31. Congenital Malformations and Their Causes

  1. Anomalies of development
    1. ETIOLOGIC FACTORS: malformations develop as a result of 3 mechanisms
      1. Noxious influence of external factors during the first phase of development. This type of teratogenic agent has been studied experimentally
      2. Transmission of a genetic abnormality by the parents: is inscribed in the genetic code of one or both parents and transmitted according to the laws of heredity
        1. The fetus may be the carrier of a purely molecular abnormality, such as hemophilia, due to the absence of a globulin necessary for coagulation
        2. This molecular abnormality also may be translated on the cellular scale: an abnormal hemoglobin can bring about a visible RBC deformity

        3. More rarely, certain metabolic anomalies bring about a morphologically visible malformation, such as the dwarfism and body deformities of achondroplasia
        4. Chromosome aberration existing in one of the gametes or appearing during the first division
          1. The mechanism can result in an abnormality of chromosome constitution at the time of gametogenesis
          2. At fertilization, the zygote resulting from the above gamete will have an abnormal karyotype which will be transmitted to all cells of the embryo. Thus, the abnormality can involve either an autosome or a sex chromosome
      1. The most frequent is mongolism or Down's syndrome which is caused by trisomy 21; that is, chromosome pair 21 consists of 3 chromosomes instead of One gamete, the ovum (most frequently abnormal) carries two 21 chromosomes, whereas the other, the spermatozoon, normally carries only on The zygote thus contains three 21 chromosomes and 47 chromosomes in total
        1. Characteristics: mental deficiency, brachycephaly, flat nasal bridge; slant to eyelid fissures; protruding tongue, simian crease, congenital heart defects
      2. Trisomy 17-18 results in mental retardation, congenital heart defects, low-set ears, and flexion of the fingers and hands
        1. Frequently see micrognathia, renal anomalies, syndactyly, and skeletal malformations
        2. Seen in about 0.3 of 1000 births, and infants usually die by the age of 2 months
      3. Trisomy 13-15 results in mental retardation, congenital heart defects, deafness, and cleft lip and palat Also shows microphthalmia, anophthalmia, and coloboma
        1. Incidence is about 0.2 per 10,000 newborns. Most die by 3 months
      1. Appear to be more frequent than autosomal abnormalities, but this may be due to the fact that the latter usually lead to precocious death of the embryo
      2. Initiated by a chromosomal anomaly of the ovum; 2 major sex chromosome aberrations are described
        1. Turner's syndrome: the ovum does not carry any sex chromosome; there is a female phenotype (appearance), and one sees dwarfism, malformation, and gonadal aplasia or dysgenesis
        2. All cells are sex-chromatin negative, and cells have only 45 chromosomes with an XO chromosomal complement

          Usually due to nondisjunction in male gamete during meiosis

        3. Klinefelter's syndrome: the ovum carries 2 sex chromosomes; the phenotype is male, and one notes sterility, testicular atrophy, hyalinization of the seminiferous tubules, and usually gynecomastia
        4. Cells have 47 chromosomes with a sex chromosomal complement of XXY type, and a sex chromatin body is seen in 80% of cases

          Seen in 1 of 500 male births; caused by nondisjunction of the XX homologs

        5. Triple-X syndrome: from fertilization of an XX oocyte by an X sperm
        6. Patients are infantile with scanty menses and a degree of mental retardation

          Have 2 sex chromatin bodies in their cells and are called "superfemale"

          Some are of proven fertility, and offspring may be normal

congenital malformations and  their causes: image #1