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KONSELING GENETIK
M. Mansyur RomiBag. Anatomi, Embriologi & Antropologi FK UGM
Tim Genetika Klinik RSUP DR.SARDJITO YOGYAKARTA
Pertanyaan klasik: ? Kelamin janin ? ? Janin normal ?
Peralatan lama: Variabel ukuran uterus Kenaikan BB ibu Auskultasi jantung janin
Peralatan abad XX 1950an: analisis sel janin dr cairan amnion
utk keberadaan sex chromatin 1966: kultur sel dr cairan amnion 1972: USG utk diagnosis anencephaly Saat ini USG mampu menilai hampir
seluruh anatomi janin
Penafsiran diagnosis pranatal bergantung:
Sampel yg dapat diperoleh Teknik yg dapat dipakai Informasi yg dapat diolah
Ragam sampel: Serum maternal, untuk:
Penanda (marker) cerminan kesehatan janin Protein yg berasal dr janin
Cairan amnion, untuk: Bahan yg dpt dianalisis (analytes) Sel yg berasal dr janin
Villus chorion, untuk: sel trofoblast Sel darah janin: eritrosit & lekosit
Teknik yg dipakai
Sampling darah maternal Amniocentesis Chorionic villous sampling (CVS) Cordocentesis Ultrasonography (USG) Embryo biopsy
Penapisan (screening) serum maternal Alfa fetoprotein (AFP)
Produksi dlm hepar janin, puncak: mgg 10-13 Dlm darah maternal lewat placenta atau difusi
menembus membran Konsentrasi puncak : mgg 24-32
Some causes of increased maternal serum AFP concentration Undersestimated gestational age Threatened abortion Multiple pregnancy Fetal abnormality: anencephaly, open neural tube
defect, anterior abdominal wall defect, Turner’s syndrome, bowel atresias, skin defects
Placental hemangioma
Decreased matenal serum AFP concentration: Trisomy 21, 18
Triple screen: AFP Human chorionic gonadotropin (HCG)
Disekresi embryo baru implantasi Unconjugated estrogen (UE)
Amniocentesis Cairan amnion volume> dg usia: 15-350
ml berisi: urin janin + bahan maternal normal steril dan tahan infeksi perlakuan umumnya pd trimester dua dg
risiko kematian janin 0,5 % perlakuan dini: mgg 12-15 dg risiko 2-11%
amniocentesis
Indikasi Analisis kromosom dari sel amnion yang
dikultur: trisomi 21 dsb Estimasi konsentrasi AFP dan aktifitas
acetylcholin esterase (Ache): neural tube defects
Analisis biokimiawi cairan amnion dan sel kultur: inborn error of metabolism
CVS Sel trofoblas: cermin status genetik janin cepat berproliferasi, tak perlu kultur sumber utk:
karyotype pemeriksaan DNA pengukuran aktifitas enzim yg diekspresi derivat
fibroblast perlakuan mgg 9-11 dg risiko kematian janin 2-
13%
Chorionic Villus Sampling (CVS)
Indication for CVS Diagnosis of chromosomal disorders Increasing number of inborn error of
metabolism DNA analysis
Cordocentesis Dilakukan bila cara lain utk mdpt sel janin
takcukup atau serum fetal sangat perlu dikaji sel janin utk: karyotyping bila dg cara lain
tampak mosaicism darah janin utk: mengukur protein serum hanya di pusat sangat khusus, risiko kematian
janin 0-3%
USG
Informasi anatomis dan fungsional janin mengungkap struktur: kepala, thorax,
abdomen, skeleton dan pertumbuhan janin real time usg: struktur & aktifitas jantung modern usg utk rincian anatomi janin:
ukuran & posisi ruang jantung, ventriculus cerebri, aorta & a.pulmonalis
MENGAPA PERLU MEMPELAJARI GENETIKA? Pergeseran pola : penyakit ‘lingkungan
‘(malnutrisi & infeksi) menurun, penyakit degeneratif & genetik meningkat
Terungkapnya peran faktor genetik sebagai penyebab penyakit pada manusia
Turunnya angka kematian bayi: Indonesia: 142%o(71)67%o(91),DIY:62%o(‘80)26%o(‘92)15,5%o(‘00)
Meluasnya konsep keluarga kecil
Genetically determined diseases Chromosomal disorders Single gene disorders Polygenic or multifactorial diseases Somatic cell genetic disorders
Mitochondrial genetic disorders
RAGAM PENYAKIT GENETIKKELAINAN KROMOSOMAL Pada umumnya jarang Pola pewarisan tidak jelas Biasanya resiko kerabat rendah
KELAINAN GEN TUNGGAL/MONOGENIK Jumlah ragamnya banyak, masing-masing kasusnya sedikit Pola pewarisan jelas, ikuti hukum Mendel Resiko kerabat tinggi
PENYAKIT POLIGENIK/MULTIFAKTORIAL Banyak dijumpai Pola pewarisan tidak jelas Resiko kerabat rendah-sedang
KELAINAN MUTASI SEL SOMATIK Mungkin ada gambaran “mosaik” Menyebabkan neoplasia/keganasan
KELAINAN GEN MITOKHONDRIA Pola pewarisan”maternal”atau sporadic
Coiling of DNA
Incidence of some common single gene disorders (Seashore & Weppner, 1996)
Single gene disorder Incidence
HypercholesterolemiaSickle cell anemiaCystic fibrosisTay-Sachs diseaseHuntington dssPhenylketonuria
1 in 5001 in 600 (african ansestry)1 in 1600 (european anst1 in 3500 (ashkenazi jew1 in 50001 in 10.000
Common conditions that are gene-influenced (Seashore & Weppner, 1996)
Childhood Adulthood
Cleft lip and palateSpina bifidaCongenital heart dssJuvenile diabetes mellCancerPyloric stenosis
Coronary artery dssDiabetes mellitusSchizophreniaHypertensionCancerAlcoholism
Features of medical history that raise genetic concerns (Seashore & Weppner, 1996)
Feature Risk
Multiple affected family members
Single gene; multifactorial; chromosomal
Family history of known inherited disorder
Risk of being affected with same condition
Maternal age over 35 yrs at delivery
Chromosome abnormality in baby
Genetic components of childhood mortality in the UK (Gelehrter et al. 1998)
Cause of death Newcastle London
ChromosomalSingle genePolygenicNongenetic/unknown
Total deaths
2.5% 8.5% 31.0% 58.0%
1041
}12.0%
25.5% 62.5%
200
Frequency of genetic disorders among pediatric Hospital Admissions in North America (Gelehrter et al. 1998)
Cause Seattle Montreal
ChromosomalSingle genePolygenicNongenetic
No. of admissions
0.6% 3.9% 48.9% 46.9%
4,115
0.4% 6.9% 29.0% 63.7%
12,801
Suggested readings: Gelehrter TD, Collins FS, Ginsburg D. Principles of
Medical Genetics 2nd ed. Williams & Wilkins 1998 Mange AP, Mange EJ. Genetics: Human Aspects 2nd ed.
Sinauer Assoc. Inc. 1990 Seashore MR, Wappner RS. Genetics in Primary Care &
Clinical Medicine. Prentice-Hall 1996 Kingston HM. ABC of Clinical Genetics BMJ 1994 Hartono, Risanto, Suryadi E, Romi MM. Buku Genetika
Kedokteran, FK UGM 2004