1.

Apa itu kelainan kongenital

2. Macam kelainan kongenital
3. Penyebab kelainan kongenital
4. Langkah prevensi kelainan kongenital
5. Factor risiko kelainan kongenital
6. Pathogenesis, gejala klinis terjadiny kelainan
kongenital

Congenital defect: abnormalitas pada struktur badan,

fungsi, metabolisme yang ikutan hadir saat kelahiran.

Caused?
Factor genetic (warisan single-gene atau multifactorial
atau penyimpangan kromosom)
Factor lingkungan saat perkembangan embrionik maupun
fetal (penyakit maternal, infeksi, atau yg dikonsumsi selama
kehamilan)

GENETIC AND CHROMOSOMAL DISORDERS

Genetic disorder? Serangkaian kejadian yg memengaruhi

ekspresi gen dalam suatu sel yang berhubungan satu
dengan lain dengan gene linkage (keterkaitan gen).
Caused? Perubahan pada rangkai DNA yang mengubah
sintesis pada produk gen nya.
What involve genetic disorder? Sifat single-gene, warisan
multifactorial, abnormalitas kromosom, mitochondrial gene
disorder.

PENTING!
genes on each chromosome are arranged in pairs and in
strict order, with each gene occupying a specific location
or locus.
The two members of a gene pair, one inherited from the
mother and the other from the father, are called alleles.
If the members of a gene pair are identical (i.e., code the
exact same gene product), the person is homozygous, and Autosomal dominant disorder? satu alel mutant tunggal dari
if the two members are different, the person is orangtua yang terkena dampak tertransmisi ke keturunan.
heterozygous. The genetic composition of a person is called Autosomal recessive disorder? Both members dari gen
a genotype, whereas the phenotype is the observable affected (terkena dampak). Dalam case ini, kedua parents
expression of a genotype in terms of morphologic, mungkin unaffected tapi carrier.
biochemical, or molecular traits. If the trait is expressed in
the heterozygote (one member of the gene pair codes for
the trait), it is said to be dominant. If it is expressed only in
the homozygote (both members of the gene pair code for
the trait), it is recessive.

Single-gene Disorder
Caused? Defective(cacat) atau mutant allele at a single
locus and follow mendelian patterns of inheritance.
Karakter? Pattern transmisinya itu biasanya diperoleh
through a family genetic history.
Impact? All single-gene disorder mengakibatkan
pembentukan protein abnormal atau penurunan produksi
produk gen.
Bisa juga mengakibatkan defective enzim atau penurunan
jumlah enzim, defect di reseptor protein dan fungsinya,
alterations in nonenzyme protein, ato mutasi yang
menghasilkan reaksi tidak biasa pada drugs.
X-Linked recessive disorder? Selalu berhubungan sama Numeric Disorders Involving Autosomes? Abnormal number
kromosom X dan pattern warisannya itu predominantly of kromosom disebut aneuploidy.
recessive. Makanya pada perempuan jarang timbul efek dari Caused? Kromosom gagal berpisah saat oogenis atau
kecacatan gen ini, berbanding terbalik sama cowo yang spermatogenesis. (monosomy,polysomy)
pasti kena dampaknya.
Fragile X syndrome? Is a single-gene disorder yang
menyebabkan disabilitas intelektual.
Terjadi lebih banyak di cowo daripada cewe.

Multifactorial Inheritance Disorder Numeric Disorders Involving Sex Chromosomes? Lebih

Caused? Multiple gene, di kasus lain factor lingkungan.
Cases ex.? Cleft lip or palate, clubfoot, congenital disorder
of hip, congenital heart disease, pyloric stenosis
Enviromental factor? Develop in adult life. Mis coronary
artery disesase, DM, hipertensi, kanker.
Characteristic patterns?
1.Tend to involve a single organ atau jaringan yang berasal
dari embryonic developmental field yang sama.
2. the risk of recurrence in future pregnancies is for the
same or a similar defect. This means that parents of a child
with a cleft palate defect have an increased risk of having
another child with a cleft palate, but not with spina bifida.
3. The risk increases with increasing incidence of the
defect among relatives. This means that the risk is greatly
increased when a second child with the defect is born to a
couple. The risk also increases with severity of the disorder
and when the defect occurs in the sex not usually affected
by the disorder.
umum terjadi daripada yang autosomes, kecuali buat
trisomy 21.
Caused?
1. The inactivation of all but one X chromosome
2. The modest amount of genetic material that is carried on
the Y chromosome
Mitochondrial Gene Disorders
The mitochondria contain their own DNA, which is distinct
from the DNA contained in the cell nucleus. There are mul-
tiple disease-affected rearrangements and point mutations.
Mitochondrial DNA (mtDNA) is packaged in doublestranded
circular chromosome located inside the mitochondria. In
contrast to the mendelian pattern of inheritance of nuclear
DNA, disorders of mtDNA are inherited on the mater- nal
line. This can be explained by the fact that ova contain
numerous mitochondria in their abundant cytoplasm,
whereas spermatozoa contain few, if any, mitochondria.

Chromosomal Disorders
Impact? large proportion of reproductive wast- age (early
gestational abortions), congenital malformations, and
intellectual disability.

Structural chromosomal abnormalities? Terjadi karena

breakage in one or more kromosom dan diikuti
rearengement or deletion chromosome parts.
Caused? Yg dipercaya itu exposure to radiation sources
(xrays), pengaruh chemical tertentu, extreme changes in
the cellular environment, viral infections.
 Teratogenic terbagi into 3 groups: radiasi, drugs and
chemical substance, and agen infeksius.
How TA cause birth defect?
1. By direct exposure of the pregnant woman and the
embryo or fetus to the agent
2. Through exposure of the soon-to-be-pregnant woman
to an agent that has a slow clearance rate, such that a
teratogenic dose is retained during early pregnancy
3. As a result of mutagenic effects of an environmental
agent that occur before pregnancy, causing permanent
damage to a woman’s (or a man’s) reproductive cells

Radiation
Dosis besar dari radiasi pengion adalah teratogenic dan
mutagenic dan punya kapasitas untuk menyebabkan
perubahaan inheritable (bawaan) pada material genetic.
Cases ex.? Microcephaly, malformasi skeletal, mental
retardation

Chemicals and Drugs

CnB can cross placenta terus casue damage to the
developing fetus or embryo.

Infectious Agents
Mikroorganisme yang cross placenta and enter fetal
circulation. TORCH (toxoplasma, other, rubella,
cytomegalovirus, herpes) paling sering menyebabkan fetal
anomaly.
Selain itu bisa juga varicella-zoster, HIV, tbc, sifilis.

FOLIC ACID DEFICIENCY

Kekurangan asam folat yang bisa menyebabkan NTD (neural
tube defect) (e.g anencephaly, spina bifida, encephalocele)

LANGKAH PREVENSI KELAINAN KONGENITAL

DISORDERS DUE TO ENVIRO INFLUENCES
Periode Kerentanan
Paling rentan saat organogenesis (15-60 day after
konsepsi).
Agen Teratogenik
Chemical, physical, or biologic agent that produces
abnormalities during embrionik atau fetal development.
1. Genetic Assesment
genetic counseling involves accurate. diagnosis and
communication of the. findings and of the risks of
recurrence.
2. Prenatal Screening&Diagnosis
The purpose of prenatal screening and diagnosis is not
just to detect fetal abnormalities but also to allay
anxiety and pro- vide assistance to prepare for a child
with a specific disability.
There are multiple methods that can assist in
diagnosing a fetus regarding genetic disorders,
including ultrasonography, maternal serum (blood)
screening tests, amniocentesis, chorionic villus
 sampling, and percutaneous umbilical fetal blood
sampling

STEP 1
Stillbirths: baby born with no signs of life at or after 28 weeks'
gestation. (From who)
MALFORMASI: suatu tipe anomali. Defect morfologik suatu organ
tau bag tubuh yg lebih besar, yg diakibatkan oleh kelainan process
perkembangan intrinsik. (Kamus dorland)
Dysplasia: kelainan perkembangan. Dlm patologi: perubahan
ukuran, bentuk dan susunan sel-sel devasa.
Deformation: dalam dismorfologi, suatu jenis defek struktural yg
ditandai dgn bentuk atau posisi yg abnormal dari suatu bag tubuh,
disebabkan o kekuatan mekanis yg tidak terputus2. Proses
mengadaptasi bentuk.
Disruption: defek morfologik yg diakibatkan o kerusakan extrinsic
atau ggn pd proses perkembangan.
Congenital: tjd saat lahir atau biasanya sblm lahir; merujuk pd
kondisi2 yg ditemukan saat lahir, tanpa memandang penyebab.
Pathogenesis: perkembangan keaadaan sakit ato penyakit; lbh
khusus lagi, rx dan peristirwa selular serta mekanisme patologis
yg tjd dalam perkembangan penyakit.
Vector: carrier, khususnya hewan yg nularin agen infektif; cloning,
molekul dna yg dpt membawa fragmen dna asing ke dlm sel hopses
dan nyipatain banyak copy.