for cataracts, abnormally shaped lenses, and wearing away of the cornea.  People with Alport syndrome often need glasses, but it is rare for them to have vision loss. 

     

    Autosomal dominant Alport Syndrome, COL4A3-Related is a less common form of this disorder caused by a mutation in the same gene.  People with the autosomal dominant form have less severe symptoms that progress more slowly.  Kidney disease and hearing loss may not occur until late adulthood and eye problems are rare. 

     

    What causes Alport Syndrome, COL4A3-Related?

     

    Autosomal recessive Alport Syndrome, COL4A3-Related is caused by a gene change, or mutation, in both copies of the COL4A3 gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms of autosomal recessive Alport Syndrome, COL4A3-Related described above. 

     

    In some cases of Alport Syndrome, COL4A3-Related is inherited in an autosomal dominant manner.  This means that a person who has a mutation in just one copy of the COL4A3 gene is affected with Alport Syndrome and has symptoms of Alport Syndrome. 

     

    Carrier rates 1 in 354; Detection rates 8%; Residual risk 1 in 385

  • Alporti sündroom, COL4A4-seotud (COL4A4)

    What is Alport Syndrome, COL4A4-Related?

     

    Autosomal recessive Alport Syndrome, COL4A4-Related is an inherited disorder that affects the kidneys, eyes, and ears. This condition causes progressive loss of kidney function which leads to blood and protein in the urine. Over time, the kidneys can no longer work properly and dialysis or kidney transplant is often needed, typically in early to late adulthood. Sensorineural hearing loss usually occurs in late childhood or early teens, but hearing aids are helpful.  Eye problems include increased risk for cataracts, abnormally shaped lenses, and wearing away of the cornea.  People with Alport Syndrome often need glasses, but it is rare for them to have vision loss. 

     

    Autosomal dominant Alport Syndrome, COL4A4-Related is a less common form of this disorder caused by a mutation in the same gene.  People with the autosomal dominant form have less severe symptoms that progress more slowly.  Kidney disease and hearing loss may not occur until late adulthood and eye problems are rare. 

     

    What causes Alport Syndrome, COL4A4-Related?

     

    Autosomal recessive Alport Syndrome, COL4A4-Related is caused by a gene change, or mutation, in both copies of the COL4A4 gene pair.  These mutations cause the genes to not work properly or not work at all.  When both copies of this gene do not work correctly, it leads to the symptoms of autosomal recessive Alport Syndrome, COL4A4-Related described above. 

     

    In some cases of Alport Syndrome, COL4A4-Related is inherited in an autosomal dominant manner.  This means that a person who has a mutation in just one copy of the COL4A4 gene is affected with Alport Syndrome and has symptoms of autosomal dominant Alport Syndrome. 

     

    Carrier rates 1 in 353; Detection rates 88%; Residual risk 1 in 2934

  • Alströmi sündroom (ALMS1)

    What is Alstrom Syndrome?

     

    Alstrom Syndrome is an autosomal recessive disorder that affects many parts of the body. Signs and symptoms vary from person to person and usually begin in infancy or childhood. Children with Alstrom Syndrome typically have vision and hearing loss that worsens with time. A type of heart disease called dilated cardiomyopathy develops in some. Diabetes, obesity, breathing problems, liver disease, kidney disease, and short stature are common. Intelligence is not affected. Adults may have progressive liver and kidney disease that can lead to the failure of these organs. Depending on the severity of symptoms, lifespan may be shortened. Currently, there is no cure for Alstrom Syndrome although treatment is available for some of the medical problems that occur with this disorder.

     

    What causes Alstrom Syndrome?

     

    Alstrom Syndrome is caused by a gene change, or mutation, in both copies of the ALMS1 gene pair. These mutations cause the genes to not work properly or not work at all. When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates 1 in 500; Detection rates 51%; Residual risk 1 in 1019

  • Andermanni sündroom (SLC12A6)

    What is Andermann Syndrome?

     

    Andermann Syndrome, also known as Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum, is an autosomal recessive disorder that affects the brain and nervous system. Symptoms usually begin shortly after birth and include poor muscle tone and weakness with loss of feeling in the arms and legs. Underdevelopment of the corpus callosum (the part of the brain that connects the left and right sides) is common and reflexes are either absent or abnormal. Intellectual disability ranges from mild to severe and some children have seizures. Delays in learning to walk are common and teenagers often lose the ability to walk and may need the use of a wheelchair. Teens may have episodes of depression, anxiety, or hallucinations. People with Andermann Syndrome often live into adulthood but lifespan is usually decreased. Currently, there is no cure or specific treatment for this condition.

     

    What causes Andermann Syndrome?

     

    Andermann syndrome is caused by a gene change, or mutation, in both copies of the SLC12A6 gene pair. These mutations cause the genes to not work properly or not work at all. When both copies of this gene do not work correctly, it leads to the symptoms described above.

     

    Carrier rates < 1 in 500; Detection rates >95%; Residual risk 1 in 9981

     

     

     

     

  • Argininosuktsinaadi lüaasi puudulikkus (ASL)

    What is Argininosuccinate Lyase Deficiency?

     

    Argininosuccinate Lyase Deficiency is an autosomal recessive disorder in which the body is unable to remove ammonia.  Too much ammonia in the body and blood causes damage to the body’s organs. 

    Symptoms of Argininosuccinate Lyase Deficiency most often begin in the first few days after birth. Some children with this condition may have a milder form in which symptoms begin in late infancy or early childhood.  Newborns with symptoms may have vomiting, lethargy, irritability, or poor appetite.  If untreated, symptoms may worsen to include seizures, difficulty staying warm, muscle weakness, breathing problems, swelling of the brain, coma, or death within the first few weeks of life.  For those with late infancy or childhood-onset disease, symptoms may include intellectual disability, behaviour problems, hyperactivity, enlarged liver or liver disease, poor growth, dry and brittle hair, small head size, avoidance of meat or other high protein foods, and/or episodes of high ammonia in the blood.  Without treatment, life-threatening problems such as difficulty breathing, swelling of the brain, and seizures may develop.

     

    What causes Argininosuccinate Lyase Deficiency?

     

    Argininosuccinate Lyase Deficiency is caused by changes, or mutations, in both copies of the ASL gene pair.  These mutations cause the genes to not work properly or not work at all.  The normal function of the ASL gene is necessary to help remove ammonia from the body.  When both copies of the ASL gene are not working correctly, ammonia builds up in the body and leads to the symptoms described above. 

     

    Carrier rates 1 in 274; Detection rates 42%; Residual risk 1 in 472

     

     

 

Autosoomretsesiivselt päranduvate haiguste nimekiri on valmimisel

 

X-liiteliselt päranduvad haigused (20 haigust)

 

  • Adrenoleukodüstroofia, X-liiteline (ABCD1)

    What is Adrenoleukodystrophy, X-Linked?

    Adrenoleukodystrophy (ALD), X-Linked is an X-linked inherited disorder found most often in boys that mainly affects the nervous system and the adrenal glands, the small organs located on top of each kidney. In this disorder, the fatty covering (called myelin) that protects the nerves in the brain and spinal cord starts to break down. This causes problems when the nerves send information to the brain. In addition, damage to the outer layer of the adrenal glands causes a lack of certain hormones. Lower amounts of these hormones may cause weakness, weight loss, skin changes, vomiting, and coma. It is more common for boys to be affected than girls. In some cases, individuals with Adrenoleukodystrophy, X-Linked have been treated with stem cell transplantation from cord blood or bone marrow. Couples at risk of having an affected child may consider cord blood banking, as siblings have a higher chance of being a match for stem cell transplantation than a non-related individual.

     

    There are three different types of ALD, X-Linked: a childhood cerebral form, and adrenomyeloneuropathy (AMN) type, and a form called Addison disease.

     

    Childhood Cerebral Form: Children with this type of ALD have learning and behaviour problems that usually begin between the age of 4 and 10 years. Other symptoms include vision problems, difficulty swallowing, and poor coordination, all of which worsen over time. In addition, the adrenal glands start working improperly, which can cause vomiting, weakness, or coma. This type of ALD can progress rapidly and lifespan is shortened.

     

    AMN Type: People with this type of ALD develop progressive stiffness and weakness in their legs, urinary and reproductive tract problems, and problems with behaviour and thinking starting in early adulthood or middle age. Most people with this type of ALD have adrenal glands that work improperly leading to vomiting, weakness, or coma. In some severely affected individuals, damage to the brain and nervous system leads to early death.

     

    Addison disease: The first symptoms of Addison disease are vomiting and weakness or coma caused by improperly working adrenal glands. Symptoms can begin anytime between childhood and adulthood. By middle age, most people have additional symptoms of ALD. 

    Although most female carriers have no symptoms, some carriers may develop mild symptoms of ALD, X-Linked.

     

    What causes Adrenoleukodystrophy, X-Linked?

    Adrenoleukodystrophy (ALD), X-Linked is caused by a change, or mutation, in the ABCD1 gene. This mutation causes the gene to not work properly or not work at all. People with ALD, X-Linked cannot break down certain fats called very long-chain fatty acids (VLCFAs). These fats build up in the body and can damage the adrenal glands and fatty covering around the nerves and brain and lead to the signs and symptoms of ALD, X-Linked. 

     

    Carrier rates < 1 in 500; Detection rates 47%; Residual risk 1 in 943

  • Alfa-talasseemia vaimse alaarengu sündroom (ATRX)

    What is Alpha-Thalassemia Intellectual Disability Syndrome?

    Alpha-Thalassemia Intellectual Disability (ATRX) Syndrome is a rare X-linked disorder that affects mainly boys. It causes significant intellectual disability and delays in all areas of development. Many boys with this condition speak few, if any, words and some are unable to walk on their own. Common features of this condition include a smaller than average head size, short stature, clubbed feet, abnormalities of the genitals, and muscle weakness (hypotonia). About 85% of boys with Alpha-Thalassemia Intellectual Disability Syndrome also have a blood disorder called Alpha-Thalassemia, a type of anaemia. Although some children with this condition are less severely affected than others, most need lifelong medical treatment.

    Female carriers for Alpha-Thalassemia Intellectual Disability Syndrome typically do not have any symptoms. However, there are rare female carriers who have mild anaemia or intellectual disability.

     

    What causes Alpha-Thalassemia Intellectual Disability Syndrome?

    Alpha-Thalassemia Intellectual Disability Syndrome is caused by a change, or mutation, in the ATRX gene. This mutation causes the gene to not work properly or not work at all, which results in the symptoms described above. 

     

    Carrier rates < 1 in 500; Detection rates 49%; Residual risk 1 in 979

     

     

  • X-liiteline Alporti sündroom

    What is Alport Syndrome, X-Linked?

     

    Alport Syndrome, X-Linked is an X-linked inherited condition that affects the kidneys, ears, and eyes. Alport Syndrome, X-Linked causes progressive loss of kidney function which leads to blood and protein in the urine. Over time, the kidneys can no longer work properly and dialysis or kidney transplant is often needed, typically in early to late adulthood. Sensorineural hearing loss usually occurs in late childhood or early teens, but hearing aids are typically effective. Eye problems include increased risk for cataracts, abnormally shaped lenses, and wearing away of the cornea. People with Alport Syndrome, X-Linked often need glasses, but it is rare for them to have vision loss.  Alport Syndrome, X-Linked is more common in boys than girls. 

     

    What causes Alport Syndrome, X-Linked?

     

    Alport Syndrome, X-Linked is caused by a change, or mutation, in the COL4A5 gene. This mutation causes the gene to not work properly or not work at all.  The normal function of the COL4A5 gene is to help make Type IV collagen. Type IV collagen is needed in the kidney, inner ear, and eye in order for these organs to work properly.   When the COL4A5 gene is not working correctly in a male, it leads to the symptoms described above. Some female carriers may have clinical symptoms associated with Alport Syndrome, X-Linked such as blood in the urine, which is common in carriers, or kidney disease or hearing loss, which are less common.

     

    Carrier rates < 1 in 500; Detection rates 83%; Residual risk 1 in 2396

     

     

 

X- liiteliselt päranduvate haiguste nimekiri on valmimisel

 

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