In-je University College of Medicine 출산 결함 2017. 06. 02 Department of Anatomy In-je University College of Medicine

Congenital malformation Birth defect Congenital anomaly Congenital malformation 구조적, 기능적, 대사성, 행동적, 유전적인 면에 있어서의 결함 국제질병분류 (International Classification of Diseases; WHO 1975)

Cause of congenital anomalies Incidence : 2- 5 % of newborn (USA ; 3%) 8% by age 5 Perinatal deaths : 20 %

Type of congenital anomalies Malformation : by abnormal primordium (내인성 이상형성) Disruption : by external factor (외인성 이상형성) Deformation : by mechanical factor (형태, 위치의 이상) Dysplasia : by abnormal histogenesis (조직구성수준의 장애) partial or complete alterations in the normal structure. occurs in the 3rd to the 8th week of gestation. Ex) Cleft lip, cleft palate. morphological change of the already formed structure due to exposure to destructive process (; teratogen). Ex) Vascular accidents  bowel atresias affect a part of the fetus over a long period. Ex) talipes equinovarus deformity

Congenital anomaly by genetic factors 1. Numerical Chromosomal abnormalities 2. Structural chromosomal abnormalities 3. Anomalies caused by mutant genes

1. Numerical Chromosomal abnormalities The normal human cell ; 46 chromosomes - 44 autosomes - 2 sex chromosomes (XX or XY) 1. Monosomy (45 chromosomes): (Ex) Turner syndrome (44X): 1/8000 birth Absent 2nd X chromosome. Short stature Lack of ovarian development Webbed neck Arms that turn out slightly at the elbow Low hairline

2. Trisomy (47 chromosomes): It is due to meiotic nondisjunction of chromosomes resulting in a gamete with 24 instead of 23 chromosomes and subsequently in a zygote with 47 chromosomes. It may affect sex chromosomes or autosomes. (Ex) Down syndrome (trisomy 21) Edwards syndrome (trisomy 18) Patau syndrom (trisomy 13) : 1/800 birth : 1/8000 birth : 1/25000 birth

Down syndrome : trisomy 21 oblique eye fissures with small skin folds on the inner corner of the eyes. muscle hypotonia, a flat nasal bridge, a single palmar fold, a large and protruding tongue, a short neck, white spots on the iris. congenital heart defects, excessive space between large and second toe, and a single flexion furrow of the fifth finger. mental retardation

Edwards syndrome (trisomy 18) Clenched hands with overlapping fingers. The fifth finger lies on top of the fourth finger while the third finger is overlapped by the index finger. Delays in development and growth A disorder of the muscle that leads to several joint contractures A small head

Patau syndrom (trisomy 13) ; note cleft lip & palate, polydactyly (excess finger), umbilical hernia

Sex chromosome XXX : super female syndrome XXY : Klinefelters syndrome (1/960 birth) XXY : Klinefelters syndrome (1/1080 birth) Patients with triple X are infantile Scanty menses Some degree of mental retardation

3) Tetrasomy & pentasomy of sex chromosomes: In females : 48(44,XXXX) & 49(44,XXXXX). In males : 48(44,XXXY, 48(44,XXYY), 49(44,XXXXY) & 49(44,XXXYY). pentasomy

2. Structural chromosomal abnormalities It results from chromosome break down followed by reconstitution in abnormal combination: Translocation: 염색체의 일부분이 비상동 염색체로 이동 Deletion: 염색체의 일부분 소실 Duplication Inversion Isochromosome 5

3. Anomalies caused by mutant genes It result from permanent heritable changes in the sequence of genomic DNA (Ex) “achondroplasia (연골무형성증)” Short stature Short limbs, fingers & toes. Large head, with depressed nasal bridge & prominent forehead. Normal length of the trunk.

Congenital anomaly by Teratogenic (environmental) factors Infectious agents Radiation Chemical Agents Hormones Maternal Disease Nutritional Deficiencies Hypoxia

1. Drugs a) Alcohol: → Produces Fetal Alcohol Syndrome(FAS) For example a) Alcohol: → Produces Fetal Alcohol Syndrome(FAS) → the infant has: - Microcephaly - Narrow palpebral fissure - Mental & growth retardation. - Big tongue & depressed nasal bridge Facies: small eye openings and vision anomalies, drooping eyelids, short upturned nose, sunken nasal bridge, low-set or underformed ears

b) Thalidomide: c) Androgens: Produces limb defects as Meromelia (small limb) & Amelia (absent limb). c) Androgens: They affect female fetus producing masculinization of the external genitalia resulting in: Enlarged clitoris, Fused labia majora Meromelia Labia majora Clitoris

2. Infectious agents Cataract Glaucoma a) Viruses: - Rubella (German measles) virus may result in congenital cataract or glaucoma - Herpes simplex & human HIV b) Bacteria: (Ex) spirochetes may cause congenital syphilis c) Parasites: (Ex) toxoplasmosis Spirochetes Toxoplasmosis

3. 기타 3) Chemicals: Heavy metals (Ex. methyl mercury) → cerebral atrophy & mental retardation. 4) High level of ionizing radiation: → microcephaly & mental retardation. 5) Maternal diseases: (Ex) diabetes mellitus 6) Antibiotics ; tetracycline, streptomycin 7) Radiation

출생시 기관별 주요 이상 빈도

사람발생에 있어 결정적 시기

Critical period